Comparative Medicine: A “One Health” Approach to Sudden Cardiac Death

Sudden cardiac death is a major public health issue. But humans are not the only ones affected. Dogs and cats are also susceptible to it and share many pathophysiological and genetic similarities with humans. Pets could therefore benefit from the knowledge gathered on this topic in human medicine, just as they could serve as valuable research models for discovering new therapeutic approaches that benefit global health—both human and animal.   Sudden death is one of the leading causes of death among humans in Western countries. A total of 400,000 people die from it each year in the United States. In approximately 85% of cases, the cause is cardiac in origin. Sudden cardiac death is a sudden, non-traumatic, fatal event in a patient with no other life-threatening medical conditions. Death generally occurs within one hour of the onset of symptoms. In France, approximately 60,000 people are affected each year—about one in every thousand—particularly men, who are three to four times more likely to be affected than women. This condition, as sudden as it is unexpected, represents a major public health challenge in our country. Significant efforts are underway to improve the management of cardiac arrest, as well as to advance prevention strategies based on epidemiological, genetic, and therapeutic research. This research and new findings published in human medicine could benefit dogs and cats, which also suffer from sudden death. Indeed, sudden cardiac death also occurs in pets, but pathophysiological and prevalence data are much scarcer. Could discoveries in human medicine be applied to animals, enhance our understanding of animal health, and potentially aid in their care? To find out, researchers reviewed the most significant structural, electrical, and ischemic heart diseases in humans, dogs, and cats that could lead to sudden death, focusing on prevalence and pathophysiological and genetic similarities.   The results show that many heart diseases responsible for sudden death in animals and humans share similar underlying arrhythmogenic mechanisms and closely related genetics (although knowledge of the underlying genetics in dogs and cats is still limited). In humans, a large body of scientific evidence points to coronary artery disease as the primary cause of sudden cardiac death. Cardiomyopathies, such as dilated cardiomyopathy, hypertrophic cardiomyopathy, or arrhythmogenic right ventricular cardiomyopathy, are implicated, as are “electrical” heart diseases without structural abnormalities. In dogs, the same electrical and structural heart conditions can cause sudden death. In particular, dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are the two most common structural causes of sudden cardiac death in dogs. In cats, hypertrophic cardiomyopathy appears to play a more significant role, and the disease shares many similarities with the human form.   While numerous mutations at multiple loci have been linked to sudden cardiac death in humans, only a few mutations associated with dilated cardiomyopathy and sudden death have been identified in dogs, for example in the PLN (phospholamban) and TTN (titin) genes. However, significant progress is being made. For now, the limited data available on the mutations underlying the structural and electrical disorders that cause sudden cardiac death in dogs and cats seem to confirm a genetic origin, as in humans.   Sudden cardiac death therefore shares many commonalities among humans, dogs, and cats. Researchers conclude that findings published in human medicine could inform future veterinary studies, but the reverse is also true. Unlike laboratory animals such as mice and rats, dogs and cats could serve as good spontaneous models for many structural and primary cardiac and electrical disorders underlying sudden cardiac death in humans. Pets could be used to study the development of drugs targeting new therapeutic pathways or treatment modalities, such as gene therapy or stem cell therapy, for the benefit of global health. But before reaching that stage, more research is needed to better understand the pathogenesis, pathophysiology, genetics, and prevention of sudden cardiac death in animals, in order to more accurately identify similarities between different species.