P2830Clinical and genetic findings in relatives to young sudden cardiac death victims without post-mortem examination (autopsy)

Abstract Background Guidelines recommend clinical assessment of relatives to young sudden cardiac death (SCD) victims (<50 years) to protect the surviving relatives by pre-symptomatic interventions, in case the SCD was due to an inherited cardiac disorder. The etiology is an inherited cardiac disease in about 50% of young SCD cases. The work-up of relatives is generally guided by findings in the SCD victim. If post-mortem examinations (autopsies) have not been performed the work-up of relatives is challenged. The diagnostic hit-ratio of screening of relatives under these circumstances is unclear. Purpose To assess the diagnostic yield of inherited cardiac diseases of cardiac work-up in relatives of SCD victims, where no autopsy had been performed. Methods This retrospective study consecutively included families referred to our tertiary referral centre, specialised in hereditary cardiac diseases, during the period 2005 to 2018 due to SCD in the family. No autopsy had been performed in any of the SCD victims. The relatives underwent standard cardiac work-up according to guidelines. Based on the findings in the relatives the families were categorised into: 1) definite diagnosis, 2) borderline diagnosis or 3) undiagnosed. Results We assessed 149 relatives (43±16 age, 48% men) to 84 SCD un-autopsied cases (44±11 age, 79% men). In 11 (13%) families a definite diagnosis was established, in 8 (10%) families a borderline diagnosis was found and the remaining 65 (77%) families remained undiagnosed. The most common diagnosis was premature IHD (36%) followed by cardiomyopathies (27%) and channelopathies (27%). A disease-causing mutation was identified in 3 families out of 15 genetically examined families. Conclusion Systematic cardiac work-up of relatives to not-autopsied SCD victims, revealed a definite hereditary cardiac disease in 13% of the referred families, and a borderline diagnosis in additionally 10% of the families. Despite a reduced diagnostic yield in family members of non-autopsied SCD victims, work-up of relatives is clearly still justified.

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P5026Diagnostic yield in victims of sudden cardiac death and their relatives

European Heart Journal ◽

10.1093/eurheartj/ehz746.0204 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

B L Hansen ◽

E M Jacobsen ◽

A Kjerrumgaard ◽

B G Winkel ◽

A C Christensen ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Cardiac Disease ◽

Cardiac Death ◽

Diagnostic Yield ◽

Family Screening ◽

Screening Protocol ◽

Borderline Diagnosis ◽

Cardiac Diagnosis ◽

Work Up ◽

Inherited Cardiac Disease

Abstract Background International guidelines recommend screening of relatives in families with sudden cardiac death (SCD) if the cause of death is suspected to be an inheritable cardiac disease. The inheritable cardiac diagnosis may either have been known before the death, established at the autopsy or identified through screening of relatives. Purpose To provide an estimate of the diagnostic yield of inherited cardiac disease in SCD victims. Methods In an observational study, we included all families consecutively referred to our tertiary unit for inheritable cardiac diseases in the period from 2005 to 2018 due to SCD. Families with SCD victims under 1 year of age were excluded. In total, 697 relatives from 305 families were included and all relatives underwent a standard screening protocol, which included clinical and genetic work-up. Premortem medical records and postmortem findings on the SCD victim were ascertained whenever possible. Results A definite inheritable cardiac disease was identified in 113 out of 305 SCD families prior to family screening. The diagnosis was established through autopsy findings (n=89), genetic analysis (n=3) or was established prior to death (n=21). In the remaining 192 families with no or a borderline diagnosis only, screening of the relatives yielded a diagnosis in additional 28 families (15%). On a family-basis, a total of 141 out of 305 families (46%) were diagnosed. Seventy-seven (11%) out of the 697 screened relatives received either a phenotype-positive and/or genotype-positive inheritable diagnosis and 70 (10%) relatives received a borderline diagnosis. The most common diagnoses in the relatives were ARVC (n=17) followed by DCM (n=10) (see figure). Conclusion Almost half of SCD families were diagnosed with an inheritable cardiac disease of which one fifth of the families were diagnosed as a result of family screening. In 11% of the screened relatives a probable inheritable diagnosis was identified.

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Diagnostic yield in victims of sudden cardiac death and their relatives

EP Europace ◽

10.1093/europace/euaa056 ◽

2020 ◽

Vol 22 (6) ◽

pp. 964-971 ◽

Cited By ~ 2

Author(s):

Benjamin Lautrup Hansen ◽

Elisabeth Mütze Jacobsen ◽

Amalie Kjerrumgaard ◽

Jacob Tfelt-Hansen ◽

Bo Gregers Winkel ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Cardiac Disease ◽

Cardiac Death ◽

Cardiovascular Events ◽

Diagnostic Yield ◽

Arrhythmogenic Right Ventricular Cardiomyopathy ◽

Cardiac Events ◽

Common Diagnosis ◽

Inherited Cardiac Disease ◽

Low Rate

Abstract Aims International guidelines recommend cardiogenetic screening in families with sudden cardiac death (SCD) if the suspected cause is an inherited cardiac disease. The aim was to assess the diagnostic yield of inherited cardiac diseases in consecutively referred SCD families. Methods and results In this single-centre retrospective study, we consecutively included families referred to our tertiary unit between 2005 and 2018 for screening due to SCD. Following evaluation of premortem medical records and postmortem findings for the proband, the families underwent a guideline-based screening protocol. Relatives were followed and cardiovascular events registered. In total, 304 families with 695 relatives were included. In probands, mean age at death was 39 years (75% males) and in relatives mean age at screening was 35 years (47% males). The proband-diagnosis was established through autopsy findings (n = 89), genetic analyses (n = 7), or based on premortem findings (n = 21). In the remaining 187 families with borderline/no diagnosis in the proband, screening of relatives yielded a diagnosis in 26 additional families. In total, an inherited cardiac disease was identified in 143 out of 304 families (47%). In relatives, 73 (11%) were diagnosed. Arrhythmogenic right ventricular cardiomyopathy (n = 16) was the most common diagnosis. During follow-up (mean 5.5 years), a low rate of serious cardiac events was observed (no SCD events). Conclusion Forty-seven percent of SCD families were diagnosed. Eleven percent of the screened relatives received a definite diagnosis and were offered treatment according to guidelines. A low rate of serious cardiovascular events was observed among SCD relatives.

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P2821Diagnostic yield and outcomes of systematic work-up of aborted sudden cardiac death victims and their relatives

European Heart Journal ◽

10.1093/eurheartj/ehz748.1131 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

E Muetze Jacobsen ◽

A J Kjerrumgaard ◽

B L Hansen ◽

B G Winkel ◽

A H Christensen ◽

...

Keyword(s):

Cardiac Arrest ◽

Cardiac Disease ◽

Cardiac Diseases ◽

Tertiary Referral ◽

Systematic Screening ◽

Tertiary Referral Center ◽

Cardiac Disorder ◽

Screening Protocol ◽

Borderline Diagnosis ◽

Work Up

Abstract Introduction Cardiac arrest can be the first manifestation of most inherited cardiac diseases. This motivates the international guidelines recommending screening of relatives of cardiac arrest survivors (aSCD) if an inherited cardiac disorder might have caused the cardiac arrest. Purpose To assess the presence of inheritable cardiac diseases in cardiac arrest survivors and their relatives. Methods In this retrospective study we consecutively included cardiac arrest survivors (probands) and their relatives referred to our tertiary referral center from 2005 to 2018. All probands and relatives underwent a systematic screening protocol. Data were retrieved from medical files. Only probands with non-ischemic heart disease were included. Results We included 155 probands (41±16 years old, 94 (61%) male) and 284 relatives (36±19 years old, 144 (51%) male). We identified an inheritable cardiac disease in 70 (45%) probands, most frequently cardiomyopathies (41, 26%) followed by channelopathies (27, 17%) (figure). A borderline diagnosis was found in 32 (21%) probands. In the relatives, an inheritable diagnosis was identified in 38 (13%) individuals, most frequently channelopathies (23, 8%), and a borderline diagnosis was identified in 33 (12%) individuals. Conclusion Clinical assessment of aSCD cases on a non-ischemic basis identified an inheritable cardiac disease as the most likely etiology in almost half of the probands and in 13% of the relatives.

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Diagnostic findings in relatives to victims of sudden unexplained death or non-autopsied possible sudden cardiac death

European Heart Journal ◽

10.1093/ehjci/ehaa946.3632 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

C.V Dalgaard ◽

B.L Hansen ◽

E.M Jacobsen ◽

A Kjerrumgaard ◽

J Tfelt-Hansen ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Cardiac Disease ◽

Cardiac Death ◽

Diagnostic Yield ◽

Initial Evaluation ◽

Funding Source ◽

Sudden Unexplained Death ◽

Unexplained Death ◽

Inherited Cardiac Disease

Abstract Introduction Sudden cardiac death (SCD) may be caused by several inherited cardiac diseases and screening and treatment of relatives may be lifesaving. Sudden unexplained death (SUD) victims have been autopsied, whereas non-autopsied possible SCD (pSCD) victims are only filtered on manner of death and medical records. Screening of relatives may identify an inherited cardiac disease. Purpose To assess the diagnostic yield at initial evaluation and during follow-up of relatives to SUD and pSCD victims. Furthermore, to evaluate the outcome in the relatives. Methods We retrospectively included first-degree relatives to SUD and pSCD victims referred to our tertiary center from 2005 to 2018. Probands with known antemortem inherited cardiac disease were excluded. Data from systematic screening and routine follow-up of the relatives were registered. Results We included 371 first-degree relatives from 187 families: 276 SUD relatives (age at initial evaluation 35±17 years, 54% men;) and 95 pSCD relatives (age at initial evaluation 40±15 years, 51% men). The diagnostic yield among SUD families was 18%, among pSCD families 13% (p>0.05 between groups). The diagnoses in SUD families were mainly channelopathies (68%), whereas the pSCD families were diagnosed with cardiomyopathies, channelopathies, and premature ischemic heart disease (Figure 1). The vast majority of diagnosed families (93%) were diagnosed at the initial evaluation and only two families were diagnosed during the mean follow-up of 5.4 years. During follow-up, 57 (15%) relatives had a cardiac-related hospitalization, 12 (3%) relatives had a cardiac device implanted, three (1%) relatives died of non-cardiac causes, and one (0.5%) relative had a myocardial infarction. There was no significant difference in cardiac event rates between the SUD and pSCD groups (all p>0.05). Conclusion One in 6–7 families with SUD or pSCD victims obtained a diagnosis based on screening of relatives; we mainly diagnosed channelopathies in SUD families and a broader spectrum of inherited cardiac disease in the pSCD families. The majority of affected relatives was diagnosed at the initial evaluation and clinical follow-up may not be warranted in all relatives with normal findings at initial screening. Figure 1. Family diagnoses in categories, n (%) Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): The Capital Regions Research Foundation and The A.P. Moeller Foundation.

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Sudden Cardiac Death not Related to Coronary Atherosclerosis

Toxicologic Pathology ◽

10.1080/01926230500519824 ◽

2006 ◽

Vol 34 (1) ◽

pp. 52-57 ◽

Cited By ~ 13

Author(s):

Elena Ladich ◽

Renu Virmani ◽

Allen Burke

Keyword(s):

United States ◽

Cardiovascular Diseases ◽

Sudden Cardiac Death ◽

Cardiac Disease ◽

Cardiac Death ◽

Coronary Atherosclerosis ◽

The United States ◽

Cardiac Diseases ◽

Cardiac Events ◽

Myocardial Diseases

Sudden cardiac death (SCD) accounts for approximately 300,000 cardiac events in the United States each year, representing an overall incidence of 0.1–0.2% per year. Although the vast majority of these may be attributed to coronary atherosclerosis, a wide variety of nonatherosclerotic-related cardiac diseases have been associated with SCD. This review highlights three general categories of cardiac disease not related to atherosclerosis: the cardiomyopathies, inflammatory myocardial diseases, and ion channel disorders. The important role played by genetics in some of these cardiovascular diseases is presented as well as toxic and drug-related etiologies.

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Postmortem Specificity of Troponin for Acute Miocard Infarction Diagnosis throug Qualitative Dosing from Pericardial Fluid

Revista de Chimie ◽

10.37358/rc.18.9.6559 ◽

2018 ◽

Vol 69 (9) ◽

pp. 2482-2486

Author(s):

Iuliana Hunea ◽

Simona Irina Damian ◽

Carmen Corina Radu ◽

Sorin Moldoveanu ◽

Tatiana Iov

Keyword(s):

Sudden Cardiac Death ◽

Cardiac Disease ◽

Cardiac Death ◽

Troponin I ◽

Troponin T ◽

Morphological Changes ◽

Pericardial Fluid ◽

Histological Changes ◽

Lethal Arrhythmia ◽

Myocardial Lesions

Cardiac disease is the leading cause of death, and sudden cardiac death occupies the first place in sudden deaths of natural causes. Sudden cardiac death due to lethal arrhythmia may be the first manifestation of a cardiac disease, such cases becoming suspect dead, thus forensic cases. The autopsy performed in such cases may reveal important cardiovascular disease but not obvious macroscopic or histological changes of acute myocardial infarction (IMA), except for cases of survival for several hours after the onset of the symptomatology. Biochemical markers were used to test for myocardial lesions in the absence of morphological changes. Methods for determining myoglobin, CK-MB, troponin T (cTn T), troponin I (cTn I) were introduced to the clinic to diagnose the condition of patients with chest pain as early as the 1990s. The lack of pathognomonic elements in corps investigations, where part of the analysis cannot be carried out, requires verification of the value of the investigations that can be carried out, with reference to the biochemical in the present case, in establishing the diagnosis with certainty.

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Comparison of variant detection rate in genes between two cohorts of Czech living patients versus victims of sudden cardiac death with clinical / post mortem diagnosis of non-ischemic cardiomyopathy

European Heart Journal ◽

10.1093/ehjci/ehaa946.0338 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

E Borisincova ◽

P Votypka ◽

K Rucklova ◽

A Pilin ◽

M Kulvajtova ◽

...

Keyword(s):

At Risk ◽

Czech Republic ◽

Primary Prevention ◽

Sudden Cardiac Death ◽

Genetic Counselling ◽

Cardiac Death ◽

Detection Rate ◽

Funding Source ◽

Post Mortem ◽

Custom Made

Abstract Introduction Hereditary cardiomyopathy is associated with an increased risk of ventricular arrhythmia and sudden cardiac death (SCD). Genetic stratification substantiates risk assessment and enables the primary prevention of SCD in relatives at risk. We have analyzed the genetic aetiology of SCD in a representative Czech cohort with post mortem diagnosis of various forms of cardiomyopathy and compared it to living cases with these cardiac disorders. Patients and methods Between 2018 and 2019, altogether 47 victims of SCD with post mortem diagnosis of hypertrophic- (HCM; 18/47), arrhythmogenic- (ACM; 19/47) and dilated cardiomyopathy (DCM; 10/47) were identified. Concurrently, genetic testing was performed in 114 living patients (HCM 54/114, ACM 22/114, DCM 38/114). Genetic counselling and cardiologic examination had been carried out in first-degree relatives in all patients/SCD victims. Massively parallel sequencing (MiSeq platform; Illumina.com) was utilized for a custom-made panel comprising 100 candidate genes (Sophia Genetics, Switzerland). The presence of pathogenic variants was validated by Sanger DNA sequencing and through family segregation analyses. Results The causative detection rate (according to ACMG.net classes 4 or 5) in SCD victims with DCM was 60% (6/10) and in living patients with DCM 47.4% (18/38). Variants in TTN, RBM20, DES and FLNC (mainly truncating variants) prevailed in both groups. The detection rate in ACM was 5% (1/19 in SCN5A gene) in SCD victims and 31.8% (7/22) in living patients. Interestingly, the most prevalent mutated gene PKP2 in living patients was not detected in SCD victims. The detection rate in SCD victims with post mortem diagnosis of HCM was 16% (3/18) and in living patients 35% (19/54). The most prevalent gene was MYBPC3 in both groups, while PRKAG2 was detected in one SCD victim and in one living case who survived cardiac arrest. Conclusion Post-mortem genetic analysis in DCM yields a high detection rate and allows potentially effective primary prevention of SCD in relatives at risk. In contrast, the molecular autopsy of HCM and ACM renders a much lower yield which is below the mutation detection rate in living phenotype positive individuals. The results help to improve the genetic counselling in affected families in Czech Republic. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministry of Health of the Czech Republic

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