Displaying publications 1 - 20 of 26 in total

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  1. Fluid structure interaction simulation of left ventricular flow dynamics under left ventricular assist device support
    Ong CW, Chan BT, Lim E, Abu Osman NA, Abed AA, Dokos S, et al.
    Annu Int Conf IEEE Eng Med Biol Soc, 2012;2012:6293-6.
    PMID: 23367368 DOI: 10.1109/EMBC.2012.6347433
    For patient's receiving mechanical circulatory support, malfunction of the left ventricular assist device (LVADs) as well as mal-positioning of the cannula imposes serious threats to their life. It is therefore important to characterize the flow pattern and pressure distribution within the ventricle in the presence of an LVAD. In this paper, we present a 2D axisymmetric fluid structure interaction model of the passive left ventricle (LV) incorporating an LVAD cannula to simulate the effect of the LVAD cannula placement on the vortex dynamics. Results showed that larger recirculation area was formed at the cannula tip with increasing cannula insertion depth, and this is believed to reduce the risk of thrombus formation. Furthermore, we also simulated suction events (collapse of the LV) by closing the inlet. Vortex patterns were significantly altered under this condition, and the greatest LV wall displacement was observed at the part of the myocardium closest to the cannula tip.
    Matched MeSH terms: Heart Ventricles/physiopathology*
  2. Simulation of left ventricle flow dynamics with dilated cardiomyopathy during the filling phase
    Chan BT, Ong CW, Lim E, Abu Osman NA, Al Abed A, Lovell NH, et al.
    Annu Int Conf IEEE Eng Med Biol Soc, 2012;2012:6289-92.
    PMID: 23367367 DOI: 10.1109/EMBC.2012.6347432
    Dilated cardiomyopathy (DCM) is a common cardiac disease which leads to the deterioration in cardiac performance. A computational fluid dynamics (CFD) approach can be used to enhance our understanding of the disease, by providing us with a detailed map of the intraventricular flow and pressure distributions. In the present work, effect of ventricular size on the intraventricular flow dynamics and intraventricular pressure gradients (IVPGs) was studied using two different implementation methods, i.e. the geometry-prescribed and the fluid structure interaction (FSI) methods. Results showed that vortex strength and IVPGs are significantly reduced in a dilated heart, leading to an increased risk of thrombus formation and impaired ventricular filling. We suggest FSI method as the ultimate method in studying ventricular dysfunction as it provides additional cardiac disease prognostic factors and more realistic model implementation.
    Matched MeSH terms: Heart Ventricles/physiopathology*
  3. Evaluation of suction detection during different pumping states in an implantable rotary blood pump
    Ng SC, Lim E, Mason DG, Avolio AP, Lovell NH
    Artif Organs, 2013 Aug;37(8):E145-54.
    PMID: 23635073 DOI: 10.1111/aor.12079
    In recent times, the problem of noninvasive suction detection for implantable rotary blood pumps has attracted substantial research interest. Here, we compare the performance of various suction indices for different types of suction and non-suction events based on pump speed irregularity. A total of 171 different indices that consist of previously proposed as well as newly introduced suction indices are tested using regularized logistic regression. These indices can be classified as amplitude based (derived from the mean, maximum, and minimum values of a cycle), duration based (derived from the duration of a cycle), gradient based (derived from the first order as well as higher order differences) and frequency based (derived from the power spectral density). The non-suction event data consists of ventricular ejection with or without arrhythmia and intermittent and continuous non-opening of the aortic valve. The suction event data consists of partial ventricular collapse that occurs intermittently as well as continuously with or without arrhythmia. In addition, we also attempted to minimize the usage of multiple indices by applying the sequential forward floating selection method to find which combination of indices gives the best performance. In general, the amplitude-based and gradient-based indices performed quite well while the duration-based and frequency-based indices performed poorly. By having only two indices ([i] the maximum gradient change in positive slope; and [ii] the standard deviation of the maximum value in a cycle), we were able to achieve a sensitivity of 98.9% and a specificity of 99.7%.
    Matched MeSH terms: Heart Ventricles/physiopathology*
  4. Fulltext Ageing in Pgc-1β-/- mice modelling mitochondrial dysfunction induces differential expression of a range of genes regulating ventricular electrophysiology
    Edling CE, Fazmin IT, Chadda KR, Ahmad S, Valli H, Grace AA, et al.
    Biosci Rep, 2019 04 30;39(4).
    PMID: 30914453 DOI: 10.1042/BSR20190127
    Mice deficient in mitochondrial promoter peroxisome proliferator activated receptor-γ co-activator-1β (Pgc-1β-/- ) is a valuable model for metabolic diseases and has been found to present with several pathologies including ventricular arrhythmia. In the present study, our aim was to shed light on the molecular mechanisms behind the observed arrhythmic substrate by studying how the expression of selected genes critical for cardiac function differs in wild-type (WT) compared with Pgc-1β knockout mice and young compared with aged mice. We found that a clear majority of genes are down-regulated in the Pgc-1β-/- ventricular tissue compared with the WT. Although most individual genes are not significantly differentially expressed, a pattern is apparent when the genes are grouped according to their functional properties. Genes encoding proteins relating to ATPase activity, potassium ion channels relating to repolarisation and resting membrane potential, and genes encoding proteins in the cAMP pathway are found to be significantly down-regulated in the Pgc-1β deficient mice. On the contrary, the pacemaker channel genes Hcn3 and Hcn4 are up-regulated in subsets of the Pgc-1β deficient tissue. Furthermore, we found that with age, especially in the Pgc-1β-/- genotype, most genes are up-regulated including genes relating to the resting membrane potential, calcium homeostasis, the cAMP pathway, and most of the tested adrenoceptors. In conclusion, we here demonstrate how a complex pattern of many modest changes at gene level may explain major functional differences of the action potential related to ageing and mitochondrial dysfunction.
    Matched MeSH terms: Heart Ventricles/physiopathology
  5. Effect of spatial inlet velocity profiles on the vortex formation pattern in a dilated left ventricle
    Chan BT, Lim E, Ong CW, Abu Osman NA
    Comput Methods Biomech Biomed Engin, 2015;18(1):90-6.
    PMID: 23521137 DOI: 10.1080/10255842.2013.779683
    Despite the advancement of cardiac imaging technologies, these have traditionally been limited to global geometrical measurements. Computational fluid dynamics (CFD) has emerged as a reliable tool that provides flow field information and other variables essential for the assessment of the cardiac function. Extensive studies have shown that vortex formation and propagation during the filling phase acts as a promising indicator for the diagnosis of the cardiac health condition. Proper setting of the boundary conditions is crucial in a CFD study as they are important determinants, that affect the simulation results. In this article, the effect of different transmitral velocity profiles (parabolic and uniform profile) on the vortex formation patterns during diastole was studied in a ventricle with dilated cardiomyopathy (DCM). The resulting vortex evolution pattern using the uniform inlet velocity profile agreed with that reported in the literature, which revealed an increase in thrombus risk in a ventricle with DCM. However the application of a parabolic velocity profile at the inlet yields a deviated vortical flow pattern and overestimates the propagation velocity of the vortex ring towards the apex of the ventricle. This study highlighted that uniform inlet velocity profile should be applied in the study of the filling dynamics in a left ventricle because it produces results closer to that observed experimentally.
    Matched MeSH terms: Heart Ventricles/physiopathology*
  6. Review on CFD simulation in heart with dilated cardiomyopathy and myocardial infarction
    Chan BT, Lim E, Chee KH, Abu Osman NA
    Comput Biol Med, 2013 May;43(4):377-85.
    PMID: 23428371 DOI: 10.1016/j.compbiomed.2013.01.013
    The heart is a sophisticated functional organ that plays a crucial role in the blood circulatory system. Hemodynamics within the heart chamber can be indicative of exert cardiac health. Due to the limitations of current cardiac imaging modalities, computational fluid dynamics (CFD) have been widely used for the purposes of cardiac function assessment and heart disease diagnosis, as they provide detailed insights into the cardiac flow field. An understanding of ventricular hemodynamics and pathological severities can be gained through studies that employ the CFD method. In this research the hemodynamics of two common myocardial diseases, dilated cardiomyopathy (DCM) and myocardial infarction (MI) were investigated, during both the filling phase and the whole cardiac cycle, through a prescribed geometry and fluid structure interaction (FSI) approach. The results of the research indicated that early stage disease identification and the improvement of cardiac assisting devices and therapeutic procedures can be facilitated through the use of the CFD method.
    Matched MeSH terms: Heart Ventricles/physiopathology
  7. Patient selection, pacing indications, and subsequent outcomes with de novo leadless single-chamber VVI pacing
    Piccini JP, Stromberg K, Jackson KP, Kowal RC, Duray GZ, El-Chami MF, et al.
    Europace, 2019 Nov 01;21(11):1686-1693.
    PMID: 31681964 DOI: 10.1093/europace/euz230
    AIMS: Patient selection is a key component of securing optimal patient outcomes with leadless pacing. We sought to describe and compare patient characteristics and outcomes of Micra patients with and without a primary pacing indication associated with atrial fibrillation (AF) in the Micra IDE trial.

    METHODS AND RESULTS: The primary outcome (risk of cardiac failure, pacemaker syndrome, or syncope related to the Micra system or procedure) was compared between successfully implanted patients from the Micra IDE trial with a primary pacing indication associated with AF or history of AF (AF group) and those without (non-AF group). Among 720 patients successfully implanted with Micra, 228 (31.7%) were in the non-AF group. Reasons for selecting VVI pacing in non-AF patients included an expectation for infrequent pacing (66.2%) and advanced age (27.2%). More patients in the non-AF group had a condition that precluded the use of a transvenous pacemaker (9.6% vs. 4.7%, P = 0.013). Atrial fibrillation patients programmed to VVI received significantly more ventricular pacing compared to non-AF patients (median 67.8% vs. 12.6%; P 

    Matched MeSH terms: Heart Ventricles/physiopathology*
  8. Fulltext Performance of a novel left ventricular lead with short bipolar spacing for cardiac resynchronization therapy: primary results of the Attain Performa quadripolar left ventricular lead study
    Crossley GH, Biffi M, Johnson B, Lin A, Gras D, Hussin A, et al.
    Heart Rhythm, 2015 Apr;12(4):751-8.
    PMID: 25533587 DOI: 10.1016/j.hrthm.2014.12.019
    The Medtronic Attain Performa quadripolar leads provide 16 pacing vectors with steroid on every electrode. This includes a short bipolar configuration between the middle 2 electrodes.
    Matched MeSH terms: Heart Ventricles/physiopathology
  9. Novel active fixation mechanism permits precise placement of a left ventricular lead: early results from a multicenter clinical study
    Yee R, Gadler F, Hussin A, Bin Omar R, Khaykin Y, Verma A, et al.
    Heart Rhythm, 2014 Jul;11(7):1150-5.
    PMID: 24801899 DOI: 10.1016/j.hrthm.2014.04.020
    Left ventricular (LV) lead implantation for cardiac resynchronization therapy (CRT) is associated with lead dislodgement rates ranging from 3% to 10%, and some implant approaches to prevent dislodgement may contribute to suboptimal CRT response. We report our early human experience with an LV lead with a side helix for active fixation to the coronary vein wall.
    Matched MeSH terms: Heart Ventricles/physiopathology
  10. Fulltext Predictors of atrial mechanical sensing and atrioventricular synchrony with a leadless ventricular pacemaker: Results from the MARVEL 2 Study
    Garweg C, Khelae SK, Steinwender C, Chan JYS, Ritter P, Johansen JB, et al.
    Heart Rhythm, 2020 12;17(12):2037-2045.
    PMID: 32717315 DOI: 10.1016/j.hrthm.2020.07.024
    BACKGROUND: The MARVEL (Micra Atrial TRacking Using a Ventricular AccELerometer) 2 study assessed the efficacy of atrioventricular (AV) synchronous pacing with a Micra leadless pacemaker. Average atrioventricular synchrony (AVS) was 89.2%. Previously, low amplitude of the Micra-sensed atrial signal (A4) was observed to be a factor of low AVS.

    OBJECTIVE: The purpose of this study was to identify predictors of A4 amplitude and high AVS.

    METHODS: We analyzed 64 patients enrolled in MARVEL 2 who had visible P waves on electrocardiogram for assessing A4 amplitude and 40 patients with third-degree AV block for assessing AVS at rest. High AVS was defined as >90% correct atrial-triggered ventricular pacing. The association between clinical factors and echocardiographic parameters with A4 amplitude was investigated using a multivariable model with lasso variable selection. Variables associated with A4 amplitude together with premature ventricular contraction burden, sinus rate, and sinus rate variability (standard deviation of successive differences of P-P intervals [SDSD]) were assessed for association with AVS.

    RESULTS: In univariate analysis, low A4 amplitude was inversely related to atrial function assessed by E/A ratio and e'/a' ratio, and was directly related to atrial contraction excursion (ACE) and atrial strain (Ɛa) on echocardiography (all P ≤.05). The multivariable lasso regression model found coronary artery bypass graft history, E/A ratio, ACE, and Ɛa were associated with low A4 amplitude. E/A ratio and SDSD were multivariable predictors of high AVS, with >90% probability if E/A <0.94 and SDSD <5 bpm.

    CONCLUSION: Clinical parameters and echocardiographic markers of atrial function are associated with A4 signal amplitude. High AVS can be predicted by E/A ratio <0.94 and low sinus rate variability at rest.

    Matched MeSH terms: Heart Ventricles/physiopathology*
  11. Fulltext Accelerometer-based atrioventricular synchronous pacing with a ventricular leadless pacemaker: Results from the Micra atrioventricular feasibility studies
    Chinitz L, Ritter P, Khelae SK, Iacopino S, Garweg C, Grazia-Bongiorni M, et al.
    Heart Rhythm, 2018 09;15(9):1363-1371.
    PMID: 29758405 DOI: 10.1016/j.hrthm.2018.05.004
    BACKGROUND: Micra is a leadless pacemaker that is implanted in the right ventricle and provides rate response via a 3-axis accelerometer (ACC). Custom software was developed to detect atrial contraction using the ACC enabling atrioventricular (AV) synchronous pacing.

    OBJECTIVE: The purpose of this study was to sense atrial contractions from the Micra ACC signal and provide AV synchronous pacing.

    METHODS: The Micra Accelerometer Sensor Sub-Study (MASS) and MASS2 early feasibility studies showed intracardiac accelerations related to atrial contraction can be measured via ACC in the Micra leadless pacemaker. The Micra Atrial TRacking Using A Ventricular AccELerometer (MARVEL) study was a prospective multicenter study designed to characterize the closed-loop performance of an AV synchronous algorithm downloaded into previously implanted Micra devices. Atrioventricular synchrony (AVS) was measured during 30 minutes of rest and during VVI pacing. AVS was defined as a P wave visible on surface ECG followed by a ventricular event <300 ms.

    RESULTS: A total of 64 patients completed the MARVEL study procedure at 12 centers in 9 countries. Patients were implanted with a Micra for a median of 6.0 months (range 0-41.4). High-degree AV block was present in 33 patients, whereas 31 had predominantly intrinsic conduction during the study. Average AVS during AV algorithm pacing was 87.0% (95% confidence interval 81.8%-90.9%), 80.0% in high-degree block patients and 94.4% in patients with intrinsic conduction. AVS was significantly greater (P

    Matched MeSH terms: Heart Ventricles/physiopathology*
  12. The role of infarct transmural extent in infarct extension: A computational study
    Leong CN, Lim E, Andriyana A, Al Abed A, Lovell NH, Hayward C, et al.
    Int J Numer Method Biomed Eng, 2017 Feb;33(2).
    PMID: 27043925 DOI: 10.1002/cnm.2794
    Infarct extension, a process involving progressive extension of the infarct zone (IZ) into the normally perfused border zone (BZ), leads to continuous degradation of the myocardial function and adverse remodelling. Despite carrying a high risk of mortality, detailed understanding of the mechanisms leading to BZ hypoxia and infarct extension remains unexplored. In the present study, we developed a 3D truncated ellipsoidal left ventricular model incorporating realistic electromechanical properties and fibre orientation to examine the mechanical interaction among the remote, infarct and BZs in the presence of varying infarct transmural extent (TME). Localized highly abnormal systolic fibre stress was observed at the BZ, owing to the simultaneous presence of moderately increased stiffness and fibre strain at this region, caused by the mechanical tethering effect imposed by the overstretched IZ. Our simulations also demonstrated the greatest tethering effect and stress in BZ regions with fibre direction tangential to the BZ-remote zone boundary. This can be explained by the lower stiffness in the cross-fibre direction, which gave rise to a greater stretching of the IZ in this direction. The average fibre strain of the IZ, as well as the maximum stress in the sub-endocardial layer, increased steeply from 10% to 50% infarct TME, and slower thereafter. Based on our stress-strain loop analysis, we found impairment in the myocardial energy efficiency and elevated energy expenditure with increasing infarct TME, which we believe to place the BZ at further risk of hypoxia. Copyright © 2016 John Wiley & Sons, Ltd.
    Matched MeSH terms: Heart Ventricles/physiopathology
  13. The role of end-diastolic myocardial fibre stretch on infarct extension
    Leong CN, Dokos S, Andriyana A, Liew YM, Chan BT, Abdul Aziz YF, et al.
    Int J Numer Method Biomed Eng, 2020 01;36(1):e3291.
    PMID: 31799767 DOI: 10.1002/cnm.3291
    Myocardial infarct extension, a process involving the enlargement of infarct and border zone, leads to progressive degeneration of left ventricular (LV) function and eventually gives rise to heart failure. Despite carrying a high risk, the causation of infarct extension is still a subject of much speculation. In this study, patient-specific LV models were developed to investigate the correlation between infarct extension and impaired regional mechanics. Subsequently, sensitivity analysis was performed to examine the causal factors responsible for the impaired regional mechanics observed in regions surrounding the infarct and border zone. From our simulations, fibre strain, fibre stress and fibre stress-strain loop (FSSL) were the key biomechanical variables affected in these regions. Among these variables, only FSSL was correlated with infarct extension, as reflected in its work density dissipation (WDD) index value, with high WDD indices recorded at regions with infarct extension. Impaired FSSL is caused by inadequate contraction force generation during the isovolumic contraction and ejection phases. Our further analysis revealed that the inadequacy in contraction force generation is not necessarily due to impaired myocardial intrinsic contractility, but at least in part, due to inadequate muscle fibre stretch at end-diastole, which depresses the ability of myocardium to generate adequate contraction force in the subsequent systole (according to the Frank-Starling law). Moreover, an excessively stiff infarct may cause its neighbouring myocardium to be understretched at end-diastole, subsequently depressing the systolic contractile force of the neighbouring myocardium, which was found to be correlated with infarct extension.
    Matched MeSH terms: Heart Ventricles/physiopathology
  14. Fulltext Atrioventricular Synchronous Pacing Using a Leadless Ventricular Pacemaker: Results From the MARVEL 2 Study
    Steinwender C, Khelae SK, Garweg C, Chan JYS, Ritter P, Johansen JB, et al.
    JACC Clin Electrophysiol, 2020 01;6(1):94-106.
    PMID: 31709982 DOI: 10.1016/j.jacep.2019.10.017
    OBJECTIVES: This study reports on the performance of a leadless ventricular pacemaker with automated, enhanced accelerometer-based algorithms that provide atrioventricular (AV) synchronous pacing.

    BACKGROUND: Despite many advantages, leadless pacemakers are currently only capable of single-chamber ventricular pacing.

    METHODS: The prospective MARVEL 2 (Micra Atrial tRacking using a Ventricular accELerometer 2) study assessed the performance of an automated, enhanced accelerometer-based algorithm downloaded to the Micra leadless pacemaker for up to 5 h in patients with AV block. The primary efficacy objective was to demonstrate the superiority of the algorithm to provide AV synchronous (VDD) pacing versus VVI-50 pacing in patients with sinus rhythm and complete AV block. The primary safety objective was to demonstrate that the algorithm did not result in pauses or heart rates of >100 beats/min.

    RESULTS: Overall, 75 patients from 12 centers were enrolled; an accelerometer-based algorithm was downloaded to their leadless pacemakers. Among the 40 patients with sinus rhythm and complete AV block included in the primary efficacy objective analysis, the proportion of patients with ≥70% AV synchrony at rest was significantly greater with VDD pacing than with VVI pacing (95% vs. 0%; p 

    Matched MeSH terms: Heart Ventricles/physiopathology*
  15. Drawbacks in using hypercapnic acidosis in preoperative children with single ventricle physiology
    Prakash ES
    J Appl Physiol (1985), 2008 06;104(6):1841.
    PMID: 18584792 DOI: 10.1152/japplphysiol.zdg-7979-pcpcomm.2008
    Matched MeSH terms: Heart Ventricles/physiopathology
  16. Left ventricular flow propagation velocity measurement: Is it cast in stone?
    Chan BT, Yeoh HK, Liew YM, Aziz YFA, Sridhar GS, Hamilton-Craig C, et al.
    Med Biol Eng Comput, 2017 Oct;55(10):1883-1893.
    PMID: 28321684 DOI: 10.1007/s11517-017-1639-5
    This study aims to investigate the measurement of left ventricular flow propagation velocity, V p, using phase contrast magnetic resonance imaging and to assess the discrepancies resulting from inflow jet direction and individual left ventricular size. Three V p measuring techniques, namely non-adaptive (NA), adaptive positions (AP) and adaptive vectors (AV) method, were suggested and compared. We performed the comparison on nine healthy volunteers and nine post-infarct patients at four measurement positions, respectively, at one-third, one-half, two-thirds and the conventional 4 cm distances from the mitral valve leaflet into the left ventricle. We found that the V p measurement was affected by both the inflow jet direction and measurement positions. Both NA and AP methods overestimated V p, especially in dilated left ventricles, while the AV method showed the strongest correlation with the isovolumic relaxation myocardial strain rate (r = 0.53, p 
    Matched MeSH terms: Heart Ventricles/physiopathology*
  17. Fulltext The RyR2-P2328S mutation downregulates Nav1.5 producing arrhythmic substrate in murine ventricles
    Ning F, Luo L, Ahmad S, Valli H, Jeevaratnam K, Wang T, et al.
    Pflugers Arch., 2016 Apr;468(4):655-65.
    PMID: 26545784 DOI: 10.1007/s00424-015-1750-0
    Catecholaminergic polymorphic ventricular tachycardia (CPVT) predisposes to ventricular arrhythmia due to altered Ca(2+) homeostasis and can arise from ryanodine receptor (RyR2) mutations including RyR2-P2328S. Previous reports established that homozygotic murine RyR2-P2328S (RyR2 (S/S)) hearts show an atrial arrhythmic phenotype associated with reduced action potential (AP) conduction velocity and sodium channel (Nav1.5) expression. We now relate ventricular arrhythmogenicity and slowed AP conduction in RyR2 (S/S) hearts to connexin-43 (Cx43) and Nav1.5 expression and Na(+) current (I Na). Stimulation protocols applying extrasystolic S2 stimulation following 8 Hz S1 pacing at progressively decremented S1S2 intervals confirmed an arrhythmic tendency despite unchanged ventricular effective refractory periods (VERPs) in Langendorff-perfused RyR2 (S/S) hearts. Dynamic pacing imposing S1 stimuli then demonstrated that progressive reductions of basic cycle lengths (BCLs) produced greater reductions in conduction velocity at equivalent BCLs and diastolic intervals in RyR2 (S/S) than WT, but comparable changes in AP durations (APD90) and their alternans. Western blot analyses demonstrated that Cx43 protein expression in whole ventricles was similar, but Nav1.5 expression in both whole tissue and membrane fractions were significantly reduced in RyR2 (S/S) compared to wild-type (WT). Loose patch-clamp studies similarly demonstrated reduced I Na in RyR2 (S/S) ventricles. We thus attribute arrhythmogenesis in RyR2 (S/S) ventricles resulting from arrhythmic substrate produced by reduced conduction velocity to downregulated Nav1.5 reducing I Na, despite normal determinants of repolarization and passive conduction. The measured changes were quantitatively compatible with earlier predictions of linear relationships between conduction velocity and the peak I Na of the AP but nonlinear relationships between peak I Na and maximum Na(+) permeability.
    Matched MeSH terms: Heart Ventricles/physiopathology
  18. Fulltext Effects of ageing on pro-arrhythmic ventricular phenotypes in incrementally paced murine Pgc-1β -/- hearts
    Ahmad S, Valli H, Edling CE, Grace AA, Jeevaratnam K, Huang CL
    Pflugers Arch., 2017 Dec;469(12):1579-1590.
    PMID: 28821956 DOI: 10.1007/s00424-017-2054-3
    A range of chronic clinical conditions accompany cardiomyocyte energetic dysfunction and constitute independent risk factors for cardiac arrhythmia. We investigated pro-arrhythmic and arrhythmic phenotypes in energetically deficient C57BL mice with genetic ablation of the mitochondrial promoter peroxisome proliferator-activated receptor-γ coactivator-1β (Pgc-1β), a known model of ventricular arrhythmia. Pro-arrhythmic and cellular action potential (AP) characteristics were compared in intact Langendorff-perfused hearts from young (12-16 week) and aged (> 52 week), wild-type (WT) and Pgc-1β -/- mice. Simultaneous electrocardiographic and intracellular microelectrode recordings were made through successive trains of 100 regular stimuli at progressively incremented heart rates. Aged Pgc-1β -/- hearts displayed an increased incidence of arrhythmia compared to other groups. Young and aged Pgc-1β -/- hearts showed higher incidences of alternans in both AP activation (maximum AP upshoot velocity (dV/dt)max and latency), recovery (action potential duration (APD90) and resting membrane potential (RMP) characteristics compared to WT hearts. This was particularly apparent at lower pacing frequencies. These findings accompanied reduced (dV/dt)max and increased AP latency values in the Pgc-1β -/- hearts. APs observed prior to termination of the protocol showed lower (dV/dt)max and longer AP latencies, but indistinguishable APD90 and RMPs in arrhythmic compared to those in non-arrhythmic hearts. APD restitution analysis showed that Pgc-1β -/- and WT hearts showed similar limiting gradients. However, Pgc-1β -/- hearts had shortened plateau AP wavelengths, particularly in aged Pgc-1β -/- hearts. Pgc-1β -/- hearts therefore show pro-arrhythmic instabilities attributable to altered AP conduction and activation rather than recovery characteristics.
    Matched MeSH terms: Heart Ventricles/physiopathology
  19. Fulltext An inverse finite element method for determining the tissue compressibility of human left ventricular wall during the cardiac cycle
    Hassaballah AI, Hassan MA, Mardi AN, Hamdi M
    PLoS One, 2013;8(12):e82703.
    PMID: 24367544 DOI: 10.1371/journal.pone.0082703
    The determination of the myocardium's tissue properties is important in constructing functional finite element (FE) models of the human heart. To obtain accurate properties especially for functional modeling of a heart, tissue properties have to be determined in vivo. At present, there are only few in vivo methods that can be applied to characterize the internal myocardium tissue mechanics. This work introduced and evaluated an FE inverse method to determine the myocardial tissue compressibility. Specifically, it combined an inverse FE method with the experimentally-measured left ventricular (LV) internal cavity pressure and volume versus time curves. Results indicated that the FE inverse method showed good correlation between LV repolarization and the variations in the myocardium tissue bulk modulus K (K = 1/compressibility), as well as provided an ability to describe in vivo human myocardium material behavior. The myocardium bulk modulus can be effectively used as a diagnostic tool of the heart ejection fraction. The model developed is proved to be robust and efficient. It offers a new perspective and means to the study of living-myocardium tissue properties, as it shows the variation of the bulk modulus throughout the cardiac cycle.
    Matched MeSH terms: Heart Ventricles/physiopathology*
  20. Fulltext Sensitivity analysis of left ventricle with dilated cardiomyopathy in fluid structure simulation
    Chan BT, Abu Osman NA, Lim E, Chee KH, Abdul Aziz YF, Abed AA, et al.
    PLoS One, 2013;8(6):e67097.
    PMID: 23825628 DOI: 10.1371/journal.pone.0067097
    Dilated cardiomyopathy (DCM) is the most common myocardial disease. It not only leads to systolic dysfunction but also diastolic deficiency. We sought to investigate the effect of idiopathic and ischemic DCM on the intraventricular fluid dynamics and myocardial wall mechanics using a 2D axisymmetrical fluid structure interaction model. In addition, we also studied the individual effect of parameters related to DCM, i.e. peak E-wave velocity, end systolic volume, wall compliance and sphericity index on several important fluid dynamics and myocardial wall mechanics variables during ventricular filling. Intraventricular fluid dynamics and myocardial wall deformation are significantly impaired under DCM conditions, being demonstrated by low vortex intensity, low flow propagation velocity, low intraventricular pressure difference (IVPD) and strain rates, and high-end diastolic pressure and wall stress. Our sensitivity analysis results showed that flow propagation velocity substantially decreases with an increase in wall stiffness, and is relatively independent of preload at low-peak E-wave velocity. Early IVPD is mainly affected by the rate of change of the early filling velocity and end systolic volume which changes the ventriculo:annular ratio. Regional strain rate, on the other hand, is significantly correlated with regional stiffness, and therefore forms a useful indicator for myocardial regional ischemia. The sensitivity analysis results enhance our understanding of the mechanisms leading to clinically observable changes in patients with DCM.
    Matched MeSH terms: Heart Ventricles/physiopathology*
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