Country differences in nocturnal sleep variability: Observations from a large-scale, long-term sleep wearable study.

STUDY OBJECTIVES: Country or regional differences in sleep duration are well-known, but few large-scale studies have specifically evaluated sleep variability, either across the work week, or in terms of differences in weekday and weekend sleep. METHODS: Sleep measures, obtained over 50 million night's sleep from ∼220,000 wearable device users in 35 countries, were analysed. Each person contributed an average of ∼242 nights of data. Multiple regression was used to assess the impact country of residence had on sleep duration, timing, efficiency, weekday sleep variability, weekend sleep extension and social jetlag. RESULTS: Nocturnal sleep was shorter and had a later onset in Asia than other regions. Despite this, sleep efficiency was lower and weekday sleep variability was higher. Weekend sleep extension was longer in Europe and the USA than in Asia, and was only partially related to weekday sleep duration. There were also cross-country differences in social jetlag although the regional differences were less distinct than for weekend sleep extension. CONCLUSIONS: In addition to regional differences in sleep duration, cross-country differences in sleep variability and weekend sleep extension suggest that using the latter as an indicator of sleep debt may need to be reconsidered. In countries exhibiting both short sleep and high weekday sleep variability, a culturally different means of coping with inadequate sleep is likely. Country or region differences in culture, particularly those related to work, merit closer examination as factors influencing the variability in normative sleep patterns around the world.

Thicker polyethylene inserts (≥ 13 mm) increase the risk for early failure after primary cruciate-retaining total knee arthroplasty (TKA): a single-centre study of 7643 TKAs.

PURPOSE: This study investigates whether thicker (PE) inserts lead to a greater risk for revision after TKA. The differences between the TKA designs of three manufacturers (NexGen, PFC Sigma, Triathlon) are also compared. METHODS: A total of 7643 primary TKA surgeries were included. PE inserts were divided into two groups-"thick PE inserts" with a thickness of 13 mm (mm) or more and "standard PE inserts" with a thickness of less than 13 mm. Three cruciate-retaining (CR) TKA designs (NexGen, PFC Sigma, Triathlon) were included in the study. The differences in failure rates between groups were investigated using Kaplan-Meier survival curves and Cox regression model with hazard ratios (HR). Failure rates were investigated short-term (< 2 years) and long-term (the whole follow-up period). The TKA designs were analysed both together and separately. RESULTS: During the whole follow-up period, there were 184 (2.4%) aseptic revisions. The thick PE insert group showed an increased risk for revision compared to the standard PE insert group in both short-term (< 2 years; HR 2.0, CI 1.3 to 3.2) and long term (> 2 years; HR 1.6, CI 1.1 to 2.3) follow-up. The highest revision rate was observed in patients who received the Triathlon TKA with a thicker PE insert (HR 2.6, CI 1.2 to 5.7). CONCLUSION: The results indicate that thicker PE inserts are associated with increased risk for revision in primary TKA. Further research is required to ascertain whether more conformed PE inserts or constrained knee designs instead of thick CR inserts will ultimately lead to better clinical outcomes. LEVEL OF EVIDENCE: III.

Prediction model for an early revision for dislocation after primary total hip arthroplasty.

Dislocation is one of the most common complications after primary total hip arthroplasty (THA). Several patient-related risk factors for dislocation have been reported in the previous literature, but only few prediction models for dislocation have been made. Our aim was to build a prediction model for an early (within the first 2 years) revision for dislocation after primary THA using two different statistical methods. The study data constituted of 37 pre- or perioperative variables and postoperative follow-up data of 16 454 primary THAs performed at our institution in 2008-2021. Model I was a traditional logistic regression model and Model II was based on the elastic net method that utilizes machine learning. The models' overall performance was measured using the pseudo R2 values. The discrimination of the models was measured using C-index in Model I and Area Under the Curve (AUC) in Model II. Calibration curves were made for both models. At 2 years postoperatively, 95 hips (0.6% prevalence) had been revised for dislocation. The pseudo R2 values were 0.04 in Model I and 0.02 in Model II indicating low predictive capability in both models. The C-index in Model I was 0.67 and the AUC in Model II was 0.73 indicating modest discrimination. The prediction of an early revision for dislocation after primary THA is difficult even in a large cohort of patients with detailed data available because of the reasonably low prevalence and multifactorial nature of dislocation. Therefore, the risk of dislocation should be kept in mind in every primary THA, whether the patient has predisposing factors for dislocation or not. Further, when conducting a prediction model, sophisticated methods that utilize machine learning may not necessarily offer significant advantage over traditional statistical methods in clinical setup.

Longitudinal profiling of metabolic ageing trends in two population cohorts of young adults.

BACKGROUND: Quantification of metabolic changes over the human life course is essential to understanding ageing processes. Yet longitudinal metabolomics data are rare and long gaps between visits can introduce biases that mask true trends. We introduce new ways to process quantitative time-series population data and elucidate metabolic ageing trends in two large cohorts. METHODS: Eligible participants included 1672 individuals from the Cardiovascular Risk in Young Finns Study and 3117 from the Northern Finland Birth Cohort 1966. Up to three time points (ages 24-49 years) were analysed by nuclear magnetic resonance metabolomics and clinical biochemistry (236 measures). Temporal trends were quantified as median change per decade. Sample quality was verified by consistency of shared biomarkers between metabolomics and clinical assays. Batch effects between visits were mitigated by a new algorithm introduced in this report. The results below satisfy multiple testing threshold of P < 0.0006. RESULTS: Women gained more weight than men (+6.5% vs +5.0%) but showed milder metabolic changes overall. Temporal sex differences were observed for C-reactive protein (women +5.1%, men +21.1%), glycine (women +5.2%, men +1.9%) and phenylalanine (women +0.6%, men +3.5%). In 566 individuals with ≥+3% weight gain vs 561 with weight change ≤-3%, divergent patterns were observed for insulin (+24% vs -10%), very-low-density-lipoprotein triglycerides (+32% vs -6%), high-density-lipoprotein2 cholesterol (-6.5% vs +4.7%), isoleucine (+5.7% vs -6.0%) and C-reactive protein (+25% vs -22%). CONCLUSION: We report absolute and proportional trends for 236 metabolic measures as new reference material for overall age-associated and specific weight-driven changes in real-world populations.

Do cobalt or chromium accumulate in metal-on-metal hip arthroplasty patients who have mild, moderate, or severe renal insufficiency?

AIMS: To find out if there is an inverse association between estimated glomerular filtration rate (eGFR) and whole blood cobalt (Co) and chromium (Cr) levels in patients with metal-on-metal (MoM) hip arthroplasties and renal insufficiency, suggesting that renal insufficiency could cause accumulation of Co and Cr in blood. METHODS: Out of 2,520 patients with 3,013 MoM hip arthroplasties, we identified 1,244 patients with whole blood Co, Cr, and creatinine measured within no more than a one-year interval. We analyzed the correlation of blood metal ion levels and eGFR to identify a potential trend of accumulating Co or Cr with decreasing eGFR. RESULTS: Of the 1,244 patients, 112 had normal renal function (eGFR > 90 ml/min/1.73 m2), 715 had mild renal insufficiency (eGFR 60 to 89), 384 had moderate renal insufficiency (eGFR 30 to 59), 27 had severe renal insufficiency (eGFR 15 to 29), and six had end-stage renal insufficiency (eGFR < 15). Median eGFR was 68 ml/min/1.73 m2 (interquartile range (IQR) 56 to 82), median whole blood Co was 3.3 µg/l (IQR 1.1 to 9.9), and median Cr was 2.0 µg/l (IQR 1.2 to 3.6). We did not observe an association between decreased eGFR and increased whole blood Co and Cr concentrations, but instead both increased Co and Cr were associated with higher eGFR, indicating better kidney function. CONCLUSION: As patients with MoM hip arthroplasties get older, the prevalence of renal insufficiency among them will increase, and orthopaedic surgeons will increasingly have to evaluate whether or not this affects patient follow-up. The USA Food and Drug Administration suggests that closer follow-up may be needed for MoM patients with renal insufficiency. We did not observe accumulation of blood Co or Cr in MoM hip arthroplasty patients with mild to severe renal insufficiency. Cite this article: Bone Joint J 2021;103-B(7):1231-1237.

A longitudinal analysis of COVID-19 lockdown stringency on sleep and resting heart rate measures across 20 countries.

Lockdowns imposed to stem the spread of COVID-19 massively disrupted the daily routines of many worldwide, but studies to date have been mostly confined to observations within a limited number of countries, based on subjective reports and surveys from specific time periods during the pandemic. We investigated associations between lockdown stringency and objective sleep and resting-heart rate measures in ~ 113,000 users of a consumer sleep tracker across 20 countries from Jan to Jul 2020, compared to an equivalent period in 2019. With stricter lockdown measures, midsleep times were universally delayed, particularly on weekdays, while midsleep variability and resting heart rate declined. These shifts (midsleep: + 0.09 to + 0.58 h; midsleep variability: - 0.12 to - 0.26 h; resting heart rate: - 0.35 to - 2.08 bpm) correlated with the severity of lockdown across different countries (all Ps < 0.001) and highlight the graded influence of stringency lockdowns on human physiology.

Whole blood chromium concentration is very rarely elevated independently of whole blood cobalt.

Due to the risk of adverse reactions to metal debris resulting from increased wear of the arthroplasty more than one million metal-on-metal (MoM) hip replacements worldwide are in active follow-up. Follow-up usually includes measurement of both whole blood cobalt (Co) and chromium (Cr) concentrations. Our experience is that Cr is seldom independently elevated. We wanted to ascertain whether blood Cr measurements could be omitted from follow-up protocols without lowering the quality of follow-up. We identified 8438 whole blood Co and Cr measurements performed without or prior to revision surgery. When the cut-off levels 5 µg/L and 7 µg/L were used, Cr was independently elevated in only 0.5% (95% confidence interval, CI, 0.3 to 0.6) and 0.2% (CI 0.1 to 0.3) of the measurements. The models with continuous variables showed that the higher the blood metal concentrations are the lower the percentage of measurements with Cr higher than Co. Our results suggest that whole blood Cr is very rarely independently elevated and therefore the authorities should consider omitting Cr measurements from their screening guidelines of MoM hip replacements. We believe this change in practice would simplify follow-up and lead to cost savings without decreasing the quality of follow-up.

EpiMetal: an open-source graphical web browser tool for easy statistical analyses in epidemiology and metabolomics.

MOTIVATION: An intuitive graphical interface that allows statistical analyses and visualizations of extensive data without any knowledge of dedicated statistical software or programming. IMPLEMENTATION: EpiMetal is a single-page web application written in JavaScript, to be used via a modern desktop web browser. GENERAL FEATURES: Standard epidemiological analyses and self-organizing maps for data-driven metabolic profiling are included. Multiple extensive datasets with an arbitrary number of continuous and category variables can be integrated with the software. Any snapshot of the analyses can be saved and shared with others via a www-link. We demonstrate the usage of EpiMetal using pilot data with over 500 quantitative molecular measures for each sample as well as in two large-scale epidemiological cohorts (N >10 000). AVAILABILITY: The software usage exemplar and the pilot data are open access online at [http://EpiMetal.computationalmedicine.fi]. MIT licensed source code is available at the Github repository at [https://github.com/amergin/epimetal].

Direct Estimation of HDL-Mediated Cholesterol Efflux Capacity from Serum.

BACKGROUND: HDL-mediated cholesterol efflux capacity (HDL-CEC) is a functional attribute that may have a protective role in atherogenesis. However, the estimation of HDL-CEC is based on in vitro cell assays that are laborious and hamper large-scale phenotyping. METHODS: Here, we present a cost-effective high-throughput nuclear magnetic resonance (NMR) spectroscopy method to estimate HDL-CEC directly from serum. We applied the new method in a population-based study of 7603 individuals including 574 who developed incident coronary heart disease (CHD) during 15 years of follow-up, making this the largest quantitative study for HDL-CEC. RESULTS: As estimated by NMR-spectroscopy, a 1-SD higher HDL-CEC was associated with a lower risk of incident CHD (hazards ratio, 0.86; 95%CI, 0.79-0.93, adjusted for traditional risk factors and HDL-C). These findings are consistent with published associations based on in vitro cell assays. CONCLUSIONS: These corroborative large-scale findings provide further support for a potential protective role of HDL-CEC in CHD and substantiate this new method and its future applications.

Postexercise recovery of the spatial QRS/T angle as a predictor of sudden cardiac death.

BACKGROUND: Postexercise measurement of heart rate (HR) recovery and QT interval dynamics provides prognostic information in various patient populations. OBJECTIVE: The purpose of this study was to assess whether the measurement of the spatial relationship between the depolarization and repolarization wavefronts (total cosine R-to-T [TCRT]) during the postexercise recovery phase would yield prognostic information. METHODS: The population consisted of 1297 patients (56 ± 13 years; 67% men) who performed a clinically indicated bicycle stress test. The exercise-recovery hysteresis of TCRT was quantified from the 12-lead exercise electrocardiogram by measuring the TCRT/HR loop area bounded by the exercise and first 3-minute postexercise recovery curves. The HR-corrected TCRT/HR hysteresis was calculated by dividing the area with the HR decrement during the first 3 minutes of recovery. HR recovery was measured at 1 minute postexercise recovery. End points were cardiac death and sudden cardiac death. RESULTS: During an average follow-up of 45 ± 12 months, 74 patients died (5.7%); 35 (2.6%) were cardiac deaths and 24 (1.9%) were sudden cardiac deaths. Reduced TCRT/HR loop area and TCRT/HR hysteresis were associated with cardiac mortality (P <.001). After adjustments for clinical variables, including ejection fraction, TCRT/HR loop area remained an independent predictor of cardiac death (hazard ratio 5.6; 95% confidence interval 1.6-19.1; P = .007) and sudden cardiac death (10.7; 95% confidence interval 1.4-83.7; P = .024). HR recovery did not remain a significant predictor in the multivariate analysis. CONCLUSIONS: Attenuated hysteresis of the depolarization and repolarization wavefronts during postexercise recovery is associated with an increased risk of cardiac and sudden cardiac death. Analysis of repolarization dynamics from exercise electrocardiogram represents a promising tool for risk stratification.

QRS-T morphology measured from exercise electrocardiogram as a predictor of cardiac mortality.

AIMS: Total cosine R-to-T (TCRT) measured from the standard 12-lead electrocardiogram (ECG) reflects the spatial relationship between depolarization and repolarization wavefronts and a low TCRT value is a marker of poor prognosis. We tested the hypothesis that measurement of TCRT or QRS/T angle from exercise ECG would provide even more powerful prognostic information. METHODS AND RESULTS: The prognostic significances of TCRT and QRS/T angle were assessed from exercise ECG recordings in 1297 patients [age 56 ± 13 years (mean ± SD), 67% males] undergoing a clinically indicated bicycle stress-test and the subsequent follow-up. During an average follow-up of 45 ± 12 months, 74 patients died (5.7%); 34 (2.6%) were cardiac deaths, and 24 (1.9%) were sudden cardiac deaths. Total cosine R-to-T and QRS/T angle exhibited a correlation with the RR intervals in the total cohort, but the individual responses were variable, e.g. median correlation of TCRT-RR was 0.89 with an inter-quartile range from 0.55 to 0.98. A reduced correlation of TCRT-RR during the recovery phase of exercise ECG predicted cardiac death [adjusted heart rate (HR) 3.5, 95% confidence interval (CI): 1.8-6.8, P= 0.001] similarly as the baseline TCRT measured from ECG at rest (adjusted HR 3.4, 95% CI: 1.4-8.1, P= 0.01). The poor correlation between the TCRT-RR both during the exercise and recovery was specifically related to a risk of sudden cardiac death (adjusted HR 6.2, 95% CI: 2.1-17.8, P< 0.001). CONCLUSIONS: Loss of rate-adaptation of the spatial relationship between depolarization and repolarization wavefronts is a strong predictor of cardiac death, especially of sudden cardiac death.

Dynamics and rate-dependence of the spatial angle between ventricular depolarization and repolarization wave fronts during exercise ECG.

BACKGROUND: QRS/T angle and the cosine of the angle between QRS and T-wave vectors (TCRT), measured from standard 12-lead electrocardiogram (ECG), have been used in risk stratification of patients. This study assessed the possible rate dependence of these variables during exercise ECG in healthy subjects. METHODS: Forty healthy volunteers, 20 men and 20 women, aged 34.6 +/- 3.4, underwent an exercise ECG testing. Twelve-lead ECG was recorded from each test subject and the spatial QRS/T angle and TCRT were automatically analyzed in a beat-to-beat manner with custom-made software. The individual TCRT/RR and QRST/RR patterns were fitted with seven different regression models, including a linear model and six nonlinear models. RESULTS: TCRT and QRS/T angle showed a significant rate dependence, with decreased values at higher heart rates (HR). In individual subjects, the second-degree polynomic model was the best regression model for TCRT/RR and QRST/RR slopes. It provided the best fit for both exercise and recovery. The overall TCRT/RR and QRST/RR slopes were similar between men and women during exercise and recovery. However, women had predominantly higher TCRT and QRS/T values. With respect to time, the dynamics of TCRT differed significantly between men and women; with a steeper exercise slope in women (women, -0.04/min vs -0.02/min in men, P < 0.0001). In addition, evident hysteresis was observed in the TCRT/RR slopes; with higher TCRT values during exercise. CONCLUSIONS: The individual patterns of TCRT and QRS/T angle are affected by HR and gender. Delayed rate adaptation creates hysteresis in the TCRT/RR slopes.

Electrocardiographic abnormalities and ventricular tachyarrhythmias after myocardial infarction.

AIMS: To assess the association of electrocardiographic repolarization and depolarization patterns to vulnerability to ventricular tachyarrhythmias. METHODS: In the present case-control study, a 12-lead ECG, signal-averaged ECG (SAECG), T-wave and QRS morphology, and T-wave alternans (TWA) were analyzed in post-MI patients with and without documented sustained ventricular tachycardia (VT) or fibrillation (VF) (VT/VF group, n=40, Non-VT/VF group, n=37, respectively) and healthy subjects (n=41). RESULTS: The QRS complex duration, measured from standard ECG (128 +/- 32 ms vs. 102 +/- 21 ms, p<0.001) or SAECG (125 +/- 25 ms vs. 99 +/- 20 ms, p<0.001), was significantly longer in the VT/VF than Non-VT/VF group. Several T-wave morphology variables, e.g., the total cosine of the angle between the main vectors of T-wave and QRS loops (TCRT), were different in the VT/VF (-0.13 +/- 0.58) and Non-VT/VF group (-0.11 +/- 0.48) compared to the healthy controls (0.47 +/- 0.50, p<0.001). However, there were no significant differences in any of the T-wave morphology variables including TWA between the two post-MI groups. CONCLUSION: Abnormalities in ventricular depolarization are more common among post-MI patients with prior VT/VF than in those without documented ventricular tachyarrhythmias. Abnormal T-wave morphology and TWA seem to reflect the heart disease rather than specifically vulnerability to VT/VF.

New Vectorcardiographic non-planarity measure of T-wave loop improves separation between healthy subjects and myocardial infarction patients.

Principal component analysis of vectorcardio-graphic T-wave loop has been shown to be a potential tool to describe the abnormality of the cardiac repolarization and to predict cardiac events in patients with cardiac disease. In this paper a new method for estimating the non-planarity of the T-wave loop is introduced and tested with healthy subjects and subjects with anterior or inferior myocardial infarction. The method is based on the resamping of T-wave data points with respect to the arc-length, the total least squares plane fitting, the identifying and reordering of the fitted axes, and decomposing the optimal rotation matrix. A recently published related measure, PCA3, was used for comparison purposes. The results showed that the non-planarity of T-wave loop increased significantly in patients with myocardial infarction compared to the healthy group. The new method separated healthy and patient groups with p-value 0.002 while PCA3 only with p-value 0.075. The new method was superior to PCA3 in separating the healthy patients from both infarction types.

T-Wave morphology in short QT syndrome.

BACKGROUND: Short QT syndrome (SQTS) is an inherited disorder characterized by a short QT interval and vulnerability to ventricular tachyarrhythmias. The diagnostic criteria for this syndrome are not well defined, since there is uncertainty about the lowest normal limits for the corrected QT (QTc) interval. OBJECTIVE: The aim of this study was to determine whether T-wave morphology parameters are abnormal in short QT subjects and whether those parameters can help in the diagnosis of SQTS. METHODS AND RESULTS: We describe three families (10 patients) with short QT intervals (QTc 310 +/- 32 ms). Seven subjects had suffered serious arrhythmic events and three were asymptomatic. T-wave morphology was assessed using the principal component analysis (PCA). QTc was significantly shorter and T-wave amplitude in lead V2 higher in the short QT subjects compared to healthy controls (n=149), (P < 0.001 for both). The total cosine of the angle between the main vectors of the QRS and T-wave loops (TCRT) was markedly abnormal among the symptomatic patients with short QT syndrome (n=7) (TCRT -0.14 +/- 0.55 vs 0.36 +/- 0.51, P=0.019). None of the three asymptomatic patients with short QT but without a history of arrhythmic events had an abnormally low TCRT. CONCLUSION: Our observations suggest that patients with a short QT interval and a history of arrhythmic events have abnormal T-wave loop parameters. These electrocardiogram (ECG) features may help in the diagnosis of SQTS in addition to the measurement of the duration of QT interval from the 12-lead ECG.

Influence of size and location of myocardial infarction on TCRT parameter: a computer simulation study.

Electrocardiographic (ECG) parameter ;total cosine R-to-T' (TCRT) has been shown to have remarkable prognostic value as a predictor of the outcomes of the coronary artery disease and the postmyocardial infarction patients. In this study, equivalent double layer (EDL) model was used to find action potential based causes to explain the observed diminution of the TCRT after myocardial infarction (MI). The model parameters affected the characteristics of QRS complex, ST segment and T wave. The size and the location of the MI were included in the model. The simulation results indicate that location of the infarction affects TCRT significantly. The trend, constituted by TCRT as function of the severity of the damage, differed significantly between the anterior and the inferior MI models. The values of the TCRT were lower in the case of anterior MI. Patient data (n=53) were used to confirm the results of the simulation: TCRT separated the anterior MI and inferior MI clearly (p<0.001). TCRT turned into negative values only in case of anterior MI. The results indicate that the location of the MI should be considered when interpreting changes of TCRT values with MI patients.

Influence of paper electrocardiogram digitizing on T wave and QRS complex morphology parameters.

BACKGROUND: Many morphological parameters of the electrocardiogram (ECG) can be calculated from a digital ECG and paper prints of ECG after digitizing. However, the digitizing process, including printing, scanning, ECG contour extraction, and alignment, can produce changes to the signals, reducing the reliability of some sensitive parameters of QRS complex and T wave. METHODS: The influence of the digitizing process on the parameters of T wave and QRS complex morphology was studied by comparing systematically the values of the nine ECG morphology parameters, computed from the digital ECG and the corresponding paper ECG. The robustness of the parameters to the digitizing process and their discrimination ability between healthy subjects and postinfarction patients were investigated. RESULTS: The standard T wave parameters and all selected dipolar loop-parameters retained their robustness and discrimination ability during the digitizing process of the paper ECGs. The non-dipolar parameters distorted strongly, especially those of the QRS complex. The T wave-based non-dipolar parameters retained their discrimination ability during the digitizing process. CONCLUSIONS: The selected standard T wave parameters and the dipolar loop-parameters calculated from properly digitized ECG paper prints can be utilized in patient studies. Non-dipolar parameters distort strongly but T wave-based parameters retain discriminatory information.

Functional significance of KCNH2 (HERG) K897T polymorphism for cardiac repolarization assessed by analysis of T-wave morphology.

BACKGROUND: Although KCNH2 (HERG) K897T polymorphism has been shown to be associated with the QT interval measured from 12-lead electrocardiogram (ECG), the functional significance of K897T polymorphism has been debated. The aim of this study was to test whether the K897T polymorphism of the KCNH2 (HERG) gene coding for the rapidly activating delayed rectifier K+ channel influences cardiac repolarization assessed by principal component analysis (PCA) of T-wave morphology. METHODS: Twelve-lead ECGs were digitized and T-wave morphology was analyzed with a PCA method in a population consisting of 228 healthy middle-aged subjects (121 women and 107 men). DNA samples were genotyped for the nucleotide 2690 A>C variation of the KCNH2 gene, corresponding to the KCNH2 K(lysine)897T(threonine) amino acid polymorphism. RESULTS: The allele frequencies were 0.86 (K) and 0.14 (T). The KCNH2 K897T polymorphism was associated with the total cosine R-to-T (TCRT), which reflects the wave front direction between depolarization and repolarization. TCRT was 0.421 in the genotype KK and 0.300 in the genotypes KT and TT (P = 0.04). The difference of TCRT was more marked between the KCNH2 K897T genotypes in women (P = 0.03) than in men (P = 0.52). CONCLUSIONS: The common K897T polymorphism of the cardiac potassium channel KCNH2 has functional significance for cardiac electrical properties. Subjects with a less common genotype, KT or TT, have smaller TCRT, which reflects dyssynchrony between depolarization and repolarization and is associated with an increased risk of cardiac mortality.

Usefulness of T-wave loop and QRS complex loop to predict mortality after acute myocardial infarction.

The aim of the study was to assess whether parameters based on the T-wave loop and QRS loop predict mortality, and cardiac mortality in particular, during follow-up of consecutive survivors of acute myocardial infarction (AMI). Patients with AMI (n = 437), treated according to contemporary guidelines, underwent digital high-resolution electrocardiography in orthogonal Frank leads (X, Y, Z) 5 to 14 days after AMI. Several T-wave and QRS loop parameters, such as the width and height of the loops and their ratio, T-wave loop dispersion (TWLD), QRS loop dispersion, and co-sine of the angle between the main vectors of the T-wave and QRS loops (TCRT), were calculated using a custom-made software package. During an average follow-up period of 43 +/- 14 months, 53 patients (12%) died. Of these 53 deaths, 35 were cardiac. TWLD and TCRT were the T-wave loop/QRS loop parameters that best predicted for cardiac mortality on univariate comparison (35.4 +/- 5.62 vs 32.8 +/- 2.87 for TWLD, p < 0.001 and -0.135 +/- 0.665 vs -0.657 +/- 0.518 for TCRT, p < 0.001, alive vs cardiac death, respectively). After adjustment for clinical risk markers in the Cox regression analysis, TWLD still significantly predicted for cardiac mortality (p < 0.05); however, TCRT had lost its predictive power. TWLD did not have significant univariate or multivariate association with noncardiac mortality. In conclusion, TWLD that describes the shape of the T-wave loop is a specific predictor of cardiac death and independent of the clinical risk markers in the current treatment era of patients with AMI.