Kulkarni, Veda

AbstractIntroductionLong QT syndrome (LQTS) is a cardiac channelopathy characterized by QT prolongation and a potential for arrhythmic syncope, sudden cardiac arrest or deaths (SCA/SCD). It has been speculated that patients with LQTS might have a primary sinoatrial node (SAN) phenotype of chronotropic insufficiency (CI). This has not been demonstrated convincingly before because of the potentially confounding effects of beta blocker (BB) therapy. Herein, we set out to determine whether untreated patients with LQTS demonstrate intrinsic CI.Methods and ResultsA retrospective review of all treadmill exercise stress tests (TEST) was performed on patients with one of the three most common LQTS genotypes: LQT1, LQT2, and LQT3. For each patient, the first TEST completed while off BB was analyzed. Patients with prior left cardiac sympathetic denervation (LCSD) therapy were excluded. CI was defined as having an age‐ and gender‐predicted peak heart rate (HR) < 85% and/or a predicted HR reserve (HRR) < 80%. Overall, 463 LQTS patients (245 LQT1, 125 LQT2, and 93 LQT3) were included (267 female [58%]; mean age at time of TEST [29 ± 17 years]). Mean % predicted peak HR for all LQTS patients was 87.6% (range 42.9% ‐ 119.1%) and mean % predicted HRR was 80% (range 19.1% ‐ 153%). Overall, half of all LQTS patients (n = 234; 51%) displayed CI; 64% of patients with LQT1 (n = 157), 37% with LQT2 (n = 46), and 33% with LQT3 (n = 31). Patients with LQT1 were most likely to exhibit CI compared to patients with LQT2 (p < .0001) and LQT3 (p < .0001). CI was significantly more common in LQT1 compared to controls (p < .0001), while there was no difference between LQT2 (p = .5) or LQT3 and controls (p > .9). Presence of CI was not a predictor of LQTS‐associated symptoms, BB side effects or likelihood of future breakthrough cardiac events (BCE).ConclusionsPatients with LQTS, particularly LQT1, demonstrate a SAN phenotype of CI. If assessing BB therapy effect by impact on peak HR, the patient's pretreatment peak HR, rather than an age‐ and gender‐predicted maximum HR, should be used.

AbstractBackgroundLong QT syndrome (LQTS) is a sudden death predisposing condition characterized by ECG‐derived prolongation of the QT interval. Previous studies have demonstrated that the supine‐stand test may aid in the diagnosis of LQTS as patients fail to shorten their QT interval in response to standing up. The aim of this study was to evaluate the diagnostic accuracy of ECG data derived from standard protocol, clinically performed treadmill exercise stress tests (TESTs) in their ability to mimic the formal supine‐stand test.MethodsWe performed a retrospective review of 478 TESTs from patients evaluated for LQTS. Patients referred for evaluation of LQTS but who were dismissed as normal served as controls. Heart rate & QT values were obtained from standard protocol TESTs.ResultsOverall, 243 patients with LQTS (125 LQT1, 63 LQT2, 55 LQT3; 146 [60%] female, mean age at TEST 30 ± 17 years) and 235 controls (142 [60%] female, mean age 24 ± 15 years) were included. The paired ΔQTc (QTcStand‐QTcSupine) was similar between LQTS (−5 ± 26) and controls (−2 ± 25; p = .2). During position change, the QT interval shortened by ≥20 ms in 33% of LQTS patients, remained unchanged in 62%, and increased in 5% of LQTS patients which was similar to controls (shortened in 40%, unchanged in 54%, and increased in 6% of controls; p = .2). Receiver‐operator curve analysis to test the diagnostic ability of supine‐stand ΔQT performed poorly in differentiating LQTS from controls with an of AUC 0.52 (p = .4).ConclusionTESTs should be used with caution when trying to interpret supine‐stand changes for diagnosis of LQTS.

Introduction: Sudden cardiac arrest (SCA) and death (SCD) are the most serious sequelae of many genetic heart diseases (GHDs). Increased awareness of this has led to increased detection in employment screenings. For patients in high-risk jobs, premature and potentially unnecessary termination from their profession, rather than “Return-to-Work (RTW),” has become an undesired consequence of this awareness. The objective of this study is to evaluate the outcomes of patients with GHDs in high-risk professions who were allowed to RTW. Methods: We performed a retrospective review of 3,641 working-age patients referred for evaluation of a potential GHD between 6/2000-12/2021 to identify those either in or being recruited into a high-risk profession. A profession was defined as “high-risk” if it is safety-sensitive or required regular medical evaluations. Charts were reviewed for medical history, RTW decision making, and breakthrough cardiac events (BCEs). Results: Overall, 33 patients [(0.9%); 3 females (9%); mean age at diagnosis 25 ± 15 years] had been either put on hold from their high-risk job (n = 15; 45%) or disqualified as a recruit (18; 55%) prior to our evaluation due to their GHD diagnosis. This included 15 military, 10 pilots, 6 law enforcement and first responders, and 2 commercial driver license professionals and recruits. Most patients were diagnosed with Long QT syndrome (n = 23; 70%). After treatment initiation, 14 (93%) professionals and 16 (89%) recruits received physician RTW approval while 3 (9%) patients did not receive RTW approval due to disease severity and/or unwillingness to initiate treatment. Of the remaining 14 professionals that received physician RTW approval, 4 (29%) were not allowed to return to their jobs, while 14/16 recruits (88%) were not permitted to start their career. None of the RTW-approved patients had a BCE after evaluation (160.7 follow-up years). Conclusions: Patients with GHDs in high-risk professions are often terminated due to perceived SCA/SCD risk. However, within our small cohort, the risk of BCEs in optimally treated patients was low. This data suggests that the certification process of individuals in these high-risk and safety-sensitive occupations should be further examined and potentially modified.