Conundrum of Sudden Cardiac Death. Part 1
Conundrum of Sudden Cardiac Death. Part 1
SCD in Athletes: Introduction
To read the full Disclaimer: Click here | Last Updated: 1/24/23
Conundrum of Sudden Cardiac Death Part 1
SCD in Athletes: Introduction
One of the most terrifying medical phenomena known to humanity is the unexpected sudden death which affects apparently healthy individual and is not caused by the violent body shattering physical force, apparent poisoning or drowning. This horrific way of dying is a nightmarish threat which accompanied mankind throughout history (Ref). The claims have been made that the first recorded sudden death took place in the ancient Egypt during the era of the Sixth Dynasty between 2625-2475 B.C. (Ref), (Ref), (Ref). The Ebers papyrus written around 1500 BC contains the description of the sudden death which can be attributed to Ventricular Fibrillation (Ref). Hippocrates who lived in the 4th century BC has given a general description of sudden cardiac death in his Aphorisms II, 41 (Ref). However, the scientific understanding of the sudden cardiac death took place in 19th century when British physiologist John A MacWilliam first proposed the rational electrophysiological hypothesis as the most likely explanation of sudden death (Ref).
The sudden death can occur due to combination of cardiac, respiratory, neurological and other unknown factors - as it happens in cases of Sudden Unexpected Death in Epilepsy (SUDEP). However, typically term “sudden death” it is understood as the reference to “sudden cardiac death (SCD)”, “out-of-hospital sudden unexpected death” (OHSUD). Those names describe the sudden cessation of cardiac activity with hemodynamic collapse, typically due to sustained ventricular tachycardia/ventricular fibrillation (Ref).
Significance and Paradox of SCD
Based upon the quoted above historical records sudden cardiac death is not a novel phenomenon. It had terrified the general public and puzzled physician and scientists for centuries. The understanding and preventing sudden cardiac death is considered to be “one of the most challenging tasks in Cardiology” - by leading cardiology experts (Ref). In addition to being terrifying and resistant to preventive measures, this calamity is not as rare as the conventional wisdom would like us to believe. It is estimated that it may account for 15-20% of deaths in western countries, and it is a cause of the majority of deaths due to cardiovascular factors (Ref).
However, there is an intriguing paradox related to the SCD. On one hand the substantial significance of the SCD appears to be appreciated by medical experts, general public and politicians.
There are well known in the scientific community Sudden Cardiac Death research programs such as The Oregon Sudden Unexpected Death Study (Ref), (Ref), POST SCD study (Ref), (Ref), SUDDEN study (Ref), (Ref) and ROC Resuscitation Outcomes Consortium (Ref), The Minneapolis Heart Institute Foundation SCD in Athletes Registry (Ref). The academic excellence centers dedicated exclusively to SDC such as Center for Cardiac Arrest Prevention (CCAP) also have been created (Ref).
The public appeared to be engaged in those efforts. The benevolent associations with participation of public - dedicated to promotion of research dealing with SCD such as Sudden Cardiac Arrest Association (Ref) and Sudden Cardiac Death Awareness Research Foundation (Ref) have been established.
Legislators contributed to the cause of preventing SCD as well. Among other similar legislative acts Pennsylvania state legislators passed Sudden Cardiac Arrest Prevention Act, in August of 2012 (Ref). In April 2015, Tennessee Legislature has passed the Sudden Cardiac Arrest Prevention Act (Ref). In March of 2017, the Ohio Senate passed Bill 252, known as Lindsay’s Law (Ref). California Governor has signed the Eric Paredes Sudden Cardiac Arrest Prevention Act into law on September 29, 2016.
In the view of all the above one could assume that SCD research have been funded most generously. Surprisingly this is not a case. Paradoxically, the opposite is true. There is a long line of evidence demonstrating that counterintuitively the National Institutes of Health (NIH) keep investing significantly less money in SCD/SCA research in comparison to the other causes of death (Ref), (Ref), (Ref) , (Ref), (Ref), (Ref), (Ref). For instance in 2017 Coute et al reported that for every year of healthy life lost because of disease, the NIH invests:
$284 for diabetes,
$89 for stroke,
$53 for ischemic heart disease and
The follow-up paper by the same author published in 2021 confirmed that funding allocated by NIH for studying SCD are surprisingly scarce (Ref). In the interview given to the University of Michigan Newspaper (Ref) R.W. Neumar who was the senior author of the 2017 paper on NIH funding of SCD (Ref) stated that this scarcity of SCD funding was unexpected, hard to justify and puzzling. He explained that underfunding of SCD research by NIH is especially unfortunate - since unlike other major causes of death - SCD is not receiving much funding from pharmaceutical industry. He suggested that this situation could be perhaps caused by the lack of interests of researchers in applying for such NIH funds. However, this scenario seems rather uncanny given the described above efforts of the scientific community.
CW Callaway has offered much more detailed analysis of the potential reason for this paradox in his 2017 commentary published in (Ref). In brief, Callaway identified following major reasons for under-funding of the SCD by both the NIH and the industry:
Public misunderstanding of SCD. The general lay public and politicians are certainly disturbed by the episodes of SCD which affected their family members and about those they have learned from the press. However, according to Callaway, laypeople lack the deep understanding of the SCD phenomenon. In public discussions and in the popular press - SCD is frequently confused with the “massive heart attack”and viewed as the “fatalistic” event that cannot be neither prevented nor treated effectively. Sudden death affecting older individuals may be wrongly perceived by their family members as “natural death.” Most popular press reports dealing with SCD tend to concentrate on cases of athletes and celebrities, while omitting the fact that SCD can affect anyone. For this reason many people may assume that SCD is rather infrequent and perhaps limited to the “elites”. This may lead to the underestimation of the high prevalence and enormous societal burden of SCD. In such a settings, a large part of the public, while obviously distressed by the existence of SCD, is not getting motivated enough to exert the pressure on their politicians to do something about it.
Lack of surviving advocates. Indeed, unlike patients affected by chronic conditions, individuals affected by SCD simply do not survive to become advocates for more research on their disease. The families of those patients are certainly devastated but eventually most of them simply move on and show no interest in persistent advocacy efforts.
Difficulties with tracking cases of SCD. Due to numerous logistical problems and various definitions of SCD it is notoriously difficult to accurately record the precise number of cases of SCD. Moreover, it is very difficult if not impossible on occasions - to try to make the comparisons of frequency of SCD between various periods of times and even various territories. This is because definitions of SCD, pre- and post-mortem diagnostic capabilities as well as death reporting technologies have been changing dramatically with time and territory. Under such conditions it is still possible to see the overall big impact of SCD but the lack of precise data is discouraging for many laypeople who are unaware about those limitations.
The Research barriers: There are numerous barriers which are specific to SCD that make performance of successful SCD studies very difficult. Such obstacles include the logistical, conceptual, and design difficulties that can make the studies of SCD either extremely burdensome or even unattainable:
In Clinical SCD research:
Logistical difficulties include multiple organ involvement, multiple specialists involved with each patient, different locations of treatment (out‐of‐hospital, emergency department, intensive care unit, rehabilitation facilities), and distribution of patients at many different hospitals with varying capacities.
Conceptual difficulties include heterogeneity of the patient population, lack of validated outcome measures, lack of accepted surrogate outcomes, and huge variability in background clinical care.
Design difficulties include the need to account for the interaction of multiple interventions and for informative censoring (withdrawal of life support prior to reaching an outcome). In addition to these issues, cardiac arrest patients are acutely ill and usually unconscious, requiring studies to obtain consent from distraught families or exception from informed consent using complex approval processes.
In basic SCD research:
Logistical difficulties include need for prolonged intensive care in realistic animal models, desirability of large animal models over rodents for modeling organ interactions in humans, and difficulty of accounting for underlying diseases that cause cardiac arrest.
Conceptual difficulties include the facts that singular mechanisms are hard to evaluate when every organ system is affected by cardiac arrest, that anesthetics that are not used for humans must be used in animal studies, and that simple geometric differences between species influence important outcomes (eg, brain herniation, drug distribution, chest compression depth, ventilation–compression relationships).
Design difficulties include variability in results and specific techniques between different laboratories, absence of multilaboratory networks, and paucity of standardized laboratory models.
Given these complexities, a shortage of qualified or sufficiently motivated investigators may at least partly explain why there are not more applications and more grants at NIH for cardiac arrest research.
Outwardly Low Profitability of Prophylaxis of SCD. Theoretically all human beings seek measures to prolong their own life and lives of the loved ones. Therefore one would assume that Pharmaceutical industry would see a big profit in researching and developing drugs and modalities aimed at both prevention and treatment of SCD. However, the same described above mechanisms of misunderstanding by general public and same research barriers which cause underfunding by the NIH impact negatively on the pharmaceutical industry willingness to engage in the work in this area.
Interestingly, recent public interest in the cases of SCD that are purported to be potentially linked to the putative side effects of COVID-19 vaccines could provide the much needed impetus to reanimate the research of the dreaded syndrome of SCD. In the view of this situation we will perform here the review of the facts and opinions relating to the phenomenon of SCD in general and to its putative link to COVID-19 and COVID-19 vaccination.
To be continued…