ESC William Harvey Lecture in Basic Science: Prof. Cristina Basso
Sudden cardiac death and autopsy in the era of molecular medicine
01 Sep 2024
The presenter of this year’s ESC William Harvey Lecture in Basic Science, Professor Cristina Basso (University of Padua - Padova, Italy), has considerably expanded knowledge across cardiac pathologies with her anatomo-clinical correlations in cardiovascular science and their translational application in the clinical field.
What are the key themes of your lecture?
In today’s era of molecular medicine, it is tempting to think that the solution to every problem lies at the level of the gene. In contrast to this, the theme of my lecture honours the work of William Harvey who discovered the blood circulation by observation and calculation, recognising the key role of morphological features at autopsy. Even in 2024, the first manifestation of underlying heart disease in young people can be sudden cardiac death (SCD) and specialised autopsy is the only opportunity to try to understand the cause.
Arrhythmogenic cardiomyopathy (ACM), an inherited condition characterised by fibro-fatty replacement of myocardial tissue and a known cause of SCD, is a good example of a disease identified by autopsy in young victims. Frequently affecting the left ventricle, ACM is particularly difficult to diagnose in the clinical setting and tissue characterisation is commonly required for confirmation.
Autopsy investigation also led to the identification of mitral valve prolapse, another condition linked to SCD in some patients. This disease was previously thought to always be benign and reversible by surgical replacement or repair of the valve. However, a link with SCD was made following examination of cardiac tissue from a series of young cases, which revealed mitral valve leaflet redundancy with localised fibrosis of the myocardium.1,2 Autopsy-driven findings have prompted research to identify which patients with these conditions are at risk of SCD and to devise strategies to treat, and preferably prevent, arrhythmic manifestations.
More recently, prospective investigation of all SCD victims in the North-East of Italy was able to demonstrate no increased SCD rates in young people both during the COVID-19 pandemic and after the introduction of vaccination. Causes of SCD in young people were consistent with pre-pandemic causes as established by rigorous autopsy and no increase in the prevalence of myocarditis has been observed.3
What are the most important knowledge gaps?
I have been studying SCD for almost 34 years and still one of the biggest gaps in knowledge is understanding why so many cases of SCD, particularly among individuals in early childhood or adolescence, present with what appears to be a gross and histologically normal heart. Deaths from structural CVD have in general decreased in line with our improved knowledge about causes, diagnostic features, prevention and effective treatment. It is somewhat sobering, therefore, to note the relative increase in the proportion of deaths from non-structural heart disease that escape early identification by cardiac imaging. Ion channel abnormalities are one explanation for the electrical instability; however, where individuals have undergone tests prior to SCD, there are often no abnormalities in electrocardiograms. There is a huge need for more research to investigate other potential causes of instability, for example, Purkinje fibre network abnormalities and intrinsic arrhythmias.
What are the most promising avenues of research?
The current interest of my research group is to try to get a more complete understanding of the aetiology and pathogenesis of non-ischaemic myocardial scarring. Not all scars are arrhythmogenic and linked to potential SCD, not all scars are genetically determined.4 Instead, they may be due to other factors and, therefore, do not carry the risk of an inherited disease with familial recurrence. Distinguishing between the different types is important for determining future steps. Novel preclinical models should help to elucidate underlying mechanisms and we have achieved good results using mouse5 and zebrafish6 models in ACM. Above all, we need to comprehensively collect data, including family screening, genetic screening, acquired risk factors and drug-related issues, to allow us to identify patients at risk and so prevent the early deaths of often young people.
References
- Basso C, et al. Circulation. 2019;140:952–964.
- Basso C, et al. Circulation. 2015;132:556–566.
- De Gaspari M, et al. Circulation. 2023;148:2069–2071.
- Corrado D, et al. Eur Heart J Suppl. 2023;25(Suppl C):C144–C154.
- Cason M, et al. Heart Rhythm. 2021;18:1394–1403.
- Celeghin R, et al. Cell Death Discov. 2023;9:441.
