BackgroundAn elegant bedside provocation test has been shown to aid the diagnosis of long‐QT syndrome (LQTS) in a retrospective cohort by evaluation of QT intervals and T‐wave morphology changes... Show moreBackgroundAn elegant bedside provocation test has been shown to aid the diagnosis of long‐QT syndrome (LQTS) in a retrospective cohort by evaluation of QT intervals and T‐wave morphology changes resulting from the brief tachycardia provoked by standing. We aimed to prospectively determine the potential diagnostic value of the standing test for LQTS.Methods and ResultsIn adults suspected for LQTS who had a standing test, the QT interval was assessed manually and automated. In addition, T‐wave morphology changes were determined. A total of 167 controls and 131 genetically confirmed patients with LQTS were included. A prolonged heart rate–corrected QT interval (QTc) (men ≥430 ms, women ≥450 ms) at baseline before standing yielded a sensitivity of 61% (95% CI, 47–74) in men and 54% (95% CI, 42–66) in women, with a specificity of 90% (95% CI, 80–96) and 89% (95% CI, 81–95), respectively. In both men and women, QTc≥460 ms after standing increased sensitivity (89% [95% CI, 83–94]) but decreased specificity (49% [95% CI, 41–57]). Sensitivity further increased (P<0.01) when a prolonged baseline QTc was accompanied by a QTc≥460 ms after standing in both men (93% [95% CI, 84–98]) and women (90% [95% CI, 81–96]). However, the area under the curve did not improve. T‐wave abnormalities after standing did not further increase the sensitivity or the area under the curve significantly.ConclusionsDespite earlier retrospective studies, a baseline ECG and the standing test in a prospective evaluation displayed a different diagnostic profile for congenital LQTS but no unequivocal synergism or advantage. This suggests that there is markedly reduced penetrance and incomplete expression in genetically confirmed LQTS with retention of repolarization reserve in response to the brief tachycardia provoked by standing. Show less
Als gevolg van de grote technologische vooruitgang in de gezondheidszorg worden in toenemende mate gegevens verzameld tijdens de uitvoering van klinische onderzoeken. Het is evenwel essentieel om... Show moreAls gevolg van de grote technologische vooruitgang in de gezondheidszorg worden in toenemende mate gegevens verzameld tijdens de uitvoering van klinische onderzoeken. Het is evenwel essentieel om te beseffen dat gegevens op zich van weinig of geen waarde zijn. Ten behoeve van hun optimale bruikbaarheid dienen gegevens geanalyseerd, geïnterpreteerd en verwerkt te worden. Machine learning-strategieën kunnen hiertoe nuttige en adequate oplossingen bieden. Dit proefschrift bevat machine learning-benaderingen toegepast op verschillende klinische datasets. De klassieke gegevens bestaan uit elektrische signalen van het electrocardiogram (ecg) verkregen bijgezonde proefpersonen, de innovatieve gegevens zijn afkomstig vanmetingen in een rijsimulator, en de opkomende gegevens zijn afgeleid van dna-analyse van de micro-organismen die op de huid voorkomenvan patiënten met huidziekten. We toonden aan dat het aantal ECG’s van invloed was op de nauwkeurigheid van geschatte verlenging van het qt-interval voor alle ingezette qt-correctieformules. Met behulp van SHapley AdditiveexPlanations (shap)-waarden werd de impact van de individuele kenmerken op de voorspelling van fysiologische leeftijd van het hart bepaald. We maakten gebruik van machine learning voor een betere beoordeling van de rijprestaties van bestuurders die medicijnen gebruikten. Tot slot lieten we zien dat de belangrijkste micro-organismen voor discriminatie van seborrroische dermatitis – naast Cutibacterium en Staphylococcus – kwamen relatief weinig voor, waardoor men deze micro-organismen in standaardanalyses eenvoudig over het hoofd kan zien. Daarmee hebben we aangetoond dat machine learning kanworden toegepast op gegevens die zijn afgeleid van klinische onderzoeken om in een vroeg stadium het effect van medicijnen en andere interventies op te sporen en te evalueren. Show less
Wall, H.E.C. van der; Hassing, G.J.; Doll, R.J.; Westen, G.J.P. van; Cohen, A.F.; Selder, J.L.; ... ; Gal, P. 2022
ObjectiveThe aim of the present study was to develop a neural network to characterize the effect of aging on the ECG in healthy volunteers. Moreover, the impact of the various ECG features on aging... Show moreObjectiveThe aim of the present study was to develop a neural network to characterize the effect of aging on the ECG in healthy volunteers. Moreover, the impact of the various ECG features on aging was evaluated.Methods & resultsA total of 6228 healthy subjects without structural heart disease were included in this study. A neural network regression model was created to predict age of the subjects based on their ECG; 577 parameters derived from a 12‑lead ECG of each subject were used to develop and validate the neural network; A tenfold cross-validation was performed, using 118 subjects for validation each fold. Using SHapley Additive exPlanations values the impact of the individual features on the prediction of age was determined. Of 6228 subjects tested, 1808 (29%) were females and mean age was 34 years, range 18-75 years. Physiologic age was estimated as a continuous variable with an average error of 6.9 ± 5.6 years (R2 = 0.72 ± 0.04). The correlation was slightly stronger for men (R2 = 0.74) than for women (R2 = 0.66). The most important features on the prediction of physiologic age were T wave morphology indices in leads V4 and V5, and P wave amplitude in leads AVR and II.ConclusionThe application of machine learning to the ECG using a neural network regression model, allows accurate estimation of physiologic cardiac age. This technique could be used to pick up subtle age-related cardiac changes, but also estimate the reversing of these age-associated effects by administered treatments. Show less
Wall, H.E.C. van der; Hassing, G.J.; Doll, R.J.; Westen, G.J.P. van; Cohen, A.F.; Selder, J.L.; ... ; Gal, P. 2022
ObjectiveThe aim of the present study was to develop a neural network to characterize the effect of aging on the ECG in healthy volunteers. Moreover, the impact of the various ECG features on aging... Show moreObjectiveThe aim of the present study was to develop a neural network to characterize the effect of aging on the ECG in healthy volunteers. Moreover, the impact of the various ECG features on aging was evaluated.Methods & resultsA total of 6228 healthy subjects without structural heart disease were included in this study. A neural network regression model was created to predict age of the subjects based on their ECG; 577 parameters derived from a 12‑lead ECG of each subject were used to develop and validate the neural network; A tenfold cross-validation was performed, using 118 subjects for validation each fold. Using SHapley Additive exPlanations values the impact of the individual features on the prediction of age was determined. Of 6228 subjects tested, 1808 (29%) were females and mean age was 34 years, range 18–75 years. Physiologic age was estimated as a continuous variable with an average error of 6.9 ± 5.6 years (R2 = 0.72 ± 0.04) . The correlation was slightly stronger for men (R2 = 0.74) than for women (R2 = 0.66). The most important features on the prediction of physiologic age were T wave morphology indices in leads V4 and V5, and P wave amplitude in leads AVR and II.ConclusionThe application of machine learning to the ECG using a neural network regression model, allows accurate estimation of physiologic cardiac age. This technique could be used to pick up subtle age-related cardiac changes, but also estimate the reversing of these age-associated effects by administered treatments. Show less
BACKGROUND Adult long QT syndrome (LQTS) patients have inadequate corrected QT interval (QTc) shortening and an abnormal T-wave response to the sudden heart rate acceleration provoked by standing.... Show moreBACKGROUND Adult long QT syndrome (LQTS) patients have inadequate corrected QT interval (QTc) shortening and an abnormal T-wave response to the sudden heart rate acceleration provoked by standing. In adults, this knowledge can be used to aid an LQTS diagnosis and, possibly, for risk stratification. However, data on the diagnostic value of the standing test in children are currently limited. OBJECTIVE To determine the potential value of the standing test to aid LQTS diagnostics in children. METHODS In a prospective cohort including children (<= 18 years) who had a standing test, comprehensive analyses were performed including manual and automated QT interval assessments and determination of T-wave morphology changes. RESULTS We included 47 LQTS children and 86 control children. At baseline, the QTc that identified LQTS children with a 90% sensitivity was 435 ms, which yielded a 65% specificity. A QTc >= 490 ms after standing only slightly increased sensitivity (91%, 95% confidence interval [CI]: 80%-98%) and slightly decreased specificity (58%, 95% CI: 47%-70%). Sensitivity increased slightly more when T-wave abnormalities were present (94%, 95% CI: 82%-99%; specificity 53%, 95% CI: 42%-65%). When a baseline QTc >= 440 ms was accompanied by a QTc >= 490 ms and T-wave abnormalities after standing, sensitivity further increased (96%, 95% CI: 85%-99%) at the expense of a further specificity decrease (41%, 95% CI: 30%-52%). Beat-to-beat analysis showed that 30 seconds after standing, LQTS children had a greater increase in heart rate compared to controls, which was more evidently present in LQTS boys and LQTS type 1 children. CONCLUSION In children, the standing test has limited additive diagnostic value for LQTS over a baseline electrocardiogram, while T-wave abnormalities after standing also have limited additional value. The standing test for LQTS should only be used with caution in children. Show less
Fienieg, B.; Hassing, G.J.; Wall, H.E.C. van der; Westen, G.J.P. van; Kemme, M.J.B.; Adiyaman, A.; ... ; Gal, P. 2020
Background Previous studies reported that hypo- and hyperthermia are associated with several atrial and ventricular electrocardiographical parameters, including corrected QT (QTc) interval.... Show moreBackground Previous studies reported that hypo- and hyperthermia are associated with several atrial and ventricular electrocardiographical parameters, including corrected QT (QTc) interval. Enhanced characterization of variations in QTc interval and normothermic body temperature aids in better understanding the underlying mechanism behind drug induced QTc interval effects. The analysis' objective was to investigate associations between body temperature and electrocardiographical parameters in normothermic healthy volunteers.Methods Data from 3023 volunteers collected at our center were retrospectively analyzed. Subjects were considered healthy after review of collected data by a physician, including a normal tympanic body temperature (35.5-37.5 degrees C) and in sinus rhythm. A linear multivariate model with body temperature as a continuous was performed. Another multivariate analysis was performed with only the QT subintervals as independent variables and body temperature as dependent variable.Results Mean age was 33.8 +/- 17.5 years and mean body temperature was 36.6 +/- 0.4 degrees C. Body temperature was independently associated with age (standardized coefficient [SC] = -0.255, P < .001), female gender (SC = +0.209, P < .001), heart rate (SC = +0.231, P < .001), P-wave axis (SC = -0.051, P < .001), J-point elevation in lead V4 (SC = -0.121, P < .001), and QTcF duration (SC = -0.061, P = .002). In contrast, other atrial and atrioventricular (AV) nodal parameters were not independently associated with body temperature. QT subinterval analysis revealed that only QRS duration (SC = -0.121, P < .001) was independently associated with body temperature.Conclusion Body temperature in normothermic healthy volunteers was associated with heart rate, P-wave axis, J-point amplitude in lead V4, and ventricular conductivity, the latter primarily through prolongation of the QRS duration. Show less
Fienieg, B.; Hassing, G.J.; Wall, H.E.C. van der; Westen, G.J.P. van; Kemme, M.J.B.; Adiyaman, A.; ... ; Gal, P. 2020
BACKGROUNDPrevious studies reported that hypo- and hyperthermia are associated with several atrial and ventricular electrocardiographical parameters, including corrected QT (QTc) interval. Enhanced... Show moreBACKGROUNDPrevious studies reported that hypo- and hyperthermia are associated with several atrial and ventricular electrocardiographical parameters, including corrected QT (QTc) interval. Enhanced characterization of variations in QTc interval and normothermic body temperature aids in better understanding the underlying mechanism behind drug induced QTc interval effects. The analysis' objective was to investigate associations between body temperature and electrocardiographical parameters in normothermic healthy volunteers.METHODSData from 3023 volunteers collected at our center were retrospectively analyzed. Subjects were considered healthy after review of collected data by a physician, including a normal tympanic body temperature (35.5-37.5°C) and in sinus rhythm. A linear multivariate model with body temperature as a continuous was performed. Another multivariate analysis was performed with only the QT subintervals as independent variables and body temperature as dependent variable.RESULTSMean age was 33.8 ± 17.5 years and mean body temperature was 36.6 ± 0.4°C. Body temperature was independently associated with age (standardized coefficient [SC] = -0.255, P < .001), female gender (SC = +0.209, P < .001), heart rate (SC = +0.231, P < .001), P-wave axis (SC = -0.051, P < .001), J-point elevation in lead V4 (SC = -0.121, P < .001), and QTcF duration (SC = -0.061, P = .002). In contrast, other atrial and atrioventricular (AV) nodal parameters were not independently associated with body temperature. QT subinterval analysis revealed that only QRS duration (SC = -0.121, P < .001) was independently associated with body temperature.CONCLUSIONBody temperature in normothermic healthy volunteers was associated with heart rate, P-wave axis, J-point amplitude in lead V4, and ventricular conductivity, the latter primarily through prolongation of the QRS duration. Show less
Background Early prehospital recognition of critical conditions such as ST-segment-elevation myocardial infarction (STEMI) has prognostic relevance. Current international electrocardiographic STEMI... Show moreBackground Early prehospital recognition of critical conditions such as ST-segment-elevation myocardial infarction (STEMI) has prognostic relevance. Current international electrocardiographic STEMI thresholds are predominantly based on individuals of Western European descent. However, because of ethnic electrocardiographic variability both in health and disease, there is a need to reevaluate diagnostic ST-segment elevation thresholds for different populations. We hypothesized that fulfillment of ST-segment elevation thresholds of STEMI criteria (STE-ECGs) in apparently healthy individuals is ethnicity dependent.Methods and Results HELIUS (Healthy Life in an Urban Setting) is a multiethnic cohort study including 10 783 apparently healthy subjects of 6 different ethnicities (African Surinamese, Dutch, Ghanaian, Moroccan, South Asian Surinamese, and Turkish). Prevalence of STE-ECGs across ethnicities, sexes, and age groups was assessed with respect to the 2 international STEMI thresholds: sex and age specific versus sex specific. Mean prevalence of STE-ECGs was 2.8% to 3.4% (age/sex-specific and sex-specific thresholds, respectively), although with large ethnicity-dependent variability. Prevalences in Western European Dutch were 2.3% to 3.0%, but excessively higher in young (<40 years) Ghanaian males (21.7%-27.5%) and lowest in older (40 years) Turkish females (0.0%). Ethnicity (sub-Saharan African origin) and other variables (eg, younger age, male sex, high QRS voltages, or anterolateral early repolarization pattern) were positively associated with STE-ECG occurrence, resulting in subgroups with >45% STE-ECGs.Conclusions The accuracy of diagnostic tests partly relies on background prevalence in healthy individuals. In apparently healthy subjects, there is a highly variable ethnicity-dependent prevalence of ECGs with ST-segment elevations exceeding STEMI thresholds. This has potential consequences for STEMI evaluations in individuals who are not of Western European descent, putatively resulting in adverse outcomes with both over- and underdiagnosis of STEMI. Show less
Lende, M. van der; Arends, J.B.; Lamberts, R.J.; Tan, H.L.; Lange, F.J. de; Sander, J.W.; ... ; Thijs, R.D. 2019
Elevated blood pressure induces electrocardiographic changes and is associated with an increase in cardiovascular disease later in life compared to normal blood pressure levels. The purpose of this... Show moreElevated blood pressure induces electrocardiographic changes and is associated with an increase in cardiovascular disease later in life compared to normal blood pressure levels. The purpose of this study was to evaluate the association between normal to high normal blood pressure values (90–139/50–89 mmHg) and electrocardiographic parameters related to cardiac changes in hypertension in healthy young adults.Data from 1449 volunteers aged 18–30 years collected at our centre were analyzed. Only subjects considered healthy by a physician after review of collected data with systolic blood pressure values between 90 and 139 mmHg and diastolic blood pressure values between 50 and 89 mmHg were included. Subjects were divided into groups with 10 mmHg systolic blood pressure increment between groups for analysis of electrocardiographic differences. Backward multivariate regression analysis with systolic and diastolic blood pressure as a continuous variable was performed.The mean age was 22.7 ± 3.0 years, 73.7% were male. P-wave area, ventricular activation time, QRS-duration, Sokolow–Lyon voltages, Cornell Product, J-point–T-peak duration corrected for heart rate and maximum T-wave duration were significantly different between systolic blood pressure groups. In the multivariate model with gender, body mass index and cholesterol, ventricular rate (standardized coefficient (SC): +0.182, p < .001), ventricular activation time in lead V6 (SC= +0.065, p = .048), Sokolow–Lyon voltage (SC= +0.135, p < .001), and Cornell product (SC= +0.137, p < .001) were independently associated with systolic blood pressure, while ventricular rate (SC= +0.179, p < .001), P-wave area in lead V1 (SC= +0.079, p = .020), and Cornell product (SC= +0.091, p = .006) were independently associated with diastolic blood pressure.Blood pressure-related electrocardiographic changes were observed incrementally in a healthy young population with blood pressure in the normal range. These changes were an increased ventricular rate, increased atrial surface area, ventricular activation time and increased ventricular hypertrophy indices on a standard 12 lead electrocardiogram. Show less
Hassing, G.J.; Wall, H.E.C. van der; Westen, G.J.P. van; Kemme, M.J.B.; Adiyaman, A.; Elvan, A.; ... ; Gal, P. 2019
IntroductionAn increased body mass index (BMI) (>25 kg/m2) is associated with a wide range of electrocardiographic changes. However, the association between electrocardiographic changes and BMI in... Show moreIntroductionAn increased body mass index (BMI) (>25 kg/m2) is associated with a wide range of electrocardiographic changes. However, the association between electrocardiographic changes and BMI in healthy young individuals with a normal BMI (18.5–25 kg/m2) is unknown. The aim of this study was to evaluate the association between BMI and electrocardiographic parameters.MethodsData from 1,290 volunteers aged 18 to 30 years collected at our centre were analysed. Only subjects considered healthy by a physician after review of collected data with a normal BMI and in sinus rhythm were included in the analysis. Subjects with a normal BMI (18.5–25 kg/m2) were divided into BMI quartiles analysis and a backward multivariate regression analysis with a normal BMI as a continuous variable was performed.ResultsMean age was 22.7 ± 3.0 years, mean BMI was 22.0, and 73.4% were male. There were significant differences between the BMI quartiles in terms of maximum P-wave duration, P-wave balance, total P-wave area in lead V1, PR-interval duration, and heart axis. In the multivariate model maximum P-wave duration (standardised coefficient (SC) = +0.112, P < 0.001), P-wave balance in lead V1 (SC = +0.072, P < 0.001), heart axis (SC = −0.164, P < 0.001), and Sokolow-Lyon voltage (SC = −0.097, P < 0.001) were independently associated with BMI.ConclusionIncreased BMI was related with discrete electrocardiographic alterations including an increased P-wave duration, increased P-wave balance, a leftward shift of the heart axis, and decreased Sokolow-Lyon voltage on a standard twelve lead electrocardiogram in healthy young individuals with a normal BMI. Show less
Akintola, A.A.; Pol, V. van de; Bimmel, D.; Maan, A.C.; Heemst, D. van 2016
