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Abstract

Background: Understanding the incidence and causes of young sudden cardiac death (YSCD) is crucial to guide preventative strategies.

Aims: The aims of this thesis are to: 1. report on the incidence of cardiac and sudden cardiac death (SCD) in individuals under the age of 35 years in England and Wales, and identify any temporal trends in mortality over two decades. 2. Investigate the role and implications of the expert cardiac autopsy in the setting of SCD, specifically in the context of gender, age, circumstances of death and distinguishing between similar disease entities. 3. Following a novel pandemic, from a cardiac screening perspective, investigate the prevalence and diagnostic significance of denovo electrocardiogram (ECG) changes post COVID-19 infection in elite soccer players.

Methods: Large scale population level data from the Office for National Statistics (ONS) and the Cardiac Risk in the Young Centre for Cardiac Pathology (CRY-CCP) was analysed. This correlated to mortality in individuals aged 0-34 years, between 2001 to 2021. Descriptive statistics and Poisson log-linear models were created to assess trend shifts over time. All autopsy evaluations and histological analyses were conducted by expert cardiac pathologists in accordance with established protocols. Furthermore, a multicentre observational study was performed between March 2020 and May 2022 where 511 consecutive soccer players, from the English, Dutch and Brazilian Football Associations with COVID-19 infection were evaluated.

Results: The incidence of cardiac and YSCD in England and Wales is 1.68 per 100,000 individuals per annum. The most prevalent conditions were ischaemic heart disease (28.4%), cardiomyopathies (25.9%) and sudden arrhythmic death syndrome (SADS) (21.8%). An overall downward trend in cardiac mortality over 21-years was observed, whilst the incidence of SADS demonstrated an 8.5% increment annually (p<0.001) up until 2010. Deaths attributed to cardiomyopathies and SADS peak during the 10-to-19 and 20-to-29-year age group.

Data from the CRY-CCP revealed: similar increments in SADS deaths over the study period. SCD occurs less frequently in female athletes and SADS is more frequent than male counterparts. Macro and microscopic evaluation of hearts demonstrated that mitral valve abnormalities were over four-fold more common in individuals with hypertrophic cardiomyopathy (HCM) and may be used as supportive criteria to differentiate from idiopathic left ventricular hypertrophy (ILVH). In young individuals with HCM, SCD was the first manifestation of the condition in 79% of cases and a high age-related variability in terms of the circumstances of death was observed. Individuals aged 10 to 15 years appear to be the most vulnerable in terms of exercise related SCD. Data from the CRY-CCP revealed that myocarditis is a rare cause of SCD in non-hospitalised individuals, however almost 20% reported prodromal cardiac symptoms prior to death.

Following evaluation of 511 soccer players with COVID-19 infection, 3% of athletes demonstrated de-novo ECG changes and 88% were diagnosed with cardiac inflammation. Athletes revealing de-novo ECG changes had a higher prevalence of cardiac symptoms (71% vs 12%, p<0.0001) and longer median symptom duration (5 days, IQR 3-10) compared with athletes without de-novo ECG changes (2 days, IQR 1-3, p<0.001). Most athletes exhibited cardiac symptoms, however, de-novo ECG changes contributed to a diagnosis of cardiac inflammation in 20% of athletes without cardiac symptoms. Following a median follow up of 270 days (IQR: 133-487 days), there were no adverse cardiac events among infected athletes in the entire cohort. All athletes identified with cardiac inflammation returned to play following conventional risk stratification tests and tailored exercise prescriptions without adverse events over a median follow up period of 479 days (IQR: 268-520 days).

Conclusions: Overall, my thesis provides novel insights into a decreasing trend in cardiac and SCD amongst young individuals in England and Wales. The incidence of SCD is likely underestimated and conceited efforts are required to ameliorate ambiguity in mortality coding with the aim of facilitating appropriate evaluation of surviving family members. The emphasis on expert cardiac histopathology assessment following SCD is crucial in elucidating the cause, distinguishing between similar disease entities, and providing insights for preventative strategies. Despite COVID-19 infection being a highly contagious disease, in the context of elite sport, most athletes experience a mild and self-limiting illness, with no adverse cardiac sequalae on follow-up. Novel insights from a cardiac screening and ECG perspective demonstrate a role for comparison of serial ECGs in the context of viral illness to facilitate tailored downstream investigations.

Publication Type:	Thesis (Doctoral)
Subjects:	Q Science > Q Science (General) R Medicine > R Medicine (General)
Departments:	School of Health & Medical Sciences > Cardiovascular and Genomics Research Institute School of Health & Medical Sciences > School of Health & Medical Sciences Doctoral Theses Doctoral Theses

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