Search

Aims Successful cardiac resynchronization therapy (CRT) shortens the pre-ejection period (PEP) which is prolonged in the left bundle branch block (LBBB). In a combined animal and patient study, we investigated if changes in the pulse arrival time (PAT) could be used to measure acute changes in PEP during CRT implantation and hence be used to evaluate acute CRT response non-invasively and in real time. Methods and results In six canines, a pulse transducer was attached to a lower limb and PAT was measured together with left ventricular (LV) pressure by micromanometer at baseline, after induction of LBBB and during biventricular pacing. Time-to-peak LV dP/dt (Td) was used as a surrogate for PEP. In twelve LBBB patients during implantation of CRT, LV and femoral pressures were measured at baseline and during five different pacing configurations. PAT increased from baseline (277 ± 9 ms) to LBBB (313 ± 16 ms, P < 0.05) and shortened with biventricular pacing (290 ± 16 ms, P < 0.05) in animals. There was a strong relationship between changes in PAT and Td in patients (r2 = 0.91). Two patients were classified as non-responders at 6 months follow-up. CRT decreased PAT from 320 ± 41 to 298 ± 39 ms (P < 0.05) in the responders, while PAT increased by 5 and 8 ms in the two non-responders. Conclusion This proof-of-concept study indicates that PAT can be used as a simple, non-invasive method to assess the acute effects of CRT in real time with the potential to identify long-term response in patients.

Cardiac resynchronization therapy (CRT) is an effective treatment for a subgroup of heart failure (HF) patients, but more than 30% of those selected do not improve after CRT implantation. Imperfect pre-procedural criteria for patient selection and optimization are the main causes of the high non-response rate. In this study, we evaluated a novel measure for assessing CRT response. We used a computational modeling framework to calculate the regional stress of the left ventricular wall of seven CRT patients and seven healthy controls. The standard deviation of regional wall stress at the time of mitral valve closure (SD_MVC) was used to quantify dyssynchrony and compared between patients and controls and among the patients. The results show that SD_MVC is significantly lower in controls than patients and correlates with long-term response in patients, based on end-diastolic volume reduction. In contrast to our initial hypothesis, patients with lower SD_MVC respond better to therapy. The patient with the highest SD_MVC was the only non-responder in the patient cohort. The distribution of fiber stress at the beginning of the isovolumetric phase seems to correlate with the degree of response and the use of this measurement could potentially improve selection criteria for CRT implantation. Further studies with a larger cohort of patients are needed to validate these results.

Aims Three distinct septal contraction patterns typical for left bundle branch block may be assessed using echocardiography in heart failure patients scheduled for cardiac resynchronization therapy (CRT). The aim of this study was to explore the association between these septal contraction patterns and the acute haemodynamic and electrical response to biventricular pacing (BIVP) in patients undergoing CRT implantation. Methods and results Thirty-eight CRT candidates underwent speckle tracking echocardiography prior to device implantation. The patients were divided into two groups based on whether their septal contraction pattern was indicative of dyssynchrony (premature septal contraction followed by various amount of stretch) or not (normally timed septal contraction with minimal stretch). CRT implantation was performed under invasive left ventricular (LV) pressure monitoring and we defined acute CRT response as ≥10% increase in LV dP/dtmax. End-diastolic pressure (EDP) and QRS width served as a diastolic and electrical parameter, respectively. LV dP/dtmax improved under BIVP (737 ± 177 mmHg/s vs. 838 ± 199 mmHg/s, P Conclusion Septal contraction patterns are an excellent predictor of acute CRT response. Only patients with premature septal contraction experienced acute systolic, diastolic, and electrical improvement under BIVP.

Objectives This study sought to investigate how regional left ventricular (LV) function modifies septal motion in left bundle branch block (LBBB). Background In LBBB, the interventricular septum often has marked pre-ejection shortening, followed by immediate relengthening (rebound stretch). This motion, often referred to as septal flash, is associated with positive response to cardiac resynchronization therapy (CRT). Methods In 10 anesthetized dogs, we induced LBBB by radiofrequency ablation and occluded the circumflex (CX) (n = 10) and left anterior descending (LAD) (n = 6) coronary arteries, respectively. Myocardial dimensions were measured by sonomicrometry and myocardial work by pressure-segment length analysis. In 40 heart failure patients with LBBB, including 20 with post-infarct scar and 20 with nonischemic cardiomyopathy, myocardial strain was measured by speckle-tracking echocardiography and myocardial work by pressure-strain analysis. Scar was assessed by cardiac magnetic resonance imaging with late gadolinium enhancement. Results During LBBB, each animal showed typical septal flash with pre-ejection shortening and rebound stretch, followed by reduced septal systolic shortening (p Conclusions LV lateral wall dysfunction and scar abolished septal flash and markedly improved septal function in LBBB. Therefore, function and scar in the LV lateral wall should be taken into account when septal motion is used to evaluate dyssynchrony.

Cardiac disease is a leading cause of death worldwide. Disturbance in the conduction system of the heart may trigger or aggravate heart dysfunction, affecting the efficiency of the heart, and lead to heart failure or cardiac arrest. Patients may require implantable cardiac rhythm management devices (ICRMDs) to maintain or restore the heart rhythm. ICRMDs have undergone important improvements, yet limitations still exist, presenting important technological challenges. Most ICRMDs consist of a subcutaneous control unit and intracardiac electrodes. The leads, which connect the electrodes to the control unit, are usually placed transvenously through the subclavian veins. Various locations inside the heart are used for placement of electrodes, depending on the specific condition. Some of the limitations to effective pacemaker therapy are associated with placement and location of the leads. Various approaches have been developed to overcome these challenges, such as multi-site pacing and leadless solutions. This paper aims to review the state of the art for the selection of placement sites for pacemakers, implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy devices (CRT) devices and discuss potential technological advancements to improve the results of ICRMD-therapy including development av leadless technology.

Cardiac resynchronization therapy (CRT) can substantially improve dyssynchronous heart failure and reduce mortality. However, about one-third of patients who are implanted, derive no measurable benefit from CRT. Non-response may partly be due to suboptimal activation of the left ventricle (LV) caused by electrophysiological heterogeneities. The goal of this study is to investigate the performance of a newly developed method used to analyze electrical wavefront propagation in a heart model including myocardial scar and compare this to clinical benchmark studies. We used computational models to measure the maximum activation front (MAF) in the LV during different pacing scenarios. Different heart geometries and scars were created based on cardiac MR images of three patients. The right ventricle (RV) was paced from the apex and the LV was paced from 12 different sites, single site, dual-site and triple site. Our results showed that for single LV site pacing, the pacing site with the largest MAF corresponded with the latest activated regions of the LV demonstrated during RV pacing, which also agrees with previous markers used for predicting optimal single-site pacing location. We then demonstrated the utility of MAF in predicting optimal electrode placements in more complex scenarios including scar and multi-site LV pacing. This study demonstrates the potential value of computational simulations in understanding and planning CRT.

Aims A difficult cardiac resynchronization therapy (CRT) implantation scenario emerges when no lateral pacing option exists. The aim of this study was to explore the effect of biventricular pacing (BIVP) on vectorcardiographic parameters in patients with a non-lateral left ventricular (LV) lead position. We hypothesized that perimeter and area reduction for both the QRS complex and T-wave would predict acute CRT response. Methods and results Twenty-six patients (14 ischaemic) with a mean age of 63 ± 10 years and standard CRT indication underwent device implantation with continuous LV pressure registration. The LV lead was placed in either an anterior or apical position. Biventricular pacing was performed at a rate 10% above intrinsic rhythm with acute CRT response defined as LV ΔdP/dtmax >10%. Using this criterion 12 patients were identified as acute CRT responders (responders: 16.7 ± 4.8% vs. non-responders: 1.9 ± 5.3%, P

Cardiac resynchronization therapy (CRT) is a frequently effective treatment modality for dyssynchronous heart failure, however, 30% of patients do not respond, usually due to suboptimal activation of the left ventricle (LV). Multisite pacing (MSP) may increase the response rate, but its effect in the presence of myocardial scars is not fully understood. We use a computational model to study the outcome of MSP in an LV with scars in two different locations and of two different sizes. The LV was stimulated from anterior, posterior and lateral locations individually and in pairs, while a septal stimulation site represented right ventricular (RV) pacing. Intraventricular pressures were measured, and outcomes evaluated in terms of maximum LV pressure gradient (dP/dtmax)- change compared to isolated RV pacing. The best result obtained using various LV pacing locations included a combination of sites remote from scars and the septum. The highest dP/dtmax increase was achieved, regardless of scar size, using MSP with one pacing site located on the LV free wall opposite to the scar and one site opposite to the septum. These in silico modelling results suggest that making placement of pacing electrodes dependent on location of scarring, may alter acute haemodynamics and that such modelling may contribute to future CRT optimization.

We investigated whether tachycardia in left bundle branch block (LBBB) decreases left ventricular (LV) diastolic distensibility and increases diastolic pressures due to incomplete relaxation, and if cardiac resynchronization therapy (CRT) modifies this response. Thirteen canines were studied at baseline heart rate (120 beats/min) and atrial paced tachycardia (180 beats/min) before and after induction of LBBB and during CRT. LV and left atrial pressures (LAP) were measured by micromanometers and dimensions by sonomicrometry. The time constant τ of exponential pressure decay and degree of incomplete relaxation at mitral valve opening (MVO) and end diastole (ED) based on extrapolation of the exponential decay were assessed. Changes in LV diastolic distensibility were investigated using the LV transmural pressure-volume (PV) relation. LBBB caused prolongation of τ ( P < 0.03) and increased the degree of incomplete relaxation during tachycardia at MVO ( P < 0.001) and ED ( P = 0.08) compared with normal electrical activation. This was associated with decreased diastolic distensibility seen as upward shift of the PV relation at MVO by 18.4 ± 7.0 versus 12.0 ± 5.0 mmHg, at ED by 9.8 ± 2.3 versus 4.7 ± 2.3 mmHg, and increased mean LAP to 11.4 ± 2.7 versus 8.5 ± 2.6 mmHg, all P < 0.006. CRT shifted the LV diastolic PV relation downwards during tachycardia, reducing LAP and LV diastolic pressures ( P < 0.03). Tachycardia in LBBB reduced LV diastolic distensibility and increased LV diastolic pressures due to incomplete relaxation, whereas CRT normalized these effects. Clinical studies are needed to determine whether a similar mechanism contributes to dyspnea and exercise intolerance in LBBB and if effects of CRT are heart rate dependent. NEW & NOTEWORTHY Compared with normal electrical conduction, tachycardia in left bundle branch block resulted in incomplete relaxation during filling, particularly of the late activated left ventricular lateral wall. This further resulted in reduced left ventricular diastolic distensibility and elevated diastolic pressures and thus amplified the benefits of cardiac resynchronization therapy in this setting.

Goal: Hexahedral automatic model generation is a recurrent problem in computer vision and computational biomechanics. It may even become a challenging problem when one wants to develop a patient-specific finite element (FE) model of the left ventricle (LV), particularly when only low resolution images are available. In the present study, a fast and efficient algorithm is presented and tested to address such a situation. Methods: A template FE hexahedral model was created for an LV geometry using a general electric ultrasound (US) system. A system of centerline was considered for this LV mesh. Then, the nodes located over the endocardial and epicardial surfaces are, respectively, projected from this centerline onto the actual endocardial and epicardial surfaces reconstructed from a patient's US data. Finally, the position of the internal nodes is derived by finding the deformations with minimal elastic energy. This approach was applied to eight patients suffering from congestive heart disease. An FE analysis was performed to derive the stress induced in the LV tissue by diastolic blood pressure on each of them. Results: Our model morphing algorithm was applied successfully and the obtained meshes showed only marginal mismatches when compared to the corresponding US geometries. The diastolic FE analyses were successfully performed in seven patients to derive the distribution of principal stresses. Conclusion: The original model morphing algorithm is fast and robust with low computational cost. Significance: This low-cost model morphing algorithm may be highly beneficial for future patient-specific reduced-order modeling of the LV with potential application to other crucial organs.

Response to cardiac resynchronization therapy (CRT) may be improved if coronary venous anatomy is fused with information on regional left ventricular (LV) function to guide LV lead placement. We propose a method to register a 3D model of the LV and its corresponding coronary venous tree (reconstructed from biplane X-ray fluoroscopy) for CRT applications. A template coronary venous tree (CVT) centerline, learned from a training set, was utilized to find point-to-point correspondence between the LV surface and the coronary vessels. The method was validated retrospectively on a set of 15 CRT candidates. Two validation experiments were conducted; on a randomly relocated patient specific LV and on a randomly relocated average LV. The absolute distance error between the ground truth and the registered LV was 3.4±1.0 mm for the case of patient specific LV and 4.2±1.0 mm for the case of average LV model. The probability of targeting the correct coronary branch, when using the registered LV compared to the ground truth, was 95.3±2.5 % for the case of patient specific LV and 94.5±3.5 % for the case of average LV model. The results suggest that the method can be used to provide an automatic registration of a 3D LV model to X-ray imaging with potential applications in image fusion to aid image-guided CRT implantation.

Background Drug therapy for ADHD (Attention Deficit Hyperactivity Disorder) has generally been regarded as safe. ECG screening of healthy children and adolescents before initiating this type of treatment appears to be usual in Norway, despite recommendations that ECGs should only be undertaken in individuals who are at risk. The purpose of this article is to clarify relevant guidelines for cardiovascular risk assessment for the use of ADHD drugs in children and adolescents, as well as to propose practical recommendations. Method The article is based on a literature search in PubMed completed on 1 October 2013, and on the author's own clinical experience and discretionary assessments. Results The use of CNS stimulants and atomoxetine is associated with a slight rise in blood pressure and pulse rate, as well as small changes in QT interval. A small percentage of patients (5-10%) experience a clinically significant rise in blood pressure and pulse rate. Sudden death does not appear to occur more frequently in children and adolescents taking ADHD drugs in therapeutic doses than in children and adolescents who do not use such drugs. There is little knowledge available on the long-term effects of ADHD drugs on the cardiovascular system of otherwise healthy individuals, or on the risk related to the use of ADHD drugs in children and adolescents with cardiac disease. The drugs are thought to increase the risk of sudden cardiac death in some arrhythmia syndromes. Interpretation Our assessment is that caution should be exercised in the use of ADHD drugs in children with potentially dangerous cardiac arrhythmias. We recommend clinical examination and a thorough medical history review in order to identify individuals at risk before initiating drug therapy, and also suggest that it is not necessary for healthy children to be given an ECG examination before introducing ADHD drugs. In children with known cardiac disease, arrhythmia or risk factors for cardiac disease, ADHD treatment should be undertaken in consultation with a medical specialist with competence in pediatric cardiology.

Computational models of cardiac mechanics, personalized to a patient, offer access to mechanical information above and beyond direct medical imaging. Additionally, such models can be used to optimize and plan therapies in-silico, thereby reducing risks and improving patient outcome. Model personalization has traditionally been achieved by data assimilation, which is the tuning or optimization of model parameters to match patient observations. Current data assimilation procedures for cardiac mechanics are limited in their ability to efficiently handle high-dimensional parameters. This restricts parameter spatial resolution, and thereby the ability of a personalized model to account for heterogeneities that are often present in a diseased or injured heart. In this paper, we address this limitation by proposing an adjoint gradient-based data assimilation method that can efficiently handle high-dimensional parameters. We test this procedure on a synthetic data set and provide a clinical example with a dyssynchronous left ventricle with highly irregular motion. Our results show that the method efficiently handles a high-dimensional optimization parameter and produces an excellent agreement for personalized models to both synthetic and clinical data.

Acceleration has been measured both noninvasively and invasively, during both isovolumic contraction and early ejection and has been shown to reflect contractility, especially through correlation with dP/dt(max) . In this study timing and amplitude of mitral valve annulus acceleration assessed by tissue Doppler were measured and related to diastolic and systolic events. Invasive load independent measures of contractility, based on pressure-volume relationships, were derived, and pacing was done to modulate and control heart rate. Peak systolic acceleration (pSac) of the mitral valve annulus was shown to occur slightly later but timely related to dP/dt(max) (P < 0.05), while peak preejection acceleration (pPac) was related to diastolic events. During inotropy and preload modulation dP/dt(max) was found to be the strongest determinant of pSac (β= 0.9 ± 0.1; P < 0.001 and β= 1.3 ± 0.4; P < 0.001, respectively, log-transformed variables). PSac increased with pacing at a higher rate (β= 0.1 ± 0.0 cm/sec(2), P = 0.03). Furthermore, pSac indexed to end-diastolic volume (EDV) was linearly correlated to load independent contractility parameters (E(max), R = 0.7; ESPVR, R = 0.7; and PRSW, R = 0.5), and proved stable toward changes in preload and afterload. The relation between dP/dt(max)/EDV and pSac/EDV was stable throughout the study. In conclusion we found that peak systolic longitudinal acceleration (pSac) of the mitral valve annulus during aortic valve opening is strongly associated with dP/dt(max). Indexed to EDV, pSac may represent a load independent noninvasive contractility parameter. We consider pSac a candidate marker of long-axis contractility which should be viewed upon as the long-axis contribution to dP/dt(max).

Systolic longitudinal myocardial function is important for cardiac ejection. Data describing hemodynamic determinants and the time course of myocardial longitudinal contraction as measured by tissue Doppler are lacking. Ten newborn pigs were used for invasive hemodynamic investigation. Tissue Doppler assessment of the lateral part of the mitral valve annulus during systole was performed during pharmacological modulation of inotropy, cardiac pacing, and modulations of loading conditions. The strongest association was found between peak systolic velocity (S') and peak systolic flow (PSF) and end-systolic pressure (ESP), respectively (β = 0.09 cm/mL, p < 0.001 and β = -0.07 cm/mL, p = 0.003). Displacement (D) was mostly influenced by stroke volume (SV) (β = 0.05 cm/mL, p < 0.001). Ejection time, SV, ESP, maximum first derivative of pressure (dP/dtmax), and PSF were all associated with S' and D under different states of hemodynamic modulation; however, the ratio between PSF and S', SV, and D were stable during hemodynamic modulations. Normalized cross correlations indicate that S' and D follow the same trajectory as flow and SV, respectively. In conclusion, this study provides validity of accounting systolic D in the long axis as the longitudinal contribution to SV and peak systolic tissue velocity as the longitudinal contribution to PSF.

BackgroundPatient-specific left ventricular (LV) lead optimisation strategies with immediate feedback on cardiac resynchronisation therapy (CRT) effectiveness are needed. The purpose of this study was to compare contractility surrogates derived from biventricular lead motion analysis to the peak positive time derivative of LV pressure (dP/dtmax) in patients undergoing CRT implantation.MethodsTwenty-seven patients underwent CRT implantation with continuous haemodynamic monitoring. The right ventricular (RV) lead was placed in apex and a quadripolar LV lead was placed laterally. Biplane fluoroscopy cine films facilitated construction of three-dimensional RV–LV interlead distance waveforms at baseline and under biventricular pacing (BIVP) from which the following contractility surrogates were derived; fractional shortening (FS), time to peak systolic contraction and peak shortening of the interlead distance (negative slope). Acute haemodynamic CRT response was defined as LV ∆dP/dtmax ≥ 10 %.ResultsWe observed a mean increase in dP/dtmax under BIVP (899±205 mm Hg/s vs 777±180 mm Hg/s, pmax, 18 patients were classified as acute CRT responders and nine as non-responders (23.3%±10.6% vs 1.9±5.3%, pConclusionThe baseline RV–LV interlead distance was associated with echocardiographic LV dimensions. In CRT recipients, contractility surrogates derived from the RV–LV interlead distance waveform could not discriminate between acute haemodynamic responders and non-responders.

This study aimed to assess the effect of correcting for the impact of heart rate (HR) or ejection time (ET) on myocardial velocities in the long axis in piglets undergoing hypoxia. The ability to eject a higher volume at a fixed ET is a characteristic of contractility in the heart. Systolic velocity of the atrioventricular annulus displacement is directly related to volume changes of the ventricle. Both ET and systolic velocity may be measured in a single heartbeat. In 29 neonatal pigs, systolic velocity and ET were measured with tissue Doppler techniques in the mitral valve annulus, the tricuspid valve annulus, and the septum. All ejection time corrected velocities (S((ET)), mean ± SEM, cm/s) decreased significantly during hypoxia (S(mva(ET)) 15.5 ± 0.2 to 13.2 ± 0.3 (p0.001), S(septal(ET)) 9.9 ± 0.1 to 7.8 ± 0.2 (p0.001), S(tva(ET)) 12.1 ± 0.2 to 9.8 ± 0.3 (p0.001)). The magnitude of change from baseline to hypoxia was greater for ejection time corrected systolic velocities than for RR-interval corrected velocities (mean ± SEM, cm/s); ΔS(mva(ET)) 2.3 ± 2.0 vs. ΔS(mva(RR)) 1.6 ± 1.1 (p = 0.02), ΔS(septal(ET)) 2.1 ± 1.0 vs. ΔS(septal(RR)) 1.6 ± 1.0 (p0.01), ΔS(tva(ET)) 2.3 ± 1.1 vs. ΔS(tva(RR)) 1.8 ± 1.3 (p = 0.04). The receiver operator characteristic (ROC) showed superior performance of S((ET)) compared with uncorrected velocities. The decrease in S((ET)) during hypoxia was not influenced by important hemodynamic determinants. ET-corrected systolic velocity improves accuracy and decreases variability in the evaluation of systolic longitudinal function and contractility during global hypoxia in neonatal pigs compared with systolic velocity alone. It is robust toward hemodynamic changes. This novel method has the potential of becoming a useful tool in clinical practice.

Cardiac resynchronization therapy (CRT) reduces mortality and hospitalization in heart failure patients with left bundle branch block. Studies have shown that left ventricular (LV) lead placement is important to the acute response to CRT. The aim of this study was to evaluate if LV lead placement

The most common reason for heart failure in children is volume overload secondary to a left-to-right shunt. Therefore, an accurate diagnosis with identification of possible surgical or interventional reactions should be the first priority. Medical therapy is mainly based on diuretics, angiotensin-converting enzyme inhibitors, cardiac glycosides and beta-blockers. There are few prospective trials in pediatric cardiology, but the available data reach a similar conclusion to that of adults with heart failure. Diuretics are an important tool in patients with fluid retention, and angiotensin-converting enzyme inhibitors are helpful in patients with volume overload of the ventricles. Cardiac glycosides are still in use, but there is a trend toward primary use of diuretics. Angiotensin-converting enzyme inhibitors and beta-blockers have been used successfully in the treatment of heart failure in children, but there are limited data on its efficacy.

Summary Computational models of cardiac mechanics, personalized to a patient, offer access to mechanical information above and beyond direct medical imaging. Additionally, such models can be used to optimize and plan therapies in-silico, thereby reducing risks and improving patient outcome. Model personalization has traditionally been achieved by data assimilation, which is the tuning or optimization of model parameters to match patient observations. Current data assimilation procedures for cardiac mechanics are limited in their ability to efficiently handle high dimensional parameters. This restricts parameter spatial resolution, and thereby the ability of a personalized model to account for heterogeneities that are often present in a diseased or injured heart. In this paper we address this limitation by proposing an adjoint-gradient based data assimilation method that can efficiently handle high-dimensional parameters. We test this procedure on a synthetic data set, and provide a clinical example with a dyssynchronous left ventricle with highly irregular motion. Our results show that the method efficiently handles a high dimensional optimization parameter, and produces an excellent agreement for personalized models to both synthetic and clinical data. This article is protected by copyright. All rights reserved.

Drug therapy for ADHD (Attention Deficit Hyperactivity Disorder) has generally been regarded as safe. ECG screening of healthy children and adolescents before initiating this type of treatment appears to be usual in Norway, despite recommendations that ECGs should only be undertaken in individuals who are at risk. The purpose of this article is to clarify relevant guidelines for cardiovascular risk assessment for the use of ADHD drugs in children and adolescents, as well as to propose practical recommendations.The article is based on a literature search in PubMed completed on 1 October 2013, and on the author's own clinical experience and discretionary assessments.The use of CNS stimulants and atomoxetine is associated with a slight rise in blood pressure and pulse rate, as well as small changes in QT interval. A small percentage of patients (5-10%) experience a clinically significant rise in blood pressure and pulse rate. Sudden death does not appear to occur more frequently in children and adolescents taking ADHD drugs in therapeutic doses than in children and adolescents who do not use such drugs. There is little knowledge available on the long-term effects of ADHD drugs on the cardiovascular system of otherwise healthy individuals, or on the risk related to the use of ADHD drugs in children and adolescents with cardiac disease. The drugs are thought to increase the risk of sudden cardiac death in some arrhythmia syndromes.Our assessment is that caution should be exercised in the use of ADHD drugs in children with potentially dangerous cardiac arrhythmias. We recommend clinical examination and a thorough medical history review in order to identify individuals at risk before initiating drug therapy, and also suggest that it is not necessary for healthy children to be given an ECG examination before introducing ADHD drugs. In children with known cardiac disease, arrhythmia or risk factors for cardiac disease, ADHD treatment should be undertaken in consultation with a medical specialist with competence in pediatric cardiology.

Electrical bioimpedance has been used over the years to measure various physiological parameters. Due to lack of high-speed instruments, there have been few options for making multi-frequency measurement series with high temporal resolution. This situation has changed lately, and with access to a commercially available impedance spectrometer, we have used this as part of an enhanced measurement set-up capable of measuring both bioimpedance and biopotentials with a temporal resolution in the millisecond-range. The set-up is controlled by a computer which also displays and processes the measurement data. Results from measurements in a human heart are shown. In these measurements, we can clearly see differences in the signal trajectory at current frequencies. The different trajectories indicate that with change in frequencies different physiological properties are reflected. We have shown that it is possible to detect changes in waveform morphology caused by a change in pacing modality. The ECG and EGM give additional information on global heart activity and electrical activity surrounding the electrodes. This measurement set-up allows us to further investigate bio-impedance as a measurement tool for rapid changes in impedance, such as in the cardiac field. The study was approved by the local institutional review boards (2014/1223/REK sor-ost A).

Patients with congenital heart disease and univentricular circulation are vulnerable to ventricular dysfunction. In the context of atrioventricular conduction defects, a ventricular pacemaker may be placed, possibly introducing dyssynchronous wall motion and deterioration of ventricular pump function. We describe such a case in which repositioning of the ventricular lead restored synchronicity.

Nuclear factor kappa B (NF-κB) is considered an important mediator of inflammation, but is also important for developing organs and is constitutive active in neurons in the newborn brain.We wanted to test the effects of preconditioning with nicotine on neonatal mice subjected to hypoxia and reoxygenated with either room-air or 100% oxygen. We hypothesized that nicotine would be neuroprotective and possibly reduce detrimental effects of 100% oxygen on body organs.In this randomized study, we used neonatal transgenic NF-κB reporter mice that were preconditioned with nicotine or vector only prior to hypoxia, and then subjected to resuscitation with room-air or 100% oxygen.We did not find any differences in NF-κB activity in whole body or in the brain of animals resuscitated with room-air or 100% oxygen. Resuscitation with 100% oxygen attenuated NF-kB activity when compared with resuscitation with room-air. However, when bioluminescence was properly corrected for body weight, the difference between room-air and 100% reoxygenation was no longer evident.Preconditioning with nicotine does not have any effect on NF-κB activity in body organs or in the brain of neonatal mice after hypoxia and resuscitation with either room-air or 100% oxygen. 100% oxygen did not alter NF-κB activity when compared to room-air resuscitation alone.

Acceleration has been measured both noninvasively and invasively, during both isovolumic contraction and early ejection and has been shown to reflect contractility, especially through correlation with dP/dt(max) . In this study timing and amplitude of mitral valve annulus acceleration assessed by tissue Doppler were measured and related to diastolic and systolic events. Invasive load independent measures of contractility, based on pressure-volume relationships, were derived, and pacing was done to modulate and control heart rate. Peak systolic acceleration (pSac) of the mitral valve annulus was shown to occur slightly later but timely related to dP/dt(max) (P0.05), while peak preejection acceleration (pPac) was related to diastolic events. During inotropy and preload modulation dP/dt(max) was found to be the strongest determinant of pSac (β= 0.9 ± 0.1; P0.001 and β= 1.3 ± 0.4; P0.001, respectively, log-transformed variables). PSac increased with pacing at a higher rate (β= 0.1 ± 0.0 cm/sec(2), P = 0.03). Furthermore, pSac indexed to end-diastolic volume (EDV) was linearly correlated to load independent contractility parameters (E(max), R = 0.7; ESPVR, R = 0.7; and PRSW, R = 0.5), and proved stable toward changes in preload and afterload. The relation between dP/dt(max)/EDV and pSac/EDV was stable throughout the study. In conclusion we found that peak systolic longitudinal acceleration (pSac) of the mitral valve annulus during aortic valve opening is strongly associated with dP/dt(max). Indexed to EDV, pSac may represent a load independent noninvasive contractility parameter. We consider pSac a candidate marker of long-axis contractility which should be viewed upon as the long-axis contribution to dP/dt(max).

Background: Resuscitation with 100% oxygen increases oxidative stress and is detrimental for organ function. Objective: To study the effects of resuscitation with 100% oxygen compared to room-air on myocardial function. Methods: Twenty-eight newborn pigs underwent global hypoxia (8% oxygen/N2) until base excess reached –20 mmol/l. The animals were randomized into two groups and resuscitated with either 100% or room air for 30 min. Myocardial tissue Doppler velocities and acceleration of the mitral and tricuspid valve annuli during systole and diastole were assessed before global hypoxia and after resuscitation together with troponin I. Results: Peak early diastolic velocity (E′) and acceleration (pEac) in the septum and pEac in the lateral tricuspid valve annulus were lower after resuscitation with 100% oxygen, suggesting impaired diastolic relaxation in the right ventricle. Lower systolic velocities and acceleration in the right ventricle relative to heart rate indicate disruption of the right ventricular force-frequency relationship after resuscitation with 100% oxygen. Troponins were higher in the 100% oxygen group, suggesting increased myocardial damage in this group. Conclusion: Resuscitation with 100% oxygen compared to room air induces diastolic dysfunction, disrupts the systolic force-frequency relationship and increases myocardial damage in the newborn pig.

Background: Global hypoxia may affect regions of the neonatal heart during systole and diastole differently. Objective: In the first study, the aim was to assess longitudinal myocardial function in newborn pigs during global hypoxia and recovery. In the second study, invasive hemodynamic data were evaluated and compared with tissue velocities and acceleration. Methods: Myocardial Doppler measurements of velocity and acceleration in the atrioventricular valve annuli during global hypoxia were made. Results: In the first experiment, systolic velocity (S), early diastolic velocity (E’) and peak systolic acceleration (pSac) decreased during hypoxia. S, pSac and E’mva (mitral valve annulus) recovered after reoxygenation, while E’septal and E’tva (tricuspid valve annulus) did not. Isovolumic acceleration (IVA) did not reflect systolic dysfunction. In the second experiment, Smva and pSacmva declined during hypoxia similarly to maximum dP/dT. E’mva and E’tva were correlated with τ and both changed parallel to minimum dP/dT. In the TVA maximum dP/dT and pSactva did not change, while Stva declined. By correcting for heart rate the pattern of alteration in S and pSac became comparable to the changes in E’. Conclusion: Tissue Doppler velocity in systole, diastole and acceleration during rapid ejection reflect hemodynamic changes in the neonatal myocardium during global hypoxia and recovery. S and pSac reflect systolic function, while E’ correlates with τ and mirrors diastolic function.

Introduction: Oxidative stress in the newborn period may cause cell injury and inflammation if the antioxidant capacity is insufficient. To monitor antioxidant and inflammatory activity we examined by in vivo imaging various strains of luciferase reporter mice whose light-emitting properties were regulated by response elements or complete promoters related to oxidative stress and/or inflammation. The aim of this study is to present a model that can monitor genetic activity in vivo during pregnancy and the first 10 days of life. Methods: One mouse strain reports the activity of nuclear factor-ĸB (NF-ĸB) activity, a transcription factor essential for modulating inflammation, apoptosis, differentiation and cell growth. A second mouse strain reports on superoxide dismutase 1-promoter activity. A third strain reports the promoter activity of γ-glutamylcysteine synthetase, the rate limiting enzyme in glutathione production, and the last strain reports on antioxidant responsive element (ARE)/electrophil responsive element. Wild-type female mice mated with NF-ĸB mice were imaged through pregnancy to monitor intrauterine NF-ĸB activation. Results: Intrauterine NF-ĸB activity increased dramatically from day 17 towards labor. During the first 4 days of life luminescence measured was intense in all mice with distinct strain differences. All strains had high luminescence levels at day 1 and a considerably lower level at day 10. Conclusion: This model allows investigation of the transcriptional regulation of key proteins related to oxidative stress and inflammation in pregnancy and the first days of life. With very little stress to the newborn animals genetic activity can be monitored day by day.

Recent studies show that the response rate to cardiac resynchronization therapy (CRT) could be improved if the left ventricle (LV) is paced at the site of the latest mechanical activation, but away from the myocardial scar. A prototype system for CRT lead placement guidance that combines LV functional information from ultrasound with live x-ray fluoroscopy was developed. Two mean anatomical models, each containing LV epi-, LV endo- and right ventricle endocardial surfaces, were computed from a database of 33 heart failure patients as a substitute for a patient-specific model. The sphericity index was used to divide the observed population into two groups. The distance between the mean and the patient-specific models was determined using a signed distance field metric (reported in mm). The average error values for LV epicardium were [Formula: see text] and for LV endocardium were [Formula: see text]. The validity of using average LV models for a CRT procedure was tested by simulating coronary vein selection in a group of 15 CRT candidates. The probability of selecting the same coronary branch, when basing the selection on the average model compared to a patient-specific model, was estimated to be [Formula: see text]. This was found to be clinically acceptable.