Alan Sugrue1, Martin van Zyl1, Nick Enger1, Katie Mancl1, Benjamin W Eidem2, Jae K Oh3, J Martijn Bos4, Samuel J Asirvatham5, Michael J Ackerman6. 1. Department of Cardiovascular Medicine, Division of Heart Rhythm Services, Mayo Clinic, Rochester, Minnesota, USA. 2. Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology, Mayo Clinic, Rochester, Minnesota, USA; Department of Cardiovascular Medicine, Division of Cardiovascular Ultrasound Mayo Clinic, Rochester, Minnesota, USA. 3. Department of Cardiovascular Medicine, Division of Cardiovascular Ultrasound Mayo Clinic, Rochester, Minnesota, USA. 4. Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology, Mayo Clinic, Rochester, Minnesota, USA; Department of Molecular Pharmacology & Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, Minnesota, USA. 5. Department of Cardiovascular Medicine, Division of Heart Rhythm Services, Mayo Clinic, Rochester, Minnesota, USA; Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology, Mayo Clinic, Rochester, Minnesota, USA. 6. Department of Cardiovascular Medicine, Division of Heart Rhythm Services, Mayo Clinic, Rochester, Minnesota, USA; Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology, Mayo Clinic, Rochester, Minnesota, USA; Department of Molecular Pharmacology & Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, Minnesota, USA. Electronic address: ackerman.michael@mayo.edu.
Abstract
BACKGROUND: The ability to identify those patients at the highest phenotypic risk for long QT syndrome (LQTS)-associated life-threatening cardiac events remains suboptimal. OBJECTIVES: This study sought to validate the association between electromechanical window (EMW) negativity, as derived from echocardiography, and symptomatic versus asymptomatic status in patients with LQTS. METHODS: We analyzed a cohort of 651 patients with LQTS (age 26 ± 17 years; 60% females; 158 symptomatic; 51% LQTS type 1; 33% LQTS type 2; 11% LQTS type 3; 5% multiple mutations) and 50 healthy controls. EMW was calculated as the difference between the interval from QRS onset to aortic valve closure midline, as derived for continuous-wave Doppler, and the electrocardiogram-derived QT interval for the same beat. RESULTS: A negative EMW was found among nearly all patients with LQTS compared to controls, with more profound EMW negativity in patients with symptomatic LQTS compared to those with asymptomatic LQTS (-52 ± 38 ms vs. -18 ± 29 ms; p < 0.0001). Logistic regression identified EMW, heart rate-corrected QT interval (QTc), female sex, and LQTS genotype as univariate predictors of symptomatic status. After multivariate analysis, EMW remained an independent predictor of symptomatic status (odds ratio for each 10-ms decrease in EMW: 1.37; 95% confidence interval: 1.27 to 1.48; p < 0.0001). EMW outperformed QTc in predicting symptomatic patients (area under the curve: 0.78 vs. 0.70; p = 0.01). After training and implementation, EMW correlation from echocardiographic sonographers showed excellent reliability (intraclass correlation coefficient: 0.93; 95% confidence interval: 0.89 to 0.96). CONCLUSIONS: In this validation study, patients with a history of LQTS-associated life-threatening cardiac events had a more profoundly negative EMW. EMW outperformed heart rate-corrected QT interval as a predictor of symptomatic status. EMW is now a clinically validated risk factor. In December 2019, our institution's echocardiography clinical practice committee approved use of EMW for patients with LQTS, making it a routinely reported echocardiographic finding.
BACKGROUND: The ability to identify those patients at the highest phenotypic risk for long QT syndrome (LQTS)-associated life-threatening cardiac events remains suboptimal. OBJECTIVES: This study sought to validate the association between electromechanical window (EMW) negativity, as derived from echocardiography, and symptomatic versus asymptomatic status in patients with LQTS. METHODS: We analyzed a cohort of 651 patients with LQTS (age 26 ± 17 years; 60% females; 158 symptomatic; 51% LQTS type 1; 33% LQTS type 2; 11% LQTS type 3; 5% multiple mutations) and 50 healthy controls. EMW was calculated as the difference between the interval from QRS onset to aortic valve closure midline, as derived for continuous-wave Doppler, and the electrocardiogram-derived QT interval for the same beat. RESULTS: A negative EMW was found among nearly all patients with LQTS compared to controls, with more profound EMW negativity in patients with symptomatic LQTS compared to those with asymptomatic LQTS (-52 ± 38 ms vs. -18 ± 29 ms; p < 0.0001). Logistic regression identified EMW, heart rate-corrected QT interval (QTc), female sex, and LQTS genotype as univariate predictors of symptomatic status. After multivariate analysis, EMW remained an independent predictor of symptomatic status (odds ratio for each 10-ms decrease in EMW: 1.37; 95% confidence interval: 1.27 to 1.48; p < 0.0001). EMW outperformed QTc in predicting symptomatic patients (area under the curve: 0.78 vs. 0.70; p = 0.01). After training and implementation, EMW correlation from echocardiographic sonographers showed excellent reliability (intraclass correlation coefficient: 0.93; 95% confidence interval: 0.89 to 0.96). CONCLUSIONS: In this validation study, patients with a history of LQTS-associated life-threatening cardiac events had a more profoundly negative EMW. EMW outperformed heart rate-corrected QT interval as a predictor of symptomatic status. EMW is now a clinically validated risk factor. In December 2019, our institution's echocardiography clinical practice committee approved use of EMW for patients with LQTS, making it a routinely reported echocardiographic finding.
Authors: Kristin Wisløff-Aase; Helge Skulstad; Kristina Haugaa; Per Snorre Lingaas; Jan Otto Beitnes; Per Steinar Halvorsen; Andreas Espinoza Journal: Physiol Rep Date: 2022-04
Authors: Katja E Odening; Henk J van der Linde; Michael J Ackerman; Paul G A Volders; Rachel M A Ter Bekke Journal: Eur Heart J Date: 2022-08-21 Impact factor: 35.855