Can a TV Quiz Show Kill You?
How a Quiz Show Death Led to a Brilliant Medical Career
Reproduced from Substack by Subscription
Many cardiologists, and especially electrophysiologists, know the name, Peter J. Schwartz, from Milan, Italy. Professor (Prof.) Schwartz is known for his work on Long QT Syndrome (LQTS) and sudden cardiac death (SCD), but he has also made significant contributions to related areas of cardiovascular medicine. I first knew of his work from his studies using a canine model to examine the role of exercise training in reducing SCD.(1) That model placed a reversible snare around the left anterior descending artery in dogs. The snare could be tightened to produce ischemia during exercise, and often ventricular fibrillation (VF). Prof. Schwartz and colleagues showed that the possibility of VF was markedly reduced by exercise training and that the VF risk returned after the dogs were detrained. They attributed this increased resistance to VF to enhanced vagal tone.
These studies are important to those of us interested in the risks and benefits of exercise, but Prof. Schwartz’s greatest contributions are his studies of LQTS. Prof. Schwartz has recounted his 50 years in this field. (2). I have reviewed it before for PracticeUpdate (3), but am expanding my review here.
Prof. Schwartz’ paper starts with the lines, “This is not a review article on the long QT syndrome (LQTS). It is the account of a privilege. “ The privilege is to take care of the patients with LQTS. What a great reminder that it remains a privilege to practice medicine and to try to help patients.
Prof. Schwartz states that “It all started on 14 October 1970, during the most popular TV quiz program in Italy, shown in prime time and watched by millions”. During that show, a 19-year old, female contestant with a history of fainting during exertional and emotional stress responded to a question by collapsing and dying. She had previously been admitted to another hospital in Milan where her ECG was considered normal, but Prof. Schwartz reviewed the ECG later and found that the QT was markedly prolonged.
The autopsy of the quiz contestant was unrevealing, but the victim’s 9-year-old sister had similar symptoms so the mother had the sister admitted to the University of Milan Hospital. Prof. Schwartz was starting his clinical career, and was responsible for four clinical beds in the department of internal medicine. Fortunately, the daughter was admitted to one of his beds. Her ECG showed marked QT prolongation, but none of the senior physicians were impressed because at that time textbooks considered the QT interval as essentially useless information. As Prof. Schwartz writes, “That was my epiphany for the realization that textbooks can, and often should, be challenged.” The girl was scheduled for an exercise test, but became nervous when she saw the testing equipment and developed T-wave alternans, a harbinger of ventricular fibrillation. The test was cancelled.
Prof. Schwarz was able to implicate the prolonged QT as the cause through library research. This was well before PubMed and other computer search engines. Medical researchers used Index Medicus to search for relevant articles. Prof. Schwartz found the cases of prolonged QT reported by Jervell and Lange-Nielsen in deaf children and by Romano and Ward in patients with normal hearing. Almost all of the life-threatening cardiac events in these cases occurred during activities with increased sympathetic activity. Prof. Schwartz also wanted to know if T-wave alternans was related to LQTS. So, he reviewed every issue of Index Medicus from 1920 to 1970 to look for other cases with T-wave alternans. He found only seven cases of T-wave alternans that were not associated with LQTS
Prof. Schwartz, during his initial years of clinical work, was also performing basic research on single-fiber recordings from cardiac sympathetic nerves. He used this laboratory to demonstrate that in animal models, left stellate ganglion stimulation increased cardiac sympathetic tone, prolonged the QT and produce T-wave alternans.
He started his patient on beta-blockers because he recognized that his patient’s and many of the reported events in the literature occurred during physical and emotional stress. She later experienced a stress-related event demonstrating that beta-blockade alone was insufficient so she underwent left stellate ganglion ablation in 1973. She did well, and Prof. Schwartz was the best man at her wedding. She died in an accident in 2018.
Prof. Schwartz became interested in what had happened to the other LQTS patients reported in the literature. As he says, “Shyness was never my weakness and I started asking anyone who had published even a single case of LQTS what happened to the patient after the publication … luckily, I kept all my LQTS correspondence.” He wrote to Prof. Anton Jervell, of Jervell and Lange-Nielsen Syndrome fame. Jervell was in his 70’s at the time. Several of these letters are included in the publication. Prof. Schwarz ultimately collected 203 patients. In 1977, he met Arthur Moss, MD, from the University of Rochester, who had performed the first left stellate ganglion ablation in 1971. Dr. Moss was interested in the cases that Prof. Schwartz had accumulated and suggested that they form the International Registry for LQTS. This registry has been instrumental in developing strong pedigrees for genetic studies.
One of the more interesting genetic studies came out of Prof. Schwartz’ collaboration with colleagues in South Africa. They used a South African family to examine why family members with identical LQTS genetic defect had markedly different clinical outcomes. They uncovered several “modifier genes”. Most of these modifies worsened the phenotype but one reduced the severity of the syndrome by altering the ubiquitin pathway. The ubiquitin pathway catabolizes normal and abnormal proteins, including ion channels. The asymptomatic, genotype positive family members had a gene that inhibits ion channel catabolism so that the normal ion channels persisted longer on the cell membrane. This prevented the abnormal depolarization that would have occurred if the normal ion channels had been catabolized more rapidly.
An amazing coincidence in the South African story is that one of the founders of this family with LQTS was a man who had immigrated to South Africa from the Netherlands in 1690 to work for the Company of the Indies. That man’s name was Pieter Swart, the Dutch equivalent of Peter Schwartz.
Maybe destiny is more than genes.
So, what are the rules:
- You can have a lot of success by picking an area that fascinates you and pursuing it.
- Listen to, but don’t always believe, the experts. If Prof. Schwartz had accepted that the QT was not important, his career would have never happened.
- Don’t be shy. Prof. Schwartz’ international registry started because he was willing to ask others, who were older and more famous, to share their cases.
The genetics of LQTS has been reviewed.(5)
1. S S Hull Jr 1, E Vanoli, P B Adamson, R L Verrier, R D Foreman, P J Schwartz. Exercise training confers anticipatory protection from sudden death during acute myocardial ischemia. Circulation. . 1994 Feb;89(2):548-52. PMID: 8313542
2. Schwartz, PJ. 1970-2020: 50 years of research on the long QT syndrome-from almost zero knowledge to precision medicine. Eur Heart J. 2021 Mar 14;42(11):1063-1072. PMID: 33057695
4. Schwartz PJ, Crotti L, George AL. Modifier genes for sudden cardiac death. Eur Heart J 2018;39:3925–3931.
5. Schwartz PJ, Ackerman MJ, Antzelevitch C, Bezzina C, Borggrefe M, Cuneo B, Wilde AAM. Inherited cardiac arrhythmias. Nat Rev Dis Prim. 2020;6:58. PMID: 32678103
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