Dr Antonis Pantazis, consultant cardiologist from the Heart Hospital in London, discusses how new criteria aims to identify the risks in those without definite disease and ensure they receive proper follow-up care
The structural abnormalities of arrhythmogenic right ventricular cardiomyopathy (ARVC) were first described in 1736 but only in the last few decades has the condition gained clinical recognition.
In late 1980’s ARVC was reported to be a major cause of sudden death in the young and in competitive athletes. Changes of the heart muscle at a cellular level were also described. Later, a number of genes were identified as responsible for the condition.
Genes come in pairs in the DNA. In the pairs of genes encoding the proteins related to ARVC, one copy is usually normal and the other has a change. The degree of symptoms depends on a number of genetic and possibly environmental factors.
Therefore, mild variants of the condition often exist. The diagnosis in those cases can be difficult because the features are mild and non-specific (the symptoms may be present in other conditions too).
This is often the situation in relatives of people who were first diagnosed with ARVC. This means that most people at risk of developing the condition are only mildly affected but poses difficulties in the process of diagnosis. And in the relatively small group of patients with ARVC who are at risk of life-threatening arrhythmias, early diagnosis would hopefully help to prevent this risk.
Over the years, and as it became evident that the clinical appearance of this familial condition was very variable, cardiologists realised that no single test was able to diagnose it.
With careful clinical observations and research, understanding of this condition significantly increased and in 1994 the first description of diagnostic criteria was published by a group of experts led by Professor William McKenna, professor of cardiology and now at the Heart Hospital in London.
The criteria consisted of a list of parameters describing structural, cellular and electrical features of the heart and findings in families.
The criteria were divided into “major” and “minor” depending on whether the features were considered to be strongly or exclusively associated with ARVC or not. Some changes frequently observed in ARVC (such as on an ECG) were left out of the criteria when they were also commonly observed in many other conditions.
Later it became obvious that this family condition does not fully show itself in all relatives who carry the change (mutation) in the ARVC gene but often remains subtle.
To address this problem and to identify those who have a mild form of the clinical condition, a study published by Professor McKenna’s group in 2002 suggested that the presence of the condition in a family should be taken into account and that the review of diagnostic test results should be more sensitive to the possibility of ARVC in the relatives.
So the 1994 criteria helped to identify a significant number of patients with ARVC, and the systematic screening of their relatives with the more sensitive 2002 modified criteria unveiled the broader range of the condition.
Nevertheless, in the years following these publications, and taking advantage of the clinical experience from the family screening and genetic testing, it was increasingly recognised that a number of people with features of the condition would still not meet the diagnostic criteria despite having a mild clinical ARVC.
Concerns have also been raised about the risk of those who did not meet the criteria. Although it did not appear that the risk was high in the majority of them, cardiologists would have felt more confident if these people were followed and assessed.
Last but not least, the diagnostic tools and processes have improved over the years and the need for a robust method of evaluation emerged. So in 2010, and after a detailed and long discussion among experts, new ARVC diagnostic criteria have been published. The terms “definite” and “borderline” ARVC have been introduced to reflect the various aspects of the clinical presentation of the condition and to enable the clinician to inform those individuals with minor abnormalities, but not definite disease, that they are at risk and require regular follow up.
The new criteria aims to improve the sensitivity of the diagnostic tests, to gain benefit from the advances in the technology of the diagnostic tools and processes, and hopefully maintain the ability to discriminate between different diseases. One of the main ideas of the new criteria is to measure cardiac features and give numbers instead of using subjective interpretation.
Based on the results of research studies, even those limited by the relatively small numbers of participating individuals, the new criteria attempted to draw distinct lines between the normal and abnormal readings of various tests, especially in the imaging tests.
This may still not perfectly discriminate those who are mildly affected from the unaffected but the rationale is surely important for the accurate diagnosis by cardiologists who might not have the experience of ARVC cases and will provide a common language among them.
Especially in the emerging field of cardiac MRI, myths that were generated previously and became popular due to lack of experience have been eliminated and a systematic approach is being recommended.
The inclusion of mild structural changes was removed from the new criteria as these changes were found to be extremely non-specific and subjective.
Changes in the way the heart’s cellular findings are read have been implemented by the new criteria. These are in keeping with the new, more objective way the numbers and features of the cardiac test results are being interpreted.
The new criteria also attempts to reduce uncertainty about the condition and prevent early cases being missed. Patients with subtle expression who may occasionally have a risk of arrhythmia can be better identified and monitored.
Their risk will be more efficiently reduced if the subtle diagnostic features are put in the right context and recognised as a disease expression than if the features are dismissed.
Fortunately, no major action needs to be taken in most of cases but appropriate clinical screening and re-evaluation can be planned based on the diagnostic information.
In the research field, it is also very important that the right individuals are recruited in the studies and that the broader expression of the condition is recognised with more sensitive criteria.
Despite the improvements in the new criteria, it cannot be ignored that any criteria or clinical guidelines are only aiming to offer help to the clinicians and standardise the provided care.
In situations where there is ambiguity, experience and expertise are required. Especially in hereditary and therefore genetic conditions where a new era has emerged in both the understanding and the clinical practice, it is not infrequent that the variability, complexity and overlap with other conditions are not entirely captured by recommendations, guidelines or criteria.
In those cases, clinical experience is apparently the safest way to resolve uncertainties.