Effects of a cool classroom microclimate on cardiac autonomic control and cognitive performances in undergraduate students.

An inverted U-shape relationship between cognitive performance and indoor temperature with best performance peaking at 21.6 °C was previously described. Little is known on classroom temperature reduction effects on cognitive performances and cardiac autonomic profile, during the cold season. Fifteen students underwent electrocardiogram recording during a lecture in two days in December when classroom temperatures were set as neutral (NEUTRAL, 20-22 °C) and cool (COOL, 16-18 °C). Cognitive performance (memory, verbal ability, reasoning, overall cognitive C-score) was assessed by Cambridge Brain Science cognitive evaluation tool. Cardiac autonomic control was evaluated via the analysis of spontaneous fluctuations of heart period, as the temporal distance between two successive R-wave peaks (RR). Spectral analysis provided the power in the high frequency (HF, 0.15-0.40 Hz) and low frequency (LF, 0.04-0.15 Hz) bands of RR variability. Sympatho-vagal interaction was assessed by LF to HF ratio (LF/HF). Symbolic analysis provided the fraction of RR patterns composed by three heart periods with no variation (0 V%) and two variations (2 V%), taken as markers of cardiac sympathetic and vagal modulations, respectively. The students' thermal comfort was assessed during NEUTRAL and COOL trials. Classroom temperatures were 21.5 ± 0.8 °C and 18.4 ± 0.4 °C during NEUTRAL and COOL. Memory, verbal ability, C-Score were greater during COOL (13.01 ± 3.43, 12.32 ± 2.58, 14.29 ± 2.90) compared to NEUTRAL (9.98 ± 2.26, p = 0.002; 8.57 ± 1.07, p = 0.001 and 10.35 ± 3.20, p = 0.001). LF/HF (2.4 ± 1.7) and 0 V% (23.2 ± 11.1%) were lower during COOL compared to NEUTRAL (3.7 ± 2.8, p = 0.042; 28.1 ± 12.2.1%, p = 0.031). During COOL, 2 V% was greater (30.5 ± 10.9%) compared to NEUTRAL (26.2 ± 11.3, p = 0.047). The students' thermal comfort was slightly reduced during COOL compared to NEUTRAL trial. During cold season, a better cognitive performance was obtained in a cooler indoor setting enabling therefore energy saving too.

Computerized automated algorithm-based analyses of digitized paper ECGs in Brugada syndrome.

BACKGROUND: Brugada syndrome is a rare inherited arrhythmic syndrome with a coved type 1 ST-segment elevation on ECG and an increased risk of sudden death. Many studies have evaluated risk stratification performance based on ECG-derived parameters. However, since historical Brugada patient cohorts included mostly paper ECGs, most studies have been based on manual ECG parameter measurements. We hypothesized that it would be possible to run automated algorithm-based analysis of paper ECGs. We aimed: 1) to validate the digitization process for paper ECGs in Brugada patients; and 2) to quantify the acute class I antiarrhythmic drug effect on relevant ECG parameters in Brugada syndrome. METHODS: A total of 176 patients (30% female, 43 ± 13 years old) with induced type 1 Brugada syndrome ECG were included in the study. All of the patients had paper ECGs before and during class I antiarrhythmic drug challenge. Twenty patients also had a digital ECG, in whom printouts were used to validate the digitization process. Paper ECGs were scanned and then digitized using ECGScan software, version 3.4.0 (AMPS, LLC, New York, NY, USA) to obtain FDA HL7 XML format ECGs. Measurements were automatically performed using the Bravo (AMPS, LLC, New York, NY, USA) and Glasgow algorithms. RESULTS: ECG parameters obtained from digital and digitized ECGs were closely correlated (r = 0.96 ± 0.07, R2 = 0.93 ± 0.12). Class I antiarrhythmic drugs significantly increased the global QRS duration (from 113 ± 20 to 138 ± 23, p < 0.0001). On lead V2, class I antiarrhythmic drugs increased ST-segment elevation (from 110 ± 84 to 338 ± 227 µV, p < 0.0001), decreased the ST slope (from 14.9 ± 23.3 to -27.4 ± 28.5, p < 0.0001) and increased the TpTe interval (from 88 ± 18 to 104 ± 33, p < 0.0001). CONCLUSIONS: Automated algorithm-based measurements of depolarization and repolarization parameters from digitized paper ECGs are reliable and could quantify the acute effects of class 1 antiarrhythmic drug challenge in Brugada patients. Our results support using computerized automated algorithm-based analyses from digitized paper ECGs to establish risk stratification decision trees in Brugada syndrome.

Association of thyroid-stimulating hormone with corrected QT interval variation: A prospective cohort study among patients with type 2 diabetes.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) have a prolonged QT interval and are at high risk of sudden cardiac death. A prolonged QT interval, indicative of impaired ventricular repolarization, is a risk factor for lethal ventricular arrhythmias, such as torsades-de-pointes (TdP). AIMS: To identify key clinical and biochemical covariates associated with Fridericia's corrected QT interval (QTcF) among euthyroid patients with T2DM, and to describe the temporal relationship between these factors and QTcF. METHODS: We performed prospective, clinical, biochemical and electrocardiographic measurements among patients with T2DM enrolled in the DIACART study at Pitié-Salpêtrière Hospital, at T1 (baseline) and T2 (follow-up), with a median interval of 2.55 years. RESULTS: Mean age (63.9±8.5 years), sex (22.35% women), drugs with known risk of TdP according to the CredibleMeds website (Cred-drugsTdP) and serum thyroid-stimulating hormone (TSH) concentrations correlated with QTcF in univariate analysis at both T1 and T2. In multivariable analysis, all these covariates except age were significantly associated with QTcF at both T1 (women: standardized ß=0.24±0.07, P=0.001; Cred-drugsTdP: ß=0.19±0.07, P=0.007; TSH concentration: ß=0.18±0.07, P=0.01) and T2 (women: ß=0.25±0.08, P=0.002; Cred-drugsTdP: ß=0.25±0.08, P=0.001; TSH concentration: ß=0.19±0.08, P=0.01). Furthermore, variation in QTcF over the years was associated with variation in TSH concentration (r=0.24, P=0.007) and changes in use of Cred-drugsTdP (r=0.2, P=0.02). CONCLUSIONS: Serum TSH concentration and its variation were associated with QTcF and its variation, even after correcting for the main determinants of QTcF. Interventional optimization of TSH concentration in T2DM warrants further investigation to establish its impact on the risk of TdP and sudden cardiac death.

Sex influences on ventricular repolarization duration in normal subjects and in type 1, 2 and 3 long QT syndrome patients: Different effect in acquired and congenital type 2 LQTS.

AIM: To evaluate the interaction between sex and rate corrected QT interval (QTc) duration in normal subjects after drug-induced QT prolongation and in LQTS patients. METHODS: Semi-automated measurements were performed on 875 digital ECGs (200 normal subjects off drugs (100 females), 200 normal subjects on Moxifloxacin (100 females), 259 LQT1 patients (161 females), 183 LQT2 patients (100 females) and 33 LQT3 patients (15 females)). A sex specific coefficient was calculated in each group and was used to calculate group specific corrected QT intervals (QTci). RESULTS: The mean sex difference (female minus male) in QTci interval duration was 17 ms 95%CI(12.7; 21.3) in normal subjects, 19 ms (14.5; 23.5) on Moxifloxacin, and 13 ms (4.8; 21.2) in LQT1 patients. The mean difference was 2 ms (-7.9; 11.9) in LQT2 and - 5 ms (-32.2; 22.2) in LQT3 patients (p = 0.0067 for the group and sex interaction). In the subgroup of patients above 15 years and without beta blocker treatment, the sex effect (female minus male) on QTci interval duration was 17 ms (4.1; 29.9) in LQT1 patients. QTc duration was not different between sex in LQT2 and in LQT3 patients (mean difference - 3 ms (-21.6; 15.6) and 12 ms (-28.4; 52.4), respectively) (p = 0.0191 for group and sex interaction). CONCLUSIONS: The interaction between sex and QTc interval is preserved in type 1 LQTS and drug-induced QTc prolongation but blurred in type 2 LQTS. Further experimental studies are warranted to better understand the interaction of sexual hormones with malfunctioning KCNH2 encoded repolarizing potassium channel.

Correction of QRS voltage for body mass index does not improve the prediction of fatal and nonfatal cardiovascular events. The Moli-sani study.

BACKGROUND AND AIMS: The diagnosis of LVH by ECG may particularly difficult in obese individuals. The aim of this study was to prospectively investigate whether the correction for body mass index (BMI) might improve the prognostic significance for cerebro and cardiovascular events of two electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH) in a large cohort of Italian adults. METHODS AND RESULTS: In 18,330 adults (54 ± 11 years, 55% women) from the Moli-sani cohort, obesity was defined using the ATPIII criteria. The Sokolow-Lyon (SL) and Cornell Voltage (CV) criteria were used for ECG-LVH. In overweight and obese subjects, as compared with normal weight, the prevalence of ECG-LVH by the SL index was lower. During follow-up (median 4.3 yrs), 503 cerebro and cardiovascular events occurred. One standard deviation (1-SD) increment in uncorrected and in BMI-corrected SL index and CV was associated with an increased risk of events (HR 1.12, 95% CI 1.02-1.22 and HR 1.16, 95% CI 1.06-1.26 and HR 1.12, 95% CI 1.03-1.23 and HR 1.17, 95% CI 1.07-1.27, respectively for SL and CV). In obese subjects, 1-SD increment in uncorrected CV and in BMI-corrected CV was not associated to a significant risk of events (HR 1.05, 95% CI 0.910-1.22 and HR 1.08, 95% CI 0.95-1.23 respectively). Uncorrected SL index showed a significant association with events, which was marginally stronger with BMI-corrected SL voltage (HR 1.18, 95% CI 1.02-1.37 and HR 1.17, 95% CI 1.04-1.33 respectively, Akaike information criterion change from 3220 to 3218). CONCLUSIONS: BMI correction of ECG LVH voltage criteria does not significantly improve the prediction of cerebro and cardiovascular events in obese patients in a large cohort at low cardiovascular risk.

Correction of the QRS duration for heart rate.

OBJECTIVE: To determine the clinical value of correcting the QRS duration for heart rate. BACKGROUND: We recently observed [1] that the QRS duration shortens during spontaneous increases in heart rate. In the current study, we analyzed ECG and pharmacokinetic data of 21 subjects who received quinidine in a recent study [2]. They experienced the expected post-quinidine increase in heart rate, allowing us to determine if quinidine's well-known QRS prolongation might be attenuated due to the concomitant rate increase. METHODS: In a crossover-designed study, after baseline ECG recording, the subjects received quinidine 400 mg orally or placebo, and ECGs and quinidine plasma concentrations were then obtained at 15 prespecified timepoints over 24 h. The previously determined QRS-RR regression slope (0.0125) [1] was used to rate-correct QRS. Change in QRS from baseline (dQRS) and rate-corrected change in QRS from baseline (dQRSc) over time were plotted with the mean quinidine concentration and the correlation of plasma concentration with dQRS and dQRSc was assessed by pairwise correlation and linear regression. RESULTS: There was a statistically significantly greater increase in heart rate at all timepoints combined in the quinidine arm compared with the placebo arm (9.9 ±â€¯6.80 vs. 5.2 ±â€¯7.42, respectively, p < 0.0001). dQRSc was significantly greater at all timepoints combined compared with dQRS (1.99 ±â€¯4.824 vs -0.68 ±â€¯4.640 msec, respectively, p < 0.0001). dQRS correlated poorly with quinidine plasma concentration (p = 0.127), with no clear change in QRS observed. On the other hand, dQRSc correlated well with quinidine concentration (p = 0.010), with a clear rise and fall in dQRSc that mirrored the rise and fall of quinidine concentration. CONCLUSION: Rate correction of the QRS duration improves detection of QRS prolongation in the presence of heart rate change. CONDENSED ABSTRACT: Using the mean QRS - RR slope determined previously in normal volunteers [1], we corrected the QRS duration for its known dependency on heart rate in 21 subjects who received quinidine and experienced the expected post-quinidine increase in heart rate in a recent clinical trial [2]. We found that uncorrected QRS did not correlate with quinidine concentration (p = 0.127), while rate-corrected QRS correlated well (p = 0.010) and mirrored the rise and fall of quinidine concentration. Rate correction of the QRS duration improves detection of QRS prolongation in the presence of heart rate change.

Population Prevalence and Correlates of Prolonged QT Interval: Cross-Sectional, Population-Based Study From Rural Uganda.

OBJECTIVES: We aimed to estimate the prevalence and correlates of QT interval prolongation in rural Uganda. BACKGROUND: Major electrocardiographic abnormalities, including prolonged QT interval, have been shown to be independently predictive of adverse cardiovascular events among Western populations. Cardiovascular diseases are on the rise in sub-Saharan Africa with poorly characterized context-specific risk factors. An important question is whether ECG screening might have value in cardiovascular disease risk stratification in SSA. METHODS: We conducted a cross-sectional survey in a sample of adults participating in an ongoing whole-population cohort in Mbarara, Uganda, in 2015. Of 1,814 subjects enrolled in the parent whole-population cohort, 856 (47%) participated in the study. Participants completed 12-lead electrocardiography and cardiovascular disease risk factors assessment. We summarized sex-specific, heart rate variation-adjusted QT (QTa) defining prolonged QTa as >460 ms in women and >450 ms in men. We fit linear and logistic regression models to estimate correlates of (continuous) QTa interval length and (dichotomous) prolonged QTa. Models included inverse probability of sampling weights to generate population-level estimates accounting for study nonparticipation. RESULTS: We assessed data from 828 participants with electrocardiograms. The weighted population mean age was 38.4 years (95% confidence interval: 36.3-40.4). The weighted population was 50.4% female, 11.5% had elevated blood pressure, and 57.6% had a high-sensitivity C-reactive protein >1 mg/dl. The population mean QTa was 409.1 ms (95% confidence interval: 405.1-413.1), and 10.3% (95% confidence interval: 7.8-13.5) met criteria for prolonged QTa. Women had a higher mean QTa (421.6 ms vs. 396.3 ms; p < 0.001), and a higher proportion of women had a prolonged QTa (14.0% vs. 9.3%; p = 0.122) than did men. In multivariable-adjusted regression models, female sex and hypertension correlated with higher mean QTa and meeting criteria for prolonged QTa, respectively. CONCLUSIONS: QT interval prolongation is highly prevalent in rural Uganda and may be more common than in high-income settings. Female sex, age, and high blood pressure correlated with QT interval prolongation. Future work should assess whether genetic predisposition or environmental factors in sub-Saharan African populations contribute to prolonged QT and clarify consequences.

Archiving and exchange of digital ECGs: A review of existing data formats.

Digital ECG is today a common practice but a universal format for its storage and exchange has never been widely implemented. The reason is linked on one side to the need of the manufacturing industry to (rightly) protect intellectual propriety and technology, but on the other to an inadequate effort of the research community to sufficiently enforce the use of digital ECG data. To some degree, and at least from a practical point of view, the problem is also linked to other factors, such as the need in some instances to protect patient-sensitive information, and whether digital exchanged data should also include annotations and measurements from an algorithm or by human intervention. As a result, after more than 30 years it is still common that the full ECG acquired information is not preserved, but only partially stored or saved as a PDF report. Paradoxically, the modern era of hospital information technology and the advent and large diffusion of electronic health record systems did not bring expected improvements: the process of digital ECG retrieval and management remains extremely complicated and cumbersome. The ultimate risk is that the ECG may end up being considered "just" an image rather than a voltage-versus-time signal as it has always been. A critical review of the most commonly used formats for digital ECG will be given, focusing in particular to those linked with DICOM, HL7 and SCP-ECG standards, and highlighting the respective advantages and limitations with special emphasis to the needs typically encountered by the research community. The goal is to provide a snapshot of the present, and to discuss mid- and long-term potential directions and changes, emphasizing what digital ECG organizations could do to "save" ECG information and facilitate its widespread exchange.

Comparison of automated interval measurements by widely used algorithms in digital electrocardiographs.

BACKGROUND: Automated measurements of electrocardiographic (ECG) intervals by current-generation digital electrocardiographs are critical to computer-based ECG diagnostic statements, to serial comparison of ECGs, and to epidemiological studies of ECG findings in populations. A previous study demonstrated generally small but often significant systematic differences among 4 algorithms widely used for automated ECG in the United States and that measurement differences could be related to the degree of abnormality of the underlying tracing. Since that publication, some algorithms have been adjusted, whereas other large manufacturers of automated ECGs have asked to participate in an extension of this comparison. METHODS: Seven widely used automated algorithms for computer-based interpretation participated in this blinded study of 800 digitized ECGs provided by the Cardiac Safety Research Consortium. All tracings were different from the study of 4 algorithms reported in 2014, and the selected population was heavily weighted toward groups with known effects on the QT interval: included were 200 normal subjects, 200 normal subjects receiving moxifloxacin as part of an active control arm of thorough QT studies, 200 subjects with genetically proved long QT syndrome type 1 (LQT1), and 200 subjects with genetically proved long QT syndrome Type 2 (LQT2). RESULTS: For the entire population of 800 subjects, pairwise differences between algorithms for each mean interval value were clinically small, even where statistically significant, ranging from 0.2 to 3.6milliseconds for the PR interval, 0.1 to 8.1milliseconds for QRS duration, and 0.1 to 9.3milliseconds for QT interval. The mean value of all paired differences among algorithms was higher in the long QT groups than in normals for both QRS duration and QT intervals. Differences in mean QRS duration ranged from 0.2 to 13.3milliseconds in the LQT1 subjects and from 0.2 to 11.0milliseconds in the LQT2 subjects. Differences in measured QT duration (not corrected for heart rate) ranged from 0.2 to 10.5milliseconds in the LQT1 subjects and from 0.9 to 12.8milliseconds in the LQT2 subjects. CONCLUSIONS: Among current-generation computer-based electrocardiographs, clinically small but statistically significant differences exist between ECG interval measurements by individual algorithms. Measurement differences between algorithms for QRS duration and for QT interval are larger in long QT interval subjects than in normal subjects. Comparisons of population study norms should be aware of small systematic differences in interval measurements due to different algorithm methodologies, within-individual interval measurement comparisons should use comparable methods, and further attempts to harmonize interval measurement methodologies are warranted.

An evaluation of multiple algorithms for the measurement of the heart rate corrected JTpeak interval.

Interest in the effects of drugs on the heart rate-corrected JTpeak (JTpc) interval from the body-surface ECG has spawned an increasing number of scientific investigations in the field of regulatory sciences, and more specifically in the context of the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative. We conducted a novel initiative to evaluate the role of automatic JTpc measurement technologies by comparing their ability to distinguish multi- from single-channel blocking drugs. A set of 5232 ECGs was shared by the FDA (through the Telemetric and Holter ECG Warehouse) with 3 ECG device companies (AMPS, Mortara, and Philips). We evaluated the differences in drug-concentration effects on these measurements between the commercial and the FDA technologies. We provide a description of the drug-induced placebo-corrected changes from baseline for dofetilide, quinidine, ranolazine, and verapamil, and discuss the various differences across all technologies. The results revealed only small differences between measurement technologies evaluated in this study. It also confirms that, in this dataset, the JTpc interval distinguishes between multi- and single-channel (hERG) blocking drugs when evaluating the effects of dofetilide, quinidine, ranolazine, and verapamil. However, in the case of quinidine and dofetilide, we noticed a poor consistency across technologies because of the lack of standard definitions for the location of the peak of the T-wave (T-apex) when the T-wave morphology is abnormal.

Frontal plane T-wave axis orientation predicts coronary events: Findings from the Moli-sani study.

BACKGROUND AND AIMS: The orientation of the frontal plane T-wave axis (T axis) is a reliable measure of ventricular repolarisation. We investigated the association between T-axis and the risk of coronary heart disease (CHD), heart failure (HF), atrial fibrillation (AF), stroke and cardiovascular (CVD) mortality. METHODS: A sample of 21,287 Moli-sani participants randomly recruited from the general adult (≥35 y) Italian population, free of CVD disease, were followed for a median of 4.4 years. T-axis was measured from a standard 12-lead resting ECG. RESULTS: After adjusting for CVD risk factors, subjects with abnormal T-axis showed an increase in the risk of both CHD (Hazard Ratio (HR) = 2.65; 95% CI = 1.67-4.21), HF (HR = 2.56; 1.80-3.63), AF (HR = 2.48; 1.56-3.94) and CVD mortality (HR = 2.83; 1.50-5.32). The association with CHD and HF, but not with AF or CVD death, remained significant after further adjustment for ECG abnormalities. Subjects with abnormal T-axis showed higher levels of subclinical inflammation, hs-troponin I and hs-NT-proBNP (p < 0.001 for all). However, further adjustment for troponin I and/or NT-proBNP determined a reduction of HRs ranging from 12.1 to 24.0% for CHD, while additional adjustment for inflammation markers did not change any association. CONCLUSIONS: An abnormal T-axis orientation is associated with an increased risk of both CHD and HF, independently of common CVD risk factors and other ECG abnormalities. This association was partially explained by increased hs-troponin I and hs-NT-proBNP levels.

Automated JTpeak analysis by BRAVO.

Using BRAVO algorithm (AMPS-LLC, NY, v4.4.0), 5223 ECGs from a publicly available annotated dataset from a randomized clinical trial on four different compounds and placebo were analyzed. ECGs were automatically processed and JTp interval was computed on: 12 standard ECG leads, Vector Magnitude (VM), and root mean square (RMS) leads. On VM and RMS, JTp intervals were nearly identical (228 ± 29 vs. 227 ± 30 ms respectively, with correlation of 0.99, p < 0.0001). On lead II, JTp interval was about 10 ms longer, but highly correlated with that measured on VM (0.94, p < 0.0001). Similarly, on lead V5, JTp was about 8 ms longer than on VM, with a correlation of 0.95, p < 0.0001. When compared to the public available annotations, JTp by BRAVO generated longer (about 8 ms) measurement and evidenced outliers conducible to both the T-wave peak (in few ECGs presenting notched shapes) and, to a lesser degree, to the J point, due to variability of the two algorithms. Differences on the drug-induced effect from the four compounds were negligible.

PDF-ECG in clinical practice: A model for long-term preservation of digital 12-lead ECG data.

BACKGROUND: In clinical practice, data archiving of resting 12-lead electrocardiograms (ECGs) is mainly achieved by storing a PDF report in the hospital electronic health record (EHR). When available, digital ECG source data (raw samples) are only retained within the ECG management system. OBJECTIVE: The widespread availability of the ECG source data would undoubtedly permit successive analysis and facilitate longitudinal studies, with both scientific and diagnostic benefits. METHODS & RESULTS: PDF-ECG is a hybrid archival format which allows to store in the same file both the standard graphical report of an ECG together with its source ECG data (waveforms). Using PDF-ECG as a model to address the challenge of ECG data portability, long-term archiving and documentation, a real-world proof-of-concept test was conducted in a northern Italy hospital. A set of volunteers undertook a basic ECG using routine hospital equipment and the source data captured. Using dedicated web services, PDF-ECG documents were then generated and seamlessly uploaded in the hospital EHR, replacing the standard PDF reports automatically generated at the time of acquisition. Finally, the PDF-ECG files could be successfully retrieved and re-analyzed. CONCLUSION: Adding PDF-ECG to an existing EHR had a minimal impact on the hospital's workflow, while preserving the ECG digital data.

Fast, accurate and easy-to-teach QT interval assessment: The triplicate concatenation method.

BACKGROUND: The gold standard method for assessing the QTcF (QT corrected for heart rate by Fridericia's cube root formula) interval is the "QTcF semiautomated triplicate averaging method" (TAM), which consists of measuring three QTcF values semiautomatically, for each 10-second sequence of a triplicate electrocardiogram set, and averaging them to get a global and unique QTcF value. Thus, TAM is time consuming. We have developed a new method, namely the "QTcF semiautomated triplicate concatenation method" (TCM), which consists of concatenating the three 10-second sequences of the triplicate electrocardiogram set as if they were a single 30-second electrocardiogram, and measuring QTcF only once for the triplicate electrocardiogram set. AIM: To compare the TCM method with the TAM method. METHODS: Fifty triplicate electrocardiograms were read twice by an expert and a student using both methods (TAM and TCM). We plotted Bland-Altman plots to assess agreement between the two methods, and to compare the student and expert results. The time needed to read a set of 20 consecutive triplicate electrocardiograms was measured. RESULTS: Limits of agreement between TAM and TCM ranged from -8.25 to 6.75ms with the expert reader. TCM was twice as fast as TAM (17.38 versus 34.28min for 20 consecutive triplicate electrocardiograms). Bland-Altman plots comparing student and expert results showed limits of agreement ranging from -4.34 to 11.75ms for TAM, and -1.2 to 8.0ms for TCM. CONCLUSIONS: TAM and TCM show good agreement for QT measurement. TCM is less time consuming than TAM. After a learning session, an inexperienced reader can measure the QT interval accurately with both methods.

Obesity and ECG left ventricular hypertrophy.

AIM: Our aim was to investigate the prevalence and the prognostic significance for fatal and nonfatal cerebrovascular and cardiovascular events of different ECG criteria for left ventricular hypertrophy (LVH) in normal weight, overweight and obese patients in an adult Italian population. METHODS: A total of 18 330 adults (mean age 54 ±â€Š11 years, 55% women, 53% hypertensive patients) were analyzed from the Moli-sani cohort. Obesity was defined using the ATPIII criteria. ECG-LVH was defined according to 2013 ESC-ESH guidelines. RESULTS: The age and sex adjusted prevalence of ECG-LVH did not differ from normal weight patients to class 1-3 obesity patients, when Cornell-voltage criterion was used. In overweight and obese patients, as compared with normal weight patients, a progressively lower prevalence of ECG-LVH was observed when the Sokolow-Lyon index was used, whereas a higher prevalence was shown by using the aVL R-wave voltage (>11 and >5.7 mm) and the Cornell-voltage-QRS duration product. The incidence of cardiovascular events was significantly greater in patients with ECG LVH diagnosis by the Cornell voltage [hazard ratio 1.89, 95% confidence interval (CI) 1.05-3.39] and the Cornell product (hazard ratio 1.87, 95% CI 1.31-2.67). After adjusting for different confounders (age, sex, cigarette, hypertension, hypercholesterolemia, diabetes, income, education, occupational class and physical activity) and for BMI categories, only the Cornell product remained significantly associated with a higher incidence of cardiovascular events (hazard ratio 1.66; 95% CI 1.16-2.38). The predictive significance of different LVH criteria was assessed across BMI categories; after adjusting for confounders, no LVH criteria were significantly associated with an increased risk of cardiovascular events in obese patients; Cornell-product LVH remained an independent predictor of events in normal weight and overweight individuals (hazard ratio 2.63; 95% CI 1.10-6.28 and hazard ratio 2.72; 95% CI 1.52-4.25, respectively). CONCLUSION: Our results confirm that ECG LVH prevalence may differ according to the criteria used across BMI categories in a low cardiovascular risk cohort. The use of different LVH criteria according to BMI categories may improve cardiovascular risk stratification in a general population independently of several confounding factors.

A fundamental relationship between intraventricular conduction and heart rate.

BACKGROUND: Existence of a relationship between the electrocardiographic QRS interval duration and the diurnally varying heart rate, of consistent sign and magnitude, is controversial and the relationship has not been fully characterized in normal populations. METHODS AND RESULTS: We analyzed the QRS-RR interval relationship in 884 Holter recordings in 410 normal subjects participating in 5 clinical trials. The slope of the linear regression of QRS on RR was positive in 93% of subjects with an average slope of 0.0125, which indicates an increase in QRS duration of 1.25msec for an increase in RR interval of 100msec. The increase was 15% larger in women than in men. Age had no significant effect on the slope. CONCLUSIONS: In two populations of normal subjects we observed a robust, direct relationship between the spontaneously changing RR interval and intraventricular conduction time represented by the duration of the QRS interval. As heart rate increases, QRS duration decreases. The change is larger in women. These observations have important physiological and clinical implications.

T-wave axis deviation is associated with biomarkers of low-grade inflammation. Findings from the MOLI-SANI study.

T-wave axis deviation (TDev) may help identifying subjects at risk for major cardiac events and mortality, but the pathogenesis of TDev is not well established; in particular, the possible association between TDev and inflammation is unexplored and unknown. We aimed at investigating the association between low-grade inflammation and TDev abnormalities by conducting a cross-sectional analysis on 17,507 subjects apparently free from coronary heart and haematological diseases enrolled in the MOLI-SANI study. TDev was measured from a standard 12-lead resting electrocardiogram. High sensitivity (Hs) C-reactive protein (CRP), leukocyte (WBC) and platelet counts, neutrophil or granulocyte to lymphocyte ratios were used as markers of inflammation. In multivariable model subjects reporting high CRP levels had higher odds of having borderline and abnormal TDev (OR=1.70; 95 %CI: 1.53-1.90 and OR=1.72; 95 %CI: 1.23-2.41, respectively); the association was still significant, although reduced, after controlling for body mass index (OR=1.17; 95 %CI: 1.05-1.32, for borderline and OR=1.46; 95 %CI: 1.03-2.08, for abnormal). Similarly, higher neutrophil or granulocyte to lymphocyte ratios were associated with increased odds of having abnormal TDev. Neither platelet nor leukocyte counts were associated with abnormal TDev. The relationship between CRP with TDev abnormalities was significantly stronger in men, in non- obese or normotensive individuals, and in those without metabolic syndrome. In conclusion, C-reactive protein and some cellular biomarkers of inflammation such as granulocyte or neutrophil to lymphocyte ratios were independently associated with abnormal TDev, especially in subjects at low CVD risk. These results suggest that a low-grade inflammation likely contributes to the pathogenesis of T- wave axis deviation.

T-wave axis deviation, metabolic syndrome and estimated cardiovascular risk--in men and women of the MOLI-SANI study.

AIM: We aimed at investigating the association between T-wave axis deviation, metabolic syndrome (MetS), its components and estimated risk of cardiovascular disease (CVD) at 10 years in an adult Italian population. METHODS: 11,143 women (54 ± 11 years) and 9742 men (55 ± 11 years) were analyzed from the Moli-sani cohort, randomly recruited from the general population. MetS was defined using the ATPIII criteria. T-wave axis deviation was measured from the standard 12-lead resting electrocardiogram. CVD risk in ten years was estimated by the CUORE score. RESULTS: 29% of men and 27% of women with MetS showed borderline or abnormal T-wave as compared to 24% and 17% without MetS (p < 0.0001 for both genders). Among components of MetS, elevated waist and blood pressure were strongly associated with T-wave axis deviation, whereas glucose, HDL and triglycerides were only marginally. The odds of having borderline or abnormal T-wave axis deviation in multivariable regression analysis, was 1.38 (95% CI:1.25-1.53) in MetS men and 1.68 (95% CI:1.51-1.87) in MetS women compared to those without. Further adjustment for MetS components completely abolished the associations. Abnormal T-wave axis deviation was associated with an increased risk of CVD in 10 years in men (OR = 4.4; 95% CI:1.10-17.9). CONCLUSION: T-wave axis deviation is strongly associated with components of the MetS, in particular high waist circumference and blood pressure and with an increased CVD risk, particularly in men. ECG monitoring to identify T-wave axis deviation in obese, hypertensive or MetS subjects can be an early indicator of vascular disease and help in reducing cardiac events.

T-wave axis deviation, metabolic syndrome and cardiovascular risk: results from the MOLI-SANI study.

Early recognition of patients at increased cardiovascular risk is a major challenge. The surface electrocardiogram provides a useful platform and it has been used to propose several indexes. T wave axis abnormality is associated with an increased risk of cardiovascular mortality, independently of other risk factors and can be associated with the presence of the metabolic syndrome (MetS). We assessed the prevalence of T axis abnormalities and its relationship with MetS and its components in a large population of Italian adults. Data concerning 11,143 women (54 ± 11 years) and 9742 men (55 ± 11 years) randomly recruited from a general population (Moli-sani cohort) were analyzed. After excluding subjects with incomplete data and with history of cardiac disease or left ventricular hypertrophy, T-wave axis was normal in 74.5% of men and 80.9% of women, borderline in 23.6% and 17.3% and abnormal in 1.9% and 1.8%. In subjects with MetS, the prevalence of borderline or abnormal T-wave axis deviation was higher than in subjects without MetS (in men: 26.6% vs. 22.1% and 2.5% vs. 1.7%; in women: 25% vs. 15% and 2.4% vs. 1.6%, respectively for borderline and abnormal levels, p<0.0001). Each component of MetS increased the odds of having borderline or abnormal T-wave axis deviation by 1.21 in men and 1.31 in women. T wave axis deviation is associated with MetS and its individual components. These findings confirm previous reported results, expanding them to a large and representative sample of European population of Caucasian ethnicity.

The time course of new T-wave ECG descriptors following single- and double-dose administration of sotalol in healthy subjects.

INTRODUCTION: The aim of the study was to assess the time course effect of IKr blockade on ECG biomarkers of ventricular repolarization and to evaluate the accuracy of a fully automatic approach for QT duration evaluation. METHODS: Twelve-lead digital ECG Holter was recorded in 38 healthy subjects (27 males, mean age = 27.4 + or - 8.0 years) on baseline conditions (day 0) and after administration of 160 mg (day 1) and 320 mg (day 2) of d-l sotalol. For each 24-hour period and each subject, ECGs were extracted every 10 minutes during the 4-hour period following drug dosage. Ventricular repolarization was characterized using three biomarker categories: conventional ECG time intervals, principal component analysis (PCA) analysis on the T wave, and fully automatic biomarkers computed from a mathematical model of the T wave. RESULTS: QT interval was significantly prolonged starting 1 hour 20 minutes after drug dosing with 160 mg and 1 hour 10 minutes after drug dosing with 320 mg. PCA ventricular repolarization parameters sotalol-induced changes were delayed (>3 hours). After sotalol dosing, the early phase of the T wave changed earlier than the late phase prolongation. Globally, the modeled surrogate QT paralleled manual QT changes. The duration of manual QT and automatic surrogate QT were strongly correlated (R(2) = 0.92, P < 0.001). The Bland and Altman plot revealed a nonstationary systematic bias (bias = 26.5 ms + or - 1.96*SD = 16 ms). CONCLUSIONS: Changes in different ECG biomarkers of ventricular repolarization display different kinetics after administration of a potent potassium channel blocker. These differences need to be taken into account when designing ventricular repolarization ECG studies.