Ariaratnam Gobikrishna MD
The best way to leave this world is without pain or suffering. Most of us hope for a long, healthy life, followed by a peaceful end. Yet life does not always follow that script. In a strange and almost cruel way, it is often the young who leave suddenly, without suffering, while those who live longer are more likely to face illness and decline. While the young may be spared physical suffering, it is their loved ones who bear the deepest pain—the shock of an untimely loss and the lingering fear that the same fate may be waiting for them.
After the initial period of grief, families—especially parents—often turn their attention to their surviving children. That is when the role of the physician shifts. The time for consolation gradually gives way to careful exploration. In earlier times, such deaths might have been attributed to horoscopes, omens, spiritual predictions, or the “evil eye.” Today, we rely on science—but even then, our answers are limited. If medical records are spotty and no autopsy has been performed, finding a cause can feel like wild goose chase. Even with autopsies, around 40 percent of cases remain unexplained.
For many young people, sudden deaths are linked to a few known inherited problems involving the heart or the brain. These organs are crucial for sustaining life, and if either fails abruptly, death can occur within moments. These inherited genetic changes may affect the structure or electrical function of the heart, or the blood vessels supplying the brain. Medically, the final event is often described as “cardiac arrest,” which usually means the heart suddenly goes into a chaotic rhythm and can no longer pump blood effectively. Less commonly, the heart may continue to beat without effectively pumping blood, eventually slowing and stopping altogether. In some cases, the brain is the first organ to fail, such as during a sudden bleed from an aneurysm (ballooning of arteries), even while the heart continues to pump for a prolonged period if oxygenation is maintained on a ventilator.
When there is no clear diagnosis and no autopsy, evaluation usually begins with the heart in first-degree relatives, as most known genetic causes of sudden death in the young originate there. From this starting point, testing is expanded as needed, guided by the circumstances of the death and the family history. Even if a definitive explanation is not found, this approach can uncover hidden risks and, in some cases, help prevent another tragedy.
A simple electrocardiogram, or EKG, is often the first step. This test records the heart’s electrical activity and can reveal patterns that suggest hidden conditions predisposing the heart to dangerous rhythms. Some patterns are so characteristic that they are considered “signature” findings, pointing toward specific conditions. Other changes may be nonspecific but unusual for a young person, prompting further investigation.
Some EKG patterns suggest the heart’s structure is affected. For example, an unusually tall and exaggerated tracing may indicate hypertrophic cardiomyopathy, a condition in which the heart muscle becomes abnormally thick. This is a common cause of sudden death in young athletes, often on the playing field. Another condition, Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), may show a subtle EKG finding called an epsilon wave. In this disorder, parts of the heart muscle are replaced by fatty or fibrous tissue, and dangerous rhythms are often triggered during intense physical activity.
Other conditions with classic EKG patterns affect the heart’s electrical system even when its structure appears normal. Brugada syndrome, more common in people of Asian descent, presents with a signature EKG pattern and can degenerate into chaotic rhythms and sudden death, often at rest but may be triggered by fever or illness. Long QT syndromes delay the heart’s electrical recovery, and sudden death may be triggered by swimming, sudden shocks, or loud noises, depending on the subtypes. In contrast, short QT syndrome shortens the recovery period, predisposing to arrhythmias even at rest. Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is triggered by surges of adrenaline during exercise or emotional stress; in rare cases, particularly during a treadmill test, its signature bidirectional rhythm can be seen on the EKG, but at rest the EKG may appear completely normal. Wolff-Parkinson-White (WPW) syndrome, which can run in families, may also degenerate into chaotic rhythms without warning, though the resting EKG usually shows its signature pattern. A common finding on routine EKGs, known as early repolarization, has recently been linked to sudden death in some families and is now recognized as early repolarization syndrome.
Sometimes, the EKG may not show a signature pattern, but it can reveal abnormalities that simply should not be present in a young person. These atypical findings often lead to further tests, such as an echocardiogram. Through this, doctors may find conditions like dilated cardiomyopathy, where the heart becomes enlarged and weak due to genetic causes, or left ventricular noncompaction, where the heart muscle does not form normally. When nonspecific abnormalities on ECGs in young women prompted further evaluation with echocardiography, a subset of a commonly considered benign condition—mitral valve prolapse—became evident. In some individuals, this abnormal laxity, often involving both leaflets but particularly the posterior leaflet, is associated with malignant arrhythmias and can lead to sudden death. This entity is now referred to as arrhythmogenic mitral valve prolapse. At times, even a simple cold-like illness can lead to severe inflammation of the heart muscle (myocarditis), resulting in abnormal EKG activity and chaotic rhythms that may lead to sudden death.
A rare condition called an anomalous coronary artery can occasionally lead to sudden death. It is often difficult to detect, and the diagnosis is usually made only during a detailed autopsy after an unexpected death. In living individuals, it may be suspected if someone faints during physical activity. In this condition, the arteries that supply blood to the heart have an unusual origin and course, which can become kinked or compressed during rapid heartbeats, particularly during exercise. Routine tests, such as echocardiograms, may miss the abnormal anatomy. Coronary CT scans provide the most reliable way to visualize these unusual coronary paths. Although congenital, this condition typically does not run in families.
If you’re really unfortunate, even a hard blow to the chest during a friendly sport can cause instantaneous death from deadly arrhythmias—a condition known as commotio cordis.
The sudden death of John Ritter, an American sitcom star, highlighted another important cause—the aorta, the body’s main artery. The aorta can develop a tear, called a dissection, or rupture completely. These problems can occur as part of broader genetic syndromes or on their own. A more common non-syndromic form is associated with a bicuspid aortic valve, in which the aortic valve has two flaps instead of three. This is often accompanied by a weakened aortic wall and may lead to valve dysfunction or aortic tear or even rupture. Familial aortopathy, as the name implies, can affect multiple family members and is caused by an inherited weakness in the aortic wall; it also increases the risk of sudden rupture.
Syndromic aortic conditions are often easier to recognize because they involve features beyond the aorta. Marfan syndrome is one example, with tall stature, long limbs, flexible joints, and characteristic facial features. Loeys–Dietz syndrome may include a split or bifid uvula. Ehlers–Danlos syndrome, especially the vascular type, is associated with fragile blood vessels. In all of these conditions, the underlying problem is a genetic weakness in the tissues that form the walls of arteries, making them vulnerable to sudden tearing or rupture.
Blood tests provide another important window into this complex situation. Despite the rarer conditions, the most common cause of sudden death in people over 30 remains coronary artery disease. Measuring cholesterol levels is crucial for survivors of sudden cardiac events and their first-degree relatives. Inherited high cholesterol, including familial and polygenic hypercholesterolemia, as well as elevated lipoprotein(a), can quietly accelerate plaque buildup from a young age. Combined with modern lifestyle factors, these conditions increase the risk of premature coronary disease and, in some cases, sudden cardiac death.
Turning to the brain, one of the main non-cardiac causes of sudden death in young people is bleeding from cerebral aneurysms. Most aneurysms occur sporadically, but some run in families, particularly when associated with conditions such as Ehlers–Danlos syndrome or polycystic kidney disease. Aneurysms can also occur in individuals born with coarctation of the aorta—a congenital narrowing of the vessel—although this is a congenital rather than familial condition. Patients with a diagnosis of seizures are also known to die unexpectedly.
Finally, another important cause of sudden death involves the collapse of the right side of the heart due to blood clots in the main arteries of the lungs, known as pulmonary embolism. This can result from prolonged inactivity, leg injuries, certain cancers, or use of oral contraceptives. In rare cases, a genetic tendency to form clots can allow blood clots to travel from the legs to the lungs, blocking the arteries and overwhelming the right heart. While familial cases are uncommon, pulmonary embolism remains a recognized cause of sudden death at all ages.
Beyond cardiac and vascular causes, one of the most common contributors to sudden death in modern times is illicit drug use. Without an autopsy, the exact cause often remains uncertain, and conclusions are frequently based on circumstantial evidence.
Having gone through this litany of tongue twisters, the known causes of sudden death may seem disparate, but the coup de grâce for many looks remarkably the same. Most sudden deaths result from the heart’s rhythm suddenly degenerating into chaotic electrical activity, ultimately causing abrupt cessation of cardiac function—the so-called “cardiac arrest.” This mechanism is not only the terminal event in people born with abnormal EKG patterns, such as long QT, Brugada, or CPVT, but also occurs in structural heart disease, brain bleeds, and even in certain drug overdose scenarios. In many of these situations, but not all, rescue involves the use of a defibrillator.
And that brings us to the innovation of the external defibrillator and some tidbits about those involved in its making. The first successful external direct-current (DC) defibrillation in a human was performed in 1962 in Boston. The landmark JAMA article reporting this achievement lists Dr. Bernard Lown, the innovator of the technique, along with Dr. Raghavan Amarasingham from Ceylon (Sri Lanka) and Dr. Jose Neuman from Argentina. This achievement paved the way for automated external defibrillators (AEDs), which are now ubiquitous in public spaces, allowing life-saving interventions even before medical personnel arrive.
It would take another two decades though before Dr. Michel Mirowski asked a crucial question: what if a life-threatening arrhythmia occurs when no one is around with an external defibrillator? And that prompted him to envision, despite constant criticism and widespread skepticism, a device that could be implanted to detect and terminate lethal heart rhythms automatically. Working in Baltimore in the late 1960s, he and his collaborators developed and refined the concept of the Implantable Cardioverter-Defibrillator (ICD), performing the first successful human implant in 1980 at John’s Hopkins. This device continuously monitors the heart and delivers a shock when needed, providing a life-saving option for people at high risk, particularly those for whom medications are ineffective or insufficient.
It is indeed a remarkable journey, uncovering the causes and remedies for this heart-wrenching problem that cuts short the lives of so many young people. Although the list of recognized entities responsible for sudden death may seem exhaustive, in my view it is only a starting point. These abnormalities were literally in front of our eyes all along—on ECGs, echocardiograms, CTs, and MRIs—yet they were often dismissed as normal variants or minor permutations. Each time, it took someone willing to connect the dots to recognize these as distinct syndromes. For example, Short QT syndrome was only formally described in the early 2000s by the Brugada brothers—how striking it is to have three eminent cardiologists in a single family—the same family who identified Brugada syndrome in 1992–1993. This underscores how recent some of these discoveries are, and with the advent of AI, I anticipate that such findings will proliferate even more rapidly, offering hope for earlier detection and prevention.
