50 years of research on the long QT syndrome — from almost zero knowledge to precision medicine
Wow, it’s a tough assignment to pick my choice for top story of 2021. There were so many interesting publications covered in PracticeUpdate Cardiology. Let me take you through my thought process to my selection.
I considered selecting the Self-Assessment Method for Statin Side-effects Or Nocebo (SAMSON) trial. SAMSON used an “n-of-1” design to examine statin-associated muscle symptoms (SAMS).1,2 The 60 participants who had developed SAMS after only 2 weeks of treatment served as their own controls and were randomly assigned to atorvastatin 20 mg daily, placebo, or a no-pill for 4 x 1-month trials over 12 months. The mean symptom score was not different during placebo (15.4) and statin treatment (18.7), but it was higher than during the no-pill period (8.0), demonstrating the “nocebo effect,” or that taking a pill, even a placebo, can produce symptoms in some patients. I eliminated SAMSON from selection because: getting SAMS after only 2 weeks of treatment suggests that this group was more twitchy than the usual SAMS patients; there was no attempt to determine that the SAMS were real before enrollment by using a pre-study run-in trial; and only 49 participants finished the study.
I considered selecting the substudy from the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which examined the effect of statins on cognition in adults aged ≥65 years.3,4 Participants had a median age of 74 at the start and, over a median of 4.7 years, showed no difference in cognitive decline on or off a statin. These results are reassuring about statin use in the elderly, but the hazard ratio for probable Alzheimer’s disease approached statistical significance, raising concern and begging for the results of the ongoing, randomized controlled clinical trials (RCCTs) examining the effects of statins on cognition. I did not select this entry because it was not an RCCT.
I also considered selecting the retrospective analysis of the effect of testosterone (T) on cardiovascular disease (CVD) in 204,857 US veterans.5 Neither cutaneous nor injected T increased CVD risk, and cutaneous T was associated with reduced risk. These results are important because T may make aging men feel better, but clinicians are reluctant to prescribe T because of concerns about increasing CVD risk. But, again, this was not an RCCT.
The Low-Dose Colchicine 2 trial randomized 5522 patients with chronic CVD6 to colchicine 0.5 mg daily or placebo, and it added to the studies showing reduced CVD events with colchicine. It’s amazing that with all our great treatments we can still find ways to reduce CVD events using an old drug. I did not select this article because prior studies have already shown benefit from colchicine.
So, in the end, I selected the European Heart Journal article on Professor Peter Schwartz’s 50-year career studying the long QT syndrome (LQTS).7,8 It is an amazing mystery of how a chance encounter with a patient led Professor Schwartz to pursue his life’s work and to make so many contributions to our knowledge of LQTS. Dr. Schwartz wrote, “It all started on 14 October, 1970, during the most popular TV quiz programme 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. Dr. Schwarz subsequently cared for the victim’s 9-year-old sister. Her ECG was markedly abnormal, and his curiosity led to his career in LQTS. His personal story is both educational and entertaining. This article is my top pick for 2021 because if you have not read it, you should!