Ignite Creation Date:
2024-10-26 @ 3:42 PM
Last Modification Date:
2024-10-26 @ 3:42 PM
Study NCT ID:
NCT06642168
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-10-08
Brief Title:
Sudden Cardiac Arrest Related to Sport in Young and Value of the Genetic Assessment a French Prospective Register
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Registre Prospectif français Des Morts Subites Chez Des Sportifs Jeunes
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RESOUDRE
Brief Summary:
The increased risk of sudden cardiac arrest SCA or sudden cardiac death SCD related to vigorous physical activity is well-documented Currently for young victims under 35 years of SCASCD no etiology is found in 40 to 50 of cases after a standard medical assessment leading to two important consequences For the victims family it is difficult to understand and accept this tragic event and the risk of it occurring in another family member is a source of concern Medically the absence of a known cause limits the ability to effectively prevent such events
The RESOUDRE study will be a national prospective observational registry of young victims 12-35 years of sports-related SCASCD All cases will undergo the recommended etiological assessment including autopsy for SCA cases along with whole exome genetic analysis and toxicological testing In the event a genetic pathology is identified a genetic evaluation will be offered to other family members and appropriate medical care will be provided if necessary The results of this study could significantly reduce the number of unexplained sport-related SCASCD cases and aid in preventing these incidents among affected families
The RESOUDRE study will be a national prospective observational registry of young victims 12-35 years of sports-related SCASCD All cases will undergo the recommended etiological assessment including autopsy for SCA cases along with whole exome genetic analysis and toxicological testing In the event a genetic pathology is identified a genetic evaluation will be offered to other family members and appropriate medical care will be provided if necessary The results of this study could significantly reduce the number of unexplained sport-related SCASCD cases and aid in preventing these incidents among affected families
Detailed Description:
Background
The beneficial effects of moderate physical activity on health are well-established However it is also well-proven that intense sports participation increases the risk of cardiovascular events by 24 to 45 times before the age of 35 in individuals with known or unknown heart conditions Sudden cardiac arrest SCA sometimes leading to sudden cardiac death SCD is the most dramatic event linked to sports
Before the age of 35 sports-related SCASCD is rare occurring in 07 to 27 per 100000 athletes which amounts to approximately 80 cases per year according to two French prospective studies Despite its rarity these events are often traumatic and highly publicized presenting a significant public health and safety concern Non-traumatic sports-related SCASCD is primarily of cardiovascular origin irrespective of the level of sports participation In most cases SCA results from ventricular arrhythmia caused by known or undiagnosed arrhythmogenic cardiovascular disease which varies by the victims age After the age of 35 atheromatous coronary artery disease accounts for 80-85 of cases However before the age of 35 a wider range of etiologies are observed Arrhythmogenic genetic heart diseases-structural eg arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy or non-structural eg channelopathies-are the most frequent causes Congenital abnormalities particularly anomalous connection of coronary artery represent the second most common cause Acquired heart diseases such as fibrous scars mainly post-myocarditis and atheromatous coronary lesions are less frequently involved In this younger population classical autopsy often fails to determine the cause in more than 40 of cases leading to the term sudden arrhythmic syndrome
Few prospective studies have combined classical autopsy with systematic genetic analysis to identify the cause of SCASCD in the general young population with no specific link to sports One Australian study demonstrated the value of genetic testing identifying a clinically relevant cardiac genetic variant for sudden death in 27 of cases Moreover the same pathology was identified in 13 of relatives of the victims who underwent clinical and genetic screening Another small Swedish study n15 focusing specifically on channelopathies in cases of negative autopsies revealed the disease in 40 of victims families through genetic analysis
Additionally the role of acute or chronic toxic substance intake has been suggested albeit without formal proof as a factor promoting sports-related SCASCD Toxicological screening is thus recommended as part of the etiological assessment Including toxicological analysis alongside other etiological evaluations could help clarify the impact of illicit substances on sports-related SCASCD
Justifications for the Study
No prospective study has systematically combined the recommended hospital assessment in cases of successful resuscitation or the recommended medical autopsy in the event of death with global genetic and toxicological analyses in victims of sports-related SCASCD
This combined approach is justified for several reasons First it would enhance our understanding of the etiologies of these events Notably so-called idiopathic left ventricular hypertrophy is found in more than 10 of sports-related SCD cases following classical autopsies Further genetic exploration could help determine whether these anatomical forms are pathological Additionally many arrhythmic cardiac diseases are associated with an elevated risk of sports-related SCASCD While arrhythmogenic right ventricular cardiomyopathy is well-documented other forms of disease are characterized by areas of fibrosis or fatty infiltration in the myocardium often due to genetic mutations affecting intercellular desmosomes Comprehensive genetic testing including whole exome sequencing could clarify the contribution of various arrhythmogenic heart diseases to unexplained sports-related SCASCD
Improving this knowledge will benefit ongoing discussions about enhancing the content and effectiveness of pre-participation screening for athletes Moreover identifying the cause of SCASCD is critical for the victims and their families Understanding the cause may help families come to terms with the event and assist in preventing recurrence for successfully resuscitated individuals Furthermore since most hereditary heart diseases follow an autosomal dominant inheritance pattern each first-degree relative has a 50 chance of carrying the same genetic mutation Predictive testing clinical assessment and if necessary preventive treatment can be offered to these family members to reduce the risk of arrhythmic events
Statistical Analysis
Data analyses will be performed using specialized software with a significance threshold set at 5 Hypotheses will be formulated bilaterally
A descriptive analysis of the collected population data will be conducted Qualitative variables will be presented as numbers and percentages while quantitative variables will be described using the mean standard deviation median interquartile range minimum and maximum values
For the primary analysis of the main outcome the cause of sports-related SCASCD will be described in terms of numbers and percentages along with the corresponding 95 confidence intervals
For the secondary analyses the judgment criteria both overall and by vital status survived or deceased will be described in numbers and percentages with 95 confidence intervals
The beneficial effects of moderate physical activity on health are well-established However it is also well-proven that intense sports participation increases the risk of cardiovascular events by 24 to 45 times before the age of 35 in individuals with known or unknown heart conditions Sudden cardiac arrest SCA sometimes leading to sudden cardiac death SCD is the most dramatic event linked to sports
Before the age of 35 sports-related SCASCD is rare occurring in 07 to 27 per 100000 athletes which amounts to approximately 80 cases per year according to two French prospective studies Despite its rarity these events are often traumatic and highly publicized presenting a significant public health and safety concern Non-traumatic sports-related SCASCD is primarily of cardiovascular origin irrespective of the level of sports participation In most cases SCA results from ventricular arrhythmia caused by known or undiagnosed arrhythmogenic cardiovascular disease which varies by the victims age After the age of 35 atheromatous coronary artery disease accounts for 80-85 of cases However before the age of 35 a wider range of etiologies are observed Arrhythmogenic genetic heart diseases-structural eg arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy or non-structural eg channelopathies-are the most frequent causes Congenital abnormalities particularly anomalous connection of coronary artery represent the second most common cause Acquired heart diseases such as fibrous scars mainly post-myocarditis and atheromatous coronary lesions are less frequently involved In this younger population classical autopsy often fails to determine the cause in more than 40 of cases leading to the term sudden arrhythmic syndrome
Few prospective studies have combined classical autopsy with systematic genetic analysis to identify the cause of SCASCD in the general young population with no specific link to sports One Australian study demonstrated the value of genetic testing identifying a clinically relevant cardiac genetic variant for sudden death in 27 of cases Moreover the same pathology was identified in 13 of relatives of the victims who underwent clinical and genetic screening Another small Swedish study n15 focusing specifically on channelopathies in cases of negative autopsies revealed the disease in 40 of victims families through genetic analysis
Additionally the role of acute or chronic toxic substance intake has been suggested albeit without formal proof as a factor promoting sports-related SCASCD Toxicological screening is thus recommended as part of the etiological assessment Including toxicological analysis alongside other etiological evaluations could help clarify the impact of illicit substances on sports-related SCASCD
Justifications for the Study
No prospective study has systematically combined the recommended hospital assessment in cases of successful resuscitation or the recommended medical autopsy in the event of death with global genetic and toxicological analyses in victims of sports-related SCASCD
This combined approach is justified for several reasons First it would enhance our understanding of the etiologies of these events Notably so-called idiopathic left ventricular hypertrophy is found in more than 10 of sports-related SCD cases following classical autopsies Further genetic exploration could help determine whether these anatomical forms are pathological Additionally many arrhythmic cardiac diseases are associated with an elevated risk of sports-related SCASCD While arrhythmogenic right ventricular cardiomyopathy is well-documented other forms of disease are characterized by areas of fibrosis or fatty infiltration in the myocardium often due to genetic mutations affecting intercellular desmosomes Comprehensive genetic testing including whole exome sequencing could clarify the contribution of various arrhythmogenic heart diseases to unexplained sports-related SCASCD
Improving this knowledge will benefit ongoing discussions about enhancing the content and effectiveness of pre-participation screening for athletes Moreover identifying the cause of SCASCD is critical for the victims and their families Understanding the cause may help families come to terms with the event and assist in preventing recurrence for successfully resuscitated individuals Furthermore since most hereditary heart diseases follow an autosomal dominant inheritance pattern each first-degree relative has a 50 chance of carrying the same genetic mutation Predictive testing clinical assessment and if necessary preventive treatment can be offered to these family members to reduce the risk of arrhythmic events
Statistical Analysis
Data analyses will be performed using specialized software with a significance threshold set at 5 Hypotheses will be formulated bilaterally
A descriptive analysis of the collected population data will be conducted Qualitative variables will be presented as numbers and percentages while quantitative variables will be described using the mean standard deviation median interquartile range minimum and maximum values
For the primary analysis of the main outcome the cause of sports-related SCASCD will be described in terms of numbers and percentages along with the corresponding 95 confidence intervals
For the secondary analyses the judgment criteria both overall and by vital status survived or deceased will be described in numbers and percentages with 95 confidence intervals
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None