Multiomics, virtual reality and artificial intelligence in heart failure.

Aim: Multiomics delivers more biological insight than targeted investigations. We applied multiomics to patients with heart failure (HF) and reduced ejection fraction (HFrEF), with machine learning applied to advanced ECG (AECG) and echocardiography artificial intelligence (Echo AI). Patients & methods: In total, 46 patients with HFrEF and 20 controls underwent metabolomic profiling, including liquid/gas chromatography-mass spectrometry and solid-phase microextraction volatilomics in plasma and urine. HFrEF was defined using left ventricular (LV) global longitudinal strain, EF and N-terminal pro hormone BNP. AECG and Echo AI were performed over 5 min, with a subset of patients undergoing a virtual reality mental stress test. Results: A-ECG had similar diagnostic accuracy as N-terminal pro hormone BNP for HFrEF (area under the curve = 0.95, 95% CI: 0.85-0.99), and correlated with global longitudinal strain (r = -0.77, p < 0.0001), while Echo AI-generated measurements correlated well with manually measured LV end diastolic volume r = 0.77, LV end systolic volume r = 0.8, LVEF r = 0.71, indexed left atrium volume r = 0.71 and indexed LV mass r = 0.6, p < 0.005. AI-LVEF and other HFrEF biomarkers had a similar discrimination for HFrEF (area under the curve AI-LVEF = 0.88; 95% CI: -0.03 to 0.15; p = 0.19). Virtual reality mental stress test elicited arrhythmic biomarkers on AECG and indicated blunted autonomic responsiveness (alpha 2 of RR interval variability, p = 1 × 10-4) in HFrEF. Conclusion: Multiomics-related machine learning shows promise for the assessment of HF.

Lay abstract Multiomics is the integration of multiple sources of health information, for example, genomic, metabolite, etc. This delivers more insight than targeted single investigations and provides an ability to perceive subtle individual differences between people. In this study we applied multiomics to patients with heart failure (HF) using DNA sequencing, metabolomics and machine learning applied to ECG echocardiography. We demonstrated significant differences between subsets of patients with HF using these methods. We also showed that machine learning has significant diagnostic potential in identifying HF patients more efficiently than manual or conventional techniques.

Evidence of cardiac electrical remodeling in patients with Huntington disease.

OBJECTIVE: Although Huntington's disease (HD) is a disease of the central nervous system, HD mortality surveys indicate heart disease as a major cause of death. Cardiac dysfunction in HD might be a primary consequence of peripherally expressed mutant huntingtin or secondary to either a general decline in health or the onset of neurological dysfunction. The aim of the study was to clarify the heart muscle involvement. MATERIALS AND METHODS: We measured conventional and advanced resting ECG indices. Thirty-one subjects with a confirmed huntingtin gene mutation and 31 age- and gender-matched controls were included. The HD subjects were divided into four groups based on their Unified Huntington Disease Rating Scale (UHDRS) motor score. RESULTS: We detected changes in advanced ECG variables connected with electrical ventricular remodeling (t test, p < 0.01). The increase in the unexplained part of both QT variability and the standard deviation of normal-to-normal QT intervals, presumably reflecting beat-to-beat changes in repolarization, was most pronounced. Further, both variables correlated with the product of the cytosine-adenine-guanine (CAG) triplets' repeat length and the subjects' age (CAP), the former R = 0.423 (p = 0.018) and the latter R = 0.499 (p = 0.004). There was no correlation between the CAP score and any of variables representing autonomic nervous system activity. CONCLUSIONS: Both autonomic nervous system dysfunction and cardiac electrical remodeling are present in patients with HD. The changes in advanced ECG variables observed in the study evolve with HD progression. The increased values of QT unexplained variability may be a marker of temporal inhomogeneity in ventricular repolarization associated with malignant ventricular arrhythmias.

Cardiovascular autonomic dysfunction and carotid stiffness in adults with repaired tetralogy of Fallot.

PURPOSE: Adults after surgical repair of tetralogy of Fallot (ToF) may have impaired vascular and cardiac autonomic function. Thus, we wanted to assess interrelations between heart rate variability (HRV) and heart rate recovery (HRR), as parameters of cardiac autonomic function, and arterial stiffness, as a parameter of vascular function, in adults with repaired ToF as compared to healthy controls. METHODS: In a case-control study of adults with repaired ToF and healthy age-matched controls we measured: 5-min HRV variability (with time and frequency domain data collected), carotid artery stiffness (through pulse-wave analysis using echo-tracking ultrasound) and post-exercise HRR (cycle ergometer exercise testing). RESULTS: Twenty-five patients with repaired ToF (mean age 38 ± 10 years) and 10 healthy controls (mean age 39 ± 8 years) were included. Selected HRR and HRV (time-domain) parameters, but not arterial stiffness were significantly reduced in adults after ToF repair. Moreover, a strong association between late/slow HRR (after 2, 3 and 4 min) and carotid artery stiffness was detected in ToF patients (r = -0.404, p = 0.045; r = -0.545, p = 0.005 and r = -0.545, p = 0.005, respectively), with statistical significance retained even after adjusting for age, gender, resting heart rate and ß-blockers use (r = -0.393, p = 0.024 for HRR after 3 min). CONCLUSION: Autonomic cardiac function is impaired in patients with repaired ToF, and independently associated with vascular function in adults after ToF repair, but not in age-matched healthy controls. These results might help in introducing new predictors of cardiovascular morbidity in a growing population of adults after surgical repair of ToF.

Delineation of QRS offset by instantaneous changes in ECG vector angle can improve detection of acute inferior myocardial infarctions.

We developed an automated new method for determining QRS offset, based on angular velocity (AV) changes around the QRS loop, and compared the method's performance to that of manual and more established automated methods for determining QRS offset in both healthy subjects and patients with acute myocardial infarction (AMI). Specifically, using Frank leads reconstructed from standard 12-lead ECGs, we determined AV in the direction of change raised to the 4th power, d(t). We found that the d(t)-determined AV transition (ΔAV) nearly coincided with manually determined QRS offset in healthy subjects, and in 27 patients with anterior AMI. However, in 31 patients with inferior AMI, ΔAV typically preceded that of QRS offset determined by the established automated methods, and by more than 10ms in 32% of cases. While this "ΔAV precedence" coincided with diagnostic ST elevation in only a minority of patients with recent inferior AMI, the use of ΔAV precedence as a complement to traditional determination of ST elevation increased the sensitivity for detecting inferior AMIs from 23 to 42%.

Heart rate-guided, but not dose-guided titration of beta blockers stabilizes ventricular repolarization in patients with chronic heart failure.

AIMS: We compared the effects of heart rate-guided and dose-guided beta-blocker titration strategies on QT variability in patients with chronic heart failure (CHF). METHODS: In a prospective study we recorded 5-minute resting high-resolution ECGs (HRECG) in 100 patients with CHF and measured heart rate (HR) and ventricular repolarization by QT variability index (QTVI). In a subgroup of patients not reaching target HR (<70bpm) we uptitrated beta blockers and repeated HRECG measurements 3months thereafter. RESULTS: Target HR was present in 46 patients (group A), and in 54 patients HR was above target (group B). The groups did not differ in age, gender, NYHA class, NT pro-BNP, creatinine, or beta blocker dose. Patients in group A displayed significantly lower QTVI than patients in group B (-1.25±0.55 vs. -1.52±0.42, P=0.013). When uptitrating beta-blockers we found a decrease in HR (from 91±15bpm to 71±15bpm, P<0.001), NTpro BNP levels (from 4474±3878pg/ml to 3042±2566pg/ml, P=0.024), and NYHA class (from 3.0±0.8 to 2.5±0.7, P=0.006). With beta-blocker uptitration QTVI decreased in 10 of 24 patients (42%). In these patients HR decreased more than in the remaining cohort (-25±20bpm vs. -15±17bpm, P=0.017). On multivariate analysis, the presence of target HR was a predictor of QTVI decrease (P=0.017), but beta-blocker dose was not. CONCLUSIONS: In patients with CHF treated by beta-blockers, changes in QT variability appear to occur in parallel with changes of heart rate. This suggests that heart rate-guided titration of beta-blockers may be associated with decreased risk of sudden cardiac death.

High resolution ECG-aided early prognostic model for comatose survivors of out of hospital cardiac arrest.

Out of hospital cardiac arrest (OHCA) has a high mortality despite modern treatment. Reliable early prognosis in OHCA could significantly improve clinical decision making. We explored prognostic utility of advanced ECG parameters, obtained from high-resolution ECG, in combination with clinical and OHCA-related parameters during treatment with mild induced hypothermia (MIH) and after rewarming in unconscious survivors of OHCA. Ninety-two patients during MIH and 66 after rewarming were included. During MIH, a score based on initial rhythm, QRS-upslope and systolic pressure resulted in an area under curve (AUC) of 0.82 and accuracy of 80% for survival. After rewarming, a score based on admission rhythm, sum of 12 lead QRS voltages, and mean lateral ST segment level in leads I and V6 resulted in an AUC of 0.88 and accuracy of 85% for survival. ECG can assist with early prognostication in unconscious survivors of OHCA during MIH and after rewarming.

The presence of electromechanical mismatch in nonischemic dilated cardiomyopathy is associated with ventricular repolarization instability.

BACKGROUND: We analyzed electromechanical mismatch (EMM) and its relationship to ventricular repolarization in patients with nonischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: In 39 DCM patients with left ventricular ejection fraction (LVEF) <40% and New York Heart Association functional class ≥III, electroanatomic mapping was used to quantify areas of EMM. High-resolution electrocardiograph was used to measure heart rate variability (HRV) and QT variability index (QTVI). EMM was present in 22 patients (56%, group 1), whereas 17 patients presented no mismatched segments (44%, group 2). The groups did not differ in age (56 ± 10 years in group 1 vs 57 ± 7 years in group 2; P = .82), sex (male: 82% vs 94%; P = .40), LVEF (27 ± 8% vs 25 ± 6%; P = .18), or N-terminal pro-B-type natriuretic peptide (2,350 pg/mL vs 2,831 pg/mL; P = .32). Although heart rate and HRV were similar in both groups (rate: 80 ± 20 beats/min in group 1 vs 74 ± 19 beats/min in group 2 [P = .47]; standard deviation of normal-to normal RR intervals: 106 ± 79 vs 88 ± 115 [P = .61]), we found significantly higher QTVI values in patients from group 1 (-1.15 ± 0.46 vs -1.62 ± 0.51 in group 2; P = .005). In patients with implantable cardioverter-defibrillators, ventricular arrhythmias recorded ≤1 year before enrollment were more frequent in group 1 than in group 2 (58% vs 13%; P = .02). CONCLUSIONS: EMM is present in a majority of patients with DCM and is associated with ventricular repolarization instability.

Predicting "heart age" using electrocardiography.

Knowledge of a patient's cardiac age, or "heart age", could prove useful to both patients and physicians for better encouraging lifestyle changes potentially beneficial for cardiovascular health. This may be particularly true for patients who exhibit symptoms but who test negative for cardiac pathology. We developed a statistical model, using a Bayesian approach, that predicts an individual's heart age based on his/her electrocardiogram (ECG). The model is tailored to healthy individuals, with no known risk factors, who are at least 20 years old and for whom a resting ~5 min 12-lead ECG has been obtained. We evaluated the model using a database of ECGs from 776 such individuals. Secondarily, we also applied the model to other groups of individuals who had received 5-min ECGs, including 221 with risk factors for cardiac disease, 441 with overt cardiac disease diagnosed by clinical imaging tests, and a smaller group of highly endurance-trained athletes. Model-related heart age predictions in healthy non-athletes tended to center around body age, whereas about three-fourths of the subjects with risk factors and nearly all patients with proven heart diseases had higher predicted heart ages than true body ages. The model also predicted somewhat higher heart ages than body ages in a majority of highly endurance-trained athletes, potentially consistent with possible fibrotic or other anomalies recently noted in such individuals.

Improved ECG pre-processing for beat-to-beat QT interval variability measurement.

The aim of this study was to enhance the ECG pre-processing modalities for beat-to-beat QT interval variability measurement based on template matching. The R-peak detection algorithm has been substituted and an efficient baseline removal algorithm has been implemented in existing computer software. To test performance we used simulated ECG data with fixed QT intervals featuring Gaussian noise, baseline wander and amplitude modulation and two alternative algorithms. We computed the standard deviation of beat-to-beat QT intervals as a marker of QT interval variability (QTV). Significantly a lower beat-to-beat QTV was found in the updated approach compared the original algorithm. In addition, the updated template matching computer software outperformed the previous version in discarding fewer beats. In conclusion, the updated ECG preprocessing algorithm is recommended for more accurate quantification of beat-to-beat QT interval variability.

Conventional QT variability measurement vs. template matching techniques: comparison of performance using simulated and real ECG.

Increased beat-to-beat variability in the QT interval (QTV) of ECG has been associated with increased risk for sudden cardiac death, but its measurement is technically challenging and currently not standardized. The aim of this study was to investigate the performance of commonly used beat-to-beat QT interval measurement algorithms. Three different methods (conventional, template stretching and template time shifting) were subjected to simulated data featuring typical ECG recording issues (broadband noise, baseline wander, amplitude modulation) and real short-term ECG of patients before and after infusion of sotalol, a QT interval prolonging drug. Among the three algorithms, the conventional algorithm was most susceptible to noise whereas the template time shifting algorithm showed superior overall performance on simulated and real ECG. None of the algorithms was able to detect increased beat-to-beat QT interval variability after sotalol infusion despite marked prolongation of the average QT interval. The QTV estimates of all three algorithms were inversely correlated with the amplitude of the T wave. In conclusion, template matching algorithms, in particular the time shifting algorithm, are recommended for beat-to-beat variability measurement of QT interval in body surface ECG. Recording noise, T wave amplitude and the beat-rejection strategy are important factors of QTV measurement and require further investigation.

Sedentary long-duration head-down bed rest and ECG repolarization heterogeneity.

BACKGROUND: We studied the effects of 90 d of 6 degrees head-down bed rest (HDBR) on cardiac autonomic and advanced electrocardiographic (ECC) function, especially on repolarization heterogeneity as assessed by beat-to-beat QT interval variability (QTV), T-wave complexity, and 3-dimensional ECG. Based on prior observations of lengthening of the QTc interval during long-duration spaceflight, we hypothesized that abnormalities in ECG repolarization would also occur during long-duration HDBR. METHODS: During controlled breathing, 5-min supine high-fidelity 12-lead ECGs were obtained from 20 healthy subjects (14 men and 6 women) together with measurements of plasma volume and electrolytes at 5 points in time: within 10 d before; 28-30, 60, and 90 d into; and 3-5 d after HDBR. RESULTS: By repeated measures ANOVA, 90 d of sedentary HDBR significantly increased the QTV index (from -1.87 +/- 0.33 to - 1.53 +/- 0.39 units), the index of unexplained QTV (from 0.61 +/- 0.48 to 1.21 +/- 0.40 units), the T-wave complexity intradipolar ratio (from 0.344 +/- 0.260 to 2.04 +/- 4.01%), and the spatial QRS-T angle (from 49.1 +/- 23.8 to 58.7 +/- 31.0 degrees), and significantly decreased the spatial ventricular gradient (from 91.3 +/- 26.5 to 59.1 +/- 23.0 mV x ms(-1)). These changes resolved in part by 3-5 d after resumption of ambulation, but unlike concomitant changes in the QTc interval itself and in heart rate variability, they did not significantly relate to changes in electrolytes or plasma volume. CONCLUSIONS: Sedentary, long-duration HDBR reversibly increases ECG repolarization heterogeneity and by inference ventricular arrhythmic risk.

Detection of hypertrophic cardiomyopathy is improved when using advanced rather than strictly conventional 12-lead electrocardiogram.

INTRODUCTION: Twelve-lead electrocardiogram (ECG) is used to screen for hypertrophic cardiomyopathy (HCM), but up to 25% of HCM patients do not have distinctly abnormal ECGs, whereas up to 5% to 15% of healthy athletes do. We hypothesized that an approximately 5-minute resting advanced 12-lead ECG test ("A-ECG score") could detect HCM with greater sensitivity than pooled conventional ECG criteria and distinguish healthy athletes from HCM with greater specificity. MATERIALS AND METHODS: Five-minute 12-lead ECGs were obtained from 56 HCM patients, 56 age/sex-matched healthy controls, and 69 younger endurance-trained athletes. Electrocardiograms were analyzed using recently suggested pooled conventional ECG criteria and also A-ECG scoring techniques that considered results from multiple advanced and conventional ECG parameters. RESULTS: Compared with pooled criteria from the strictly conventional ECG, an A-ECG logistic score incorporating results from just 3 advanced ECG parameters (spatial QRS-T angle, unexplained portion of QT variability, and T-wave principal component analysis ratio) increased the sensitivity of ECG for identifying HCM from 89% (78%-96%) to 98% (89%-100%; P = .025), while increasing specificity from 90% (83%-94%) to 95% (92%-99%; P = .020). CONCLUSIONS: Resting 12-lead A-ECG scores that are simultaneously more sensitive than pooled conventional ECG criteria for detecting HCM and more specific for distinguishing healthy athletes and other healthy controls from HCM can be constructed. Pending further prospective validation, such scores may lead to improved ECG-based screening for HCM.

Accuracy of advanced versus strictly conventional 12-lead ECG for detection and screening of coronary artery disease, left ventricular hypertrophy and left ventricular systolic dysfunction.

BACKGROUND: Resting conventional 12-lead ECG has low sensitivity for detection of coronary artery disease (CAD) and left ventricular hypertrophy (LVH) and low positive predictive value (PPV) for prediction of left ventricular systolic dysfunction (LVSD). We hypothesized that a approximately 5-min resting 12-lead advanced ECG test ("A-ECG") that combined results from both the advanced and conventional ECG could more accurately screen for these conditions than strictly conventional ECG. METHODS: Results from nearly every conventional and advanced resting ECG parameter known from the literature to have diagnostic or predictive value were first retrospectively evaluated in 418 healthy controls and 290 patients with imaging-proven CAD, LVH and/or LVSD. Each ECG parameter was examined for potential inclusion within multi-parameter A-ECG scores derived from multivariate regression models that were designed to optimally screen for disease in general or LVSD in particular. The performance of the best retrospectively-validated A-ECG scores was then compared against that of optimized pooled criteria from the strictly conventional ECG in a test set of 315 additional individuals. RESULTS: Compared to optimized pooled criteria from the strictly conventional ECG, a 7-parameter A-ECG score validated in the training set increased the sensitivity of resting ECG for identifying disease in the test set from 78% (72-84%) to 92% (88-96%) (P < 0.0001) while also increasing specificity from 85% (77-91%) to 94% (88-98%) (P < 0.05). In diseased patients, another 5-parameter A-ECG score increased the PPV of ECG for LVSD from 53% (41-65%) to 92% (78-98%) (P < 0.0001) without compromising related negative predictive value. CONCLUSION: Resting 12-lead A-ECG scoring is more accurate than strictly conventional ECG in screening for CAD, LVH and LVSD.

Diabetes does not affect ventricular repolarization and sudden cardiac death risk in patients with dilated cardiomyopathy.

BACKGROUND: We studied the effects of diabetes on ventricular repolarization parameters and sudden cardiac death in patients with dilated cardiomyopathy (DCM). METHODS: We enrolled 132 consecutive patients in New York Heart Association (NYHA) heart failure functional classes II or III and left ventricular ejection fraction <40% without evidence of coronary artery disease. In 45 patients (34%), diabetes was diagnosed according to standard criteria (study group), and the remaining 87 (66%) had no diabetes (controls). All patients underwent a 5-minute high-resolution electrocardiogram recording for determination of QT variability (QTV) index and were followed for 1 year thereafter. RESULTS: At baseline, the two groups did not differ in age, gender, left ventricular ejection fraction, NYHA functional class, or plasma brain natriuretic peptide levels. Similarly, QTV index did not differ between the study group (-0.51 +/- 0.55) and controls (-0.48 +/- 0.51; P = 0.48). During follow-up, 18 patients (14%) died of cardiac causes. Of the 18 deaths, eight were attributed to heart failure, and 10 to sudden cardiac death. Mortality was higher in the study group (10/45, 20%) than in controls (8/87, 10%) (P = 0.03). The same was true of the heart failure mortality (6/45 [13%] vs 2/87 [2%], P = 0.01), but not of the sudden cardiac death rate (3/45 [7%] vs 7/87 [8%], P = 0.78). By multiple variable analyses, diabetes predicted total and heart failure mortality, and a high QTV predicted sudden cardiac death. CONCLUSIONS: Diabetes appears to increase the risk of heart failure in patients with DCM without affecting ventricular repolarization parameters and sudden cardiac death risk.

The effect of Trendelenburg position, lactated Ringer's solution and 6% hydroxyethyl starch solution on cardiac output after spinal anesthesia.

BACKGROUND: The aim of our study was to evaluate the effects of Trendelenburg position, infusion of 6% hydroxyetyl starch solution or lactated Ringer's solution on changes in cardiac output (CO) after spinal anesthesia in patients older than 50 yr. METHODS: Seventy patients scheduled for lower extremity orthopedic surgery under spinal anesthesia were allocated randomly to one of the three treatment groups. In the Trendelenburg group, the patients were placed in the Trendelenburg position immediately after the spinal block for 10 min. In the hydroxyethyl starch group and the lactated Ringer's group, the patients received an infusion of 500 mL of 6% hydroxyethyl starch solution or 1000 mL of lactated Ringer's solution over 20 min after the spinal block. CO was measured continuously from 15 min before until 30 min after spinal anesthesia using the impedance cardiography method and arterial blood pressure with an automated device. P < 0.05 was considered statistically significant. RESULTS: The differences among treatment groups in CO were not statistically significant. Differences in the CO changes from baseline over time were significant. In the Trendelenburg group, CO did not change while the patient was in the Trendelenburg position. In the hydroxyethyl starch group, CO increased significantly after the block and remained significantly increased until the end of measurements. In the lactated Ringer's group, CO increased significantly 10 and 20 min after the block but, after stopping the infusion, CO started to decrease. CONCLUSIONS: Our study demonstrated that a decrease in CO after spinal anesthesia is prevented by placing the patient in the Trendelenburg position, or infusion of either lactated Ringer's solution or 6% hydroxyetyl starch solution. Although the effects of the infusion of the lactated Ringer's solution are transient, the effects of the infusion of 6% hydroxyethyl starch solution are extended beyond the time the infusion.

Atorvastatin therapy may reduce the incidence of sudden cardiac death in patients with advanced chronic heart failure.

BACKGROUND: In retrospective studies, statin therapy has been related to decreased incidence of sudden cardiac death (SCD) in heart failure. We sought to prospectively investigate a relation between atorvastatin therapy and SCD in patients with advanced chronic heart failure. METHODS AND RESULTS: We enrolled 110 patients with heart failure with a left ventricular ejection fraction less than 30% and cholesterol level greater than 150 mg/dL. Fifty-five patients were randomized to atorvastatin (10 mg/day) (statin group); the remaining 55 patients received no statins (controls). Patients were followed for 1 year. At baseline, the two groups did not differ in age, sex, left ventricular ejection fraction, cholesterol, B-type natriuretic peptide, heart rate variability, or QT variability. During follow-up, 29 patients died (26%) and 2 patients (2%) underwent heart transplantation. Of the 29 deaths, 13 were attributed to pump failure, 15 were attributed to SCD, and 1 was attributed to noncardiac causes. All-cause mortality was lower in the statin group (9/55, 16%) than in controls (20/55, 36%) (P = .017). The same was true of the SCD rate (3/55 [5%] vs. 12/55 [22%], P = .012), but not of the pump failure (5/55 [9%] vs. 8/55 [15%], P = .38). SCD-free survival was 2.3-times higher in the statin group than in controls (P = .01). CONCLUSIONS: Atorvastatin therapy seems to be associated with decreased incidence of SCD in patients with advanced chronic heart failure. Larger studies are ongoing to confirm this hypothesis.

Continuous axial contraction wave in the free wall of the guinea pig left ventricle.

We studied the variation from the simultaneous contraction of the normal left ventricle (LV). The pattern of the contraction along the LV long axes was assessed on the LV free wall on seven guinea pig hearts in situ with ultra fast video system and epicardial markers by means of the latitude and the size of the areas defined by markers. We found that the contraction occurs as a continuous contraction wave from the apex towards the base, which might yield functional adaptation of these two regions to diastolic and systolic function, respectively.

Real-time multichannel system for beat-to-beat QT interval variability.

The measurement of beat-to-beat QT interval variability (QTV) shows clinical promise for identifying several types of cardiac pathology. However, until now, there has been no device capable of displaying, in real time on a beat-to-beat basis, changes in QTV in all 12 conventional leads in a continuously monitored patient. Although several software programs have been designed to analyze QTV, heretofore, such programs have all involved only a few channels (at most) and/or have required laborious user interaction or offline calculations and postprocessing, limiting their clinical utility. This article describes a PC-based electrocardiogram software program recently codeveloped by our laboratories that, in real time, acquires, analyzes, and displays QTV in each of the 8 independent channels that constitute the 12-lead conventional electrocardiogram. The system also analyzes and displays the QTV from QT-interval signals that are derived from multiple channels and from singular value decomposition such that the effect of noise and other artifacts on the QTV results are substantially reduced compared with existing single-channel methods.

Atorvastatin therapy increases heart rate variability, decreases QT variability, and shortens QTc interval duration in patients with advanced chronic heart failure.

BACKGROUND: Although statins decrease the incidence of ventricular arrhythmias in patients with atherosclerotic heart disease, their potential antiarrhythmic effects in heart failure remain undefined. METHODS AND RESULTS: Of 80 heart failure patients enrolled, 40 were randomized to receive atorvastatin (statin group); the remaining 40 served as controls. At baseline and after 3 months, we measured heart rate variability (HRV), QT variability (QTV), and QTc interval using interactive high-resolution electrocardiogram analysis. The 2 groups did not differ in baseline HRV standard deviation of normal-to-normal intervals (SDNN) (RR): 24.6 +/- 2.8 ms in statin group versus 24.8 +/- 3.1 ms in controls, P = .72; square root of the mean of squared differences between successive intervals (rMSSD) (RR): 21.2 +/- 2.7 ms versus 21.7 +/- 2.9 ms, P = .43), QTV SDNN (QT): 6.4 +/- 1.5 ms versus 6.4+/-1.7, P = .96; rMSSD QT): 9.0 +/- 2.4 ms versus 8.7 +/- 2.9 ms, P = .65, and QTc interval 450 +/- 30 ms versus 446 +/- 27 ms, P = .59. At 3 months, the statin group displayed higher HRV SDNN RR): 27.2 +/- 4.9 ms versus 24.4 +/- 2.8 ms in controls, P = .003; rMSSD RR: 24.7 +/- 4.2 ms versus 21.3 +/- 5.6 ms, P = .004, lower QTV SDNN (QT): 5.1 +/- 1.9 ms versus 6.5 +/- 2.1, P = .004; rMSSD (QT): 6.6 +/- 2.8 ms versus 8.8 +/- 3.1 ms, P = .002, and shorter QTc interval 437 +/- 29 ms versus 450 +/- 25 ms, P = .03 than the control group. CONCLUSIONS: Atorvastatin increases HRV, decreases QTV, and shortens QTc interval, and may thereby reduce the risk of arrhythmias in patients with advanced heart failure.

Gender differences in knee kinematics and its possible consequences.

AIM: To analyze anatomic and kinematic characteristics of male and female knees in the sagittal plane. METHODS: Ten healthy male and 10 healthy female participants performed extension of their right lower leg in non-weight bearing and weight bearing conditions. The centers of knee joint motion were obtained by videographic motion analysis, and radii of condylar curves were calculated from digitalized X-ray scan. The Knee Roll software was made for this purpose. RESULTS: The extension of the knee in non-weight loaded and weight loaded conditions is a combination of rolling and sliding joint surface motion with 6:5 ratio, in both genders. During the last 20 degrees of the extension of weight loaded male knee, rolling/sliding ratio changed to 8:1 (P<0.05). Average radii of condylar curves were between 4.5 and 1.7 cm medially, and between 3.2 and 1.8 cm laterally, for 0 degrees and 90 degrees flexion contact point, respectively. Gender differences in the radii of condylar curves, after the adjusting to body height were insignificant. CONCLUSION: A higher proportion of joint surface sliding with consecutive anterior tibial displacement in women indicates more strain during knee extension, potentially making the female anterior cruciate ligament tend and susceptible to injury. The gender differences in the knee kinematics are probably the consequence of different soft tissue structure or its activity, because no difference in the sagittal shape of femoral condyles was noted.