ResearchPad - cardiac-pacing https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Is transjugular insertion of a temporary pacemaker a safe and effective approach?]]> https://www.researchpad.co/article/elastic_article_13814 Temporary pacemakers (TPMs) are usually inserted in an emergency situation. However, there are few reports available regarding which route of access is best or what the most preferred approach is currently in tertiary hospitals. This study aimed to compare procedure times, complication rates, and indications for temporary pacing between the transjugular and transfemoral approaches to TPM placement. We analyzed consecutive patients who underwent TPM placement. Indications; procedure times; and rates of complications including localized infection, any bleeding, and pacing wire repositioning rates were analyzed. A total of 732 patients (361 treated via the transjugular approach and 371 treated via the transfemoral approach) were included. Complete atrioventricular block was the most common cause of TPM placement in both groups, but sick sinus syndrome was especially common in the transjugular approach group. Separately, procedure time was significantly shorter in the transjugular approach group (9.0 ± 8.0 minutes vs. 11.9 ± 9.7 minutes; P < 0.001). Overall complication rates were not significantly different between the two groups, and longer duration of temporary pacing was a risk factor for repositioning. The risk of reposition was significantly increased when the temporary pacing was continued more than 5 days and 3 days in the transjugular approach group and the transfemoral approach group, respectively. The transjugular approach should be considered if the TPM is required for more than 3 days.

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<![CDATA[Outcomes of cardiac resynchronization therapy in patients with atrial fibrillation accompanied by slow ventricular response]]> https://www.researchpad.co/article/5c424385d5eed0c4845e0487

It remains unclear as to whether cardiac resynchronization therapy (CRT) would be as effective in patients with atrial fibrillation (AF) accompanied by slow ventricular response (AF-SVR, < 60 beats/min) as in those with sinus rhythm (SR). Echocardiographic reverse remodeling was compared between AF-SVR patients (n = 17) and those with SR (n = 88) at six months and 12 months after CRT treatment. We also evaluated the changes in QRS duration; New York Heart Association (NYHA) functional class; and long-term composite clinical outcomes including cardiac death, heart transplantation, and heart failure (HF)-related hospitalization. Left ventricular pacing sites and biventricular pacing percentages were not significantly different between the AF-SVR and SR groups. However, heart rate increase after CRT was significantly greater in the AF-SVR group than in the SR group (P < 0.001). At six and 12 months postoperation, both groups showed a comparable improvement in NYHA class; QRS narrowing; and echocardiographic variables including left ventricular end-systolic volume, left ventricular ejection fraction, and left atrial volume index. Over the median follow-up duration of 1.6 (interquartile range: 0.8–2.2) years, no significant between-group differences were observed regarding the rates of long-term composite clinical events (35% versus 24%; hazard ratio: 1.71; 95% confidence interval: 0.23–12.48; P = 0.60). CRT implantation provided comparable beneficial effects for patients with AF-SVR as compared with those with SR, by correcting electrical dyssynchrony and increasing biventricular pacing rate, in terms of QRS narrowing, symptom improvement, ventricular reverse remodeling, and long-term clinical outcomes.

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<![CDATA[Effect of increasing heart rate on finger photoplethysmography fitness index (PPGF) in subjects with implanted cardiac pacemakers]]> https://www.researchpad.co/article/5c084236d5eed0c484fcc339

Finger photoplethysmography (PPG) is a noninvasive method that measures blood volume changes in the finger. The PPG fitness index (PPGF) has been proposed as an index of vascular risk and vascular aging. The objectives of the study were to determine the effects of heart rate (HR) on the PPGF and to determine whether PPGF is influenced by blood pressure (BP) changes. Twenty subjects (78±8 years, 3 female) with permanent cardiac pacemakers or cardioverter defibrillators were prospectively recruited. HR was changed by pacing, in a random order from 60 to 100 bpm and in 10 bpm increments. At each paced HR, the PPGF was derived from a finger photoplethysmogram. Cardiac output (CO), stroke volume (SV) and total peripheral resistance (TPR) were derived from the finger arterial pressure waveform. Brachial blood pressure (BP) was measured by the oscillometric method. This study found that as HR was increased from 60 to 100 bpm, brachial diastolic BP, brachial mean BP and CO were significantly increased (p<0.01), whilst the PPGF and SV were significantly decreased (p<0.001). The effects of HR on the PPGF were influenced by BP, with a decreasing HR effect on the PPGF that resulted from a higher BP. In conclusion, HR was a significant confounder for PPGF and it must be taken into account in analyses of PPGF, when there are large changes or differences in the HR. The magnitude of this effect was BP dependent.

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<![CDATA[In Heart Failure Patients with Left Bundle Branch Block Single Lead MultiSpot Left Ventricular Pacing Does Not Improve Acute Hemodynamic Response To Conventional Biventricular Pacing. A Multicenter Prospective, Interventional, Non-Randomized Study]]> https://www.researchpad.co/article/5989d9d8ab0ee8fa60b66a51

Introduction

Recent efforts to increase CRT response by multiSPOT pacing (MSP) from multiple bipols on the same left ventricular lead are still inconclusive.

Aim

The Left Ventricular (LV) MultiSPOTpacing for CRT (iSPOT) study compared the acute hemodynamic response of MSP pacing by using 3 electrodes on a quadripolar lead compared with conventional biventricular pacing (BiV).

Methods

Patients with left bundle branch block (LBBB) underwent an acute hemodynamic study to determine the %change in LV+dP/dtmax from baseline atrial pacing compared to the following configurations: BiV pacing with the LV lead in a one of lateral veins, while pacing from the distal, mid, or proximal electrode and all 3 electrodes together (i.e. MSP). All measurements were repeated 4 times at 5 different atrioventricular delays. We also measured QRS-width and individual Q-LV durations.

Results

Protocol was completed in 24 patients, all with LBBB (QRS width 171±20 ms) and 58% ischemic aetiology. The percentage change in LV+dP/dtmax for MSP pacing was 31.0±3.3% (Mean±SE), which was not significantly superior to any BiV pacing configuration: 28.9±3.2% (LV-distal), 28.3±2.7% (LV-mid), and 29.5±3.0% (LV-prox), respectively. Correlation between LV+dP/dtmax and either QRS-width or Q-LV ratio was poor.

Conclusions

In patients with LBBB MultiSPOT LV pacing demonstrated comparable improvement in contractility to best conventional BiV pacing. Optimization of atrioventricular delay is important for the best performance for both BiV and MultiSPOT pacing configurations.

Trial Registration

ClinicalTrials.gov NTC01883141

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<![CDATA[One-Month Global Longitudinal Strain Identifies Patients Who Will Develop Pacing-Induced Left Ventricular Dysfunction over Time: The Pacing and Ventricular Dysfunction (PAVD) Study]]> https://www.researchpad.co/article/5989dad9ab0ee8fa60bb90ae

Background

Predicting which individuals will have a decline in left ventricular (LV) function after pacemaker implantation remains an important challenge. We investigated whether LV global longitudinal strain (GLS), measured by 2D speckle tracking strain echocardiography, can identify patients at risk of pacing-induced left ventricular dysfunction (PIVD) or pacing-induced cardiomyopathy (PICMP).

Methods

Fifty-five patients with atrioventricular block and preserved LV function underwent dual-chamber pacemaker implantation and were followed with serial transthoracic echocardiography for 12 months for the development of PIVD (defined as a reduction in LV ejection fraction (LVEF) ≥5 percentage points at 12 months) or PICMP (reduction in LVEF to <45%).

Results

At 12 months, 15 (27%) patients developed PIVD; of these, 4 patients developed PICMP. At one month, GLS was significantly lower in the 15 patients who subsequently developed PIVD, compared to those who did not (n = 40) (GLS -12.6 vs. -16.4 respectively; p = 0.022). When patients with PICMP were excluded, one month GLS was significantly reduced compared to baseline whereas LVEF was not. One-month GLS had high predictive accuracy for determining subsequent development of PIVD or PICMP (AUC = 0.80, optimal GLS threshold: <−14.5, sensitivity 82%, specificity 75%); and particularly PICMP (AUC = 0.86, optimal GLS threshold: <−13.5, sensitivity 100%, specificity 71%).

Conclusions

GLS is a novel predictor of decline in LV systolic function following pacemaker implantation, with the potential to identify patients at risk of PIVD before measurable changes in LVEF are apparent. GLS measured one month after implantation has high predictive accuracy for identifying patients who later develop PIVD or PICMP.

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<![CDATA[Hepatocyte Growth Factor Modification Enhances the Anti-Arrhythmic Properties of Human Bone Marrow-Derived Mesenchymal Stem Cells]]> https://www.researchpad.co/article/5989da35ab0ee8fa60b861f6

Background/Aims

Chronic myocardial infarction (MI) results in the formation of arrhythmogenic substrates, causing lethal ventricular arrhythmia (VA). We aimed to determine whether mesenchymal stem cells (MSCs) carrying a hepatocyte growth factor (HGF) gene modification (HGF-MSCs) decrease the levels of arrhythmogenic substrates and reduce the susceptibility to developing VA compared with unmodified MSCs and PBS in a swine infarction model.

Methods

The left descending anterior artery was balloon-occluded to establish an MI model. Four weeks later, the randomly grouped pigs were administered MSCs, PBS or HGF-MSCs via thoracotomy. After an additional four weeks, dynamic electrocardiography was performed to assess heart rate variability, and programmed electrical stimulation was conducted to evaluate the risk for VA. Then, the pigs were euthanized for morphometric, immunofluorescence and western blot analyses. Results: The HGF-MSC group displayed the highest vessel density and Cx43 expression levels, and the lowest levels of apoptosis, and tyrosine hydroxylase (TH) and growth associated protein 43 (GAP43) expression. Moreover, the HGF-MSC group exhibited a decrease in the number of sympathetic nerve fibers, substantial decreases in the low frequency and the low-/high- frequency ratio and increases in the root mean square of successive differences (rMSSD) and the percentage of successive normal sinus R-R intervals longer than 50 ms (pNN50), compared with the other two groups. Finally, the HGF-MSC group displayed the lowest susceptibility to developing VA.

Conclusion

HGF-MSCs displayed potent antiarrhythmic effects, reducing the risk for VA.

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<![CDATA[Acute Impact of Pacing at Different Cardiac Sites on Left Ventricular Rotation and Twist in Dogs]]> https://www.researchpad.co/article/5989daacab0ee8fa60ba9d07

Objectives

We evaluated the acute impact of different cardiac pacing sites on two-dimensional speckle-tracking echocardiography (STE) derived left ventricular (LV) rotation and twist in healthy dogs.

Methods

Twelve dogs were used in this study. The steerable pacing electrodes were positioned into right heart through the superior or inferior vena cava, into LV through aorta across the aortic valve. The steerable pacing electrodes were positioned individually in the right atrium (RA), right ventricular apex (RVA), RV outflow tract (RVOT), His bundle (HB), LV apex (LVA) and LV high septum (LVS), individual pacing mode was applied at 10 minutes interval for at least 5 minutes from each position under fluoroscopy and ultrasound guidance and at stabilized hemodynamic conditions. LV short-axis images at the apical and basal levels were obtained during sinus rhythm and pacing. Offline STE analysis was performed. Rotation, twist, time to peak rotation (TPR), time to peak twist (TPT), and apical-basal rotation delay (rotational synchronization index, RSI) values were compared at various conditions. LV pressure was monitored simultaneously.

Results

Anesthetic death occurred in 1 dog, and another dog was excluded because of bad imaging quality. Data from 10 dogs were analyzed. RVA, RVOT, HB, LVA, LVS, RARV (RA+RVA) pacing resulted in significantly reduced apical and basal rotation and twist, significantly prolonged apical TPR, TPT and RSI compared to pre-pacing and RA pacing (all P<0.05). The apical and basal rotation and twist values were significantly higher during HB pacing than during pacing at ventricular sites (all P<0.05, except basal rotation at RVA pacing). The apical TPR during HB pacing was significantly shorter than during RVOT and RVA pacing (both P<0.05). The LV end systolic pressure (LVESP) was significantly lower during ventricular pacing than during pre-pacing and RA pacing.

Conclusions

Our results show that RA and HB pacing results in less acute reduction on LV twist, rotation and LVESP compared to ventricular pacing.

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<![CDATA[Spatial Characterization of Electrogram Morphology from Transmural Recordings in the Intact Normal Heart]]> https://www.researchpad.co/article/5989dae1ab0ee8fa60bbbfea

Purpose

Unipolar (UE) and bipolar electrograms (BE) are utilized to identify arrhythmogenic substrate. We quantified the effect of increasing distance from the source of propagation on local electrogram amplitude; and determined if transmural electrophysiological gradients exist with respect to propagation and stimulation depth.

Methods

Mapping was performed on 5 sheep. Deployment of >50 quadripolar transmural needles in the LV were located in Cartesian space using Ensite. Contact electrograms from all needles were recorded during multisite bipolar pacing from epicardial then endocardial electrodes. Analysis was performed to determine stimulus distance to local activation time, peak negative amplitude (V-P), and peak-peak amplitude (VP-P) for (1) unfiltered UE, and (2) unfiltered and 30 Hz high-pass filtered BEs. Each sheep was analysed using repeated ANOVA.

Results

Increasing distance from the pacing sites led to significant (p<0.01) attenuation of UEs (V-P = 7.0±0.5%; VP-P = 5.4±0.3% per cm). Attenuation of BE with distance was insignificant (Vp-p unfiltered  = 2.2±0.5%; filtered  = 1.7±1.4% per cm). Independent of pacing depth, significant (p<0.01) transmural electrophysiological gradients were observed, with highest amplitude occurring at epicardial layers for UE and endocardial layers for BE. Furthermore, during pacing, propagation was earlier at the epicardium than endocardial layer by 1.6±2.0 ms (UE) and 1.4±2.8 ms (BE) (all p>0.01) during endocardial stimulation, and 2.3±2.4 ms (UE) and 1.8±3.7 ms (BE) during epicardal stimulation (all p<0.01).

Conclusions

Electrogram amplitude is inversely proportional to propagation distance for unipolar modalities only, which affected V-P>VP-P. Conduction propagates preferentially via the epicardium during stimulation and is believed to contribute to a transmural amplitude gradient.

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<![CDATA[A Regional Reduction in Ito and IKACh in the Murine Posterior Left Atrial Myocardium Is Associated with Action Potential Prolongation and Increased Ectopic Activity]]> https://www.researchpad.co/article/5989da0dab0ee8fa60b78576

Background

The left atrial posterior wall (LAPW) is potentially an important area for the development and maintenance of atrial fibrillation. We assessed whether there are regional electrical differences throughout the murine left atrial myocardium that could underlie regional differences in arrhythmia susceptibility.

Methods

We used high-resolution optical mapping and sharp microelectrode recordings to quantify regional differences in electrical activation and repolarisation within the intact, superfused murine left atrium and quantified regional ion channel mRNA expression by Taqman Low Density Array. We also performed selected cellular electrophysiology experiments to validate regional differences in ion channel function.

Results

Spontaneous ectopic activity was observed during sustained 1Hz pacing in 10/19 intact LA and this was abolished following resection of LAPW (0/19 resected LA, P<0.001). The source of the ectopic activity was the LAPW myocardium, distinct from the pulmonary vein sleeve and LAA, determined by optical mapping. Overall, LAPW action potentials (APs) were ca. 40% longer than the LAA and this region displayed more APD heterogeneity. mRNA expression of Kcna4, Kcnj3 and Kcnj5 was lower in the LAPW myocardium than in the LAA. Cardiomyocytes isolated from the LAPW had decreased Ito and a reduced IKACh current density at both positive and negative test potentials.

Conclusions

The murine LAPW myocardium has a different electrical phenotype and ion channel mRNA expression profile compared with other regions of the LA, and this is associated with increased ectopic activity. If similar regional electrical differences are present in the human LA, then the LAPW may be a potential future target for treatment of atrial fibrillation.

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<![CDATA[Patient-Specific Human Induced Pluripotent Stem Cell Model Assessed with Electrical Pacing Validates S107 as a Potential Therapeutic Agent for Catecholaminergic Polymorphic Ventricular Tachycardia]]> https://www.researchpad.co/article/5989d9efab0ee8fa60b6dfe9

Introduction

Human induced pluripotent stem cells (hiPSCs) offer a unique opportunity for disease modeling. However, it is not invariably successful to recapitulate the disease phenotype because of the immaturity of hiPSC-derived cardiomyocytes (hiPSC-CMs). The purpose of this study was to establish and analyze iPSC-based model of catecholaminergic polymorphic ventricular tachycardia (CPVT), which is characterized by adrenergically mediated lethal arrhythmias, more precisely using electrical pacing that could promote the development of new pharmacotherapies.

Method and Results

We generated hiPSCs from a 37-year-old CPVT patient and differentiated them into cardiomyocytes. Under spontaneous beating conditions, no significant difference was found in the timing irregularity of spontaneous Ca2+ transients between control- and CPVT-hiPSC-CMs. Using Ca2+ imaging at 1 Hz electrical field stimulation, isoproterenol induced an abnormal diastolic Ca2+ increase more frequently in CPVT- than in control-hiPSC-CMs (control 12% vs. CPVT 43%, p<0.05). Action potential recordings of spontaneous beating hiPSC-CMs revealed no significant difference in the frequency of delayed afterdepolarizations (DADs) between control and CPVT cells. After isoproterenol application with pacing at 1 Hz, 87.5% of CPVT-hiPSC-CMs developed DADs, compared to 30% of control-hiPSC-CMs (p<0.05). Pre-incubation with 10 μM S107, which stabilizes the closed state of the ryanodine receptor 2, significantly decreased the percentage of CPVT-hiPSC-CMs presenting DADs to 25% (p<0.05).

Conclusions

We recapitulated the electrophysiological features of CPVT-derived hiPSC-CMs using electrical pacing. The development of DADs in the presence of isoproterenol was significantly suppressed by S107. Our model provides a promising platform to study disease mechanisms and screen drugs.

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<![CDATA[Left ventricular long axis tissue Doppler systolic velocity is independently related to heart rate and body size]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdbe46

Background

The physiological factors which affect left ventricular (LV) long-axis function are not fully defined. We investigated the relationships of resting heart rate and body size with the peak velocities and amplitudes of LV systolic and early diastolic long axis motion, and also with long-axis contraction duration.

Methods

Two groups of adults free of cardiac disease underwent pulsed-wave tissue Doppler imaging at the septal and lateral mitral annular borders. Group 1 (n = 77) were healthy subjects <50 years of age and Group 2 (n = 65) were subjects between 40–80 years of age referred for stress echocardiography. Systolic excursion (SExc), duration (SDur) and peak velocity (s') and early diastolic excursion (EDExc) and peak velocity (e') were measured.

Results

SExc was not correlated with heart rate, height or body surface area (BSA) for either LV wall in either group, but SDur was inversely correlated with heart rate for both walls and both groups, and after adjustment for heart rate, males in both groups had a shorter septal SDur. Septal and lateral s` were independently and positively correlated with SExc, heart rate and height in both groups, independent of sex and age. There were no correlations of heart rate, height or BSA with either e` or EDExc for either wall in either group.

Conclusion

Heart rate and height independently modify the relationship between s` and SExc, but neither are related to EDExc or e`. These findings suggest that s` and SExc cannot be used interchangeably for the assessment of LV long-axis contraction.

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<![CDATA[Interactions between Activation and Repolarization Restitution Properties in the Intact Human Heart: In-Vivo Whole-Heart Data and Mathematical Description]]> https://www.researchpad.co/article/5989db43ab0ee8fa60bd7a58

Background

The restitution of the action potential duration (APDR) and conduction velocity (CVR) are mechanisms whereby cardiac excitation and repolarization adapt to changes in heart rate. They modulate the vulnerability to dangerous arrhythmia, but the mechanistic link between restitution and arrhythmogenesis remains only partially understood.

Methods

This paper provides an experimental and theoretical study of repolarization and excitation restitution properties and their interactions in the intact human epicardium. The interdependence between excitation and repolarization dynamic is studied in 8 patients (14 restitution protocols, 1722 restitution curves) undergoing global epicardial mapping with multi-electrode socks before open heart surgery. A mathematical description of the contribution of both repolarization and conduction dynamics to the steepness of the APDR slope is proposed.

Results

This study demonstrates that the APDR slope is a function of both activation and repolarization dynamics. At short cycle length, conduction delay significantly increases the APDR slope by interacting with the diastolic interval. As predicted by the proposed mathematical formulation, the APDR slope was more sensitive to activation time prolongation than to the simultaneous shortening of repolarization time. A steep APDR slope was frequently identified, with 61% of all cardiac sites exhibiting an APDR slope > 1, suggesting that a slope > 1 may not necessarily promote electrical instability in the human epicardium. APDR slope did not change for different activation or repolarization times, and it was not a function of local baseline APD. However, it was affected by the spatial organization of electrical excitation, suggesting that in tissue APDR is not a unique function of local electrophysiological properties. Spatial heterogeneity in both activation and repolarization restitution contributed to the increase in the modulated dispersion of repolarization, which for short cycle length was as high as 250 ms. Heterogeneity in conduction velocity restitution can translate into both activation and repolarization dispersion and increase cardiac instability. The proposed mathematical formulation shows an excellent agreement with the experimental data (correlation coefficient r = 0.94) and provides a useful tool for the understanding of the complex interactions between activation and repolarization restitution properties as well as between their measurements.

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<![CDATA[Heart Rate Dependence of the Pulmonary Resistance x Compliance (RC) Time and Impact on Right Ventricular Load]]> https://www.researchpad.co/article/5989da64ab0ee8fa60b918d4

Background

The effect of heart rate (HR) and body surface area (BSA) on pulmonary RC time and right ventricular (RV) load is unknown.

Methods

To determine the association of HR and BSA with the pulmonary RC time and measures of RV load, we studied three large patient cohorts including subjects with 1) known or suspected pulmonary arterial hypertension (PAH) (n = 1008), 2) pulmonary hypertension due to left heart disease (n = 468), and 3) end-stage heart failure with reduced ejection fraction (n = 150). To corroborate these associations on an individual patient level, we performed an additional analysis using high-fidelity catheters in 22 patients with PAH undergoing right atrial pacing.

Results

A faster HR inversely correlated with RC time (p<0.01 for all), suggesting augmented RV pulsatile loading. Lower BSA directly correlated with RC time (p<0.05) although the magnitude of this effect was smaller than for HR. With incremental atrial pacing, cardiac output increased and total pulmonary resistance (TPR) fell. However, effective arterial elastance, its mean resistive component (TPR/heart period; 0.60±0.27 vs. 0.79±0.45;p = 0.048), and its pulsatile component (0.27±0.18 vs 0.39±0.28;p = 0.03) all increased at faster HR.

Conclusion

Heart rate and BSA are associated with pulmonary RC time. As heart rate increases, the pulsatile and total load on the RV also increase. This relationship supports a hemodynamic mechanism for adverse effects of tachycardia on the RV.

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<![CDATA[A Mathematical Model of Neonatal Rat Atrial Monolayers with Constitutively Active Acetylcholine-Mediated K+ Current]]> https://www.researchpad.co/article/5989d9d6ab0ee8fa60b65ff7

Atrial fibrillation (AF) is the most frequent form of arrhythmia occurring in the industrialized world. Because of its complex nature, each identified form of AF requires specialized treatment. Thus, an in-depth understanding of the bases of these arrhythmias is essential for therapeutic development. A variety of experimental studies aimed at understanding the mechanisms of AF are performed using primary cultures of neonatal rat atrial cardiomyocytes (NRAMs). Previously, we have shown that the distinct advantage of NRAM cultures is that they allow standardized, systematic, robust re-entry induction in the presence of a constitutively-active acetylcholine-mediated K+ current (IKACh-c). Experimental studies dedicated to mechanistic explorations of AF, using these cultures, often use computer models for detailed electrophysiological investigations. However, currently, no mathematical model for NRAMs is available. Therefore, in the present study we propose the first model for the action potential (AP) of a NRAM with constitutively-active acetylcholine-mediated K+ current (IKACh-c). The descriptions of the ionic currents were based on patch-clamp data obtained from neonatal rats. Our monolayer model closely mimics the action potential duration (APD) restitution and conduction velocity (CV) restitution curves presented in our previous in vitro studies. In addition, the model reproduces the experimentally observed dynamics of spiral wave rotation, in the absence and in the presence of drug interventions, and in the presence of localized myofibroblast heterogeneities.

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<![CDATA[Interactions of Calcium Fluctuations during Cardiomyocyte Contraction with Real-Time cAMP Dynamics Detected by FRET]]> https://www.researchpad.co/article/5989da7cab0ee8fa60b98f70

Calcium (Ca2+) and 3’,5’-cyclic adenosine monophosphate (cAMP) play a critical role for cardiac excitation-contraction-coupling. Both second messengers are known to interact with each other, for example via Ca2+-dependent modulation of phosphodiesterase 1 (PDE1) and adenylyl cyclase 5/6 (AC 5/6) activities, which is supposed to occur especially at the local level in distinct subcellular microdomains. Currently, many studies analyze global and local cAMP signaling and its regulation in resting cardiomyocytes devoid of electrical stimulation. For example, Förster resonance energy transfer (FRET) microscopy is a popular approach for visualization of real time cAMP dynamics performed in resting cardiomyocytes to avoid potential contractility-related movement artifacts. However, it is unknown whether such data are comparable with the cell behavior under more physiologically relevant conditions during contraction. Here, we directly compare the cAMP-FRET responses to AC stimulation and PDE inhibition in resting vs. paced adult mouse ventricular cardiomyocytes for both cytosolic and subsarcolemmal microdomains. Interestingly, no significant differences in cAMP dynamics could be detected after β-adrenergic (isoproterenol) stimulation, suggesting low impact of rapidly changing contractile Ca2+ concentrations on cytosolic cAMP levels associated with AC activation. However, the contribution of the calcium-dependent PDE1, but not of the Ca2+-insensitive PDE4, to the regulation of cAMP levels after forskolin stimulation was significantly increased. This increase could be mimicked by pretreatment of resting cells with Ca2+ elevating agents. Ca2+ imaging demonstrated significantly higher amplitudes of Ca2+ transients in forskolin than in isoproterenol stimulated cells, suggesting that forskolin stimulation might lead to stronger activation of PDE1. In conclusion, changes in intracellular Ca2+ during cardiomyocyte contraction dynamically interact with cAMP levels, especially after strong AC stimulation. The use of resting cells for FRET-based measurements of cAMP can be justified under β-adrenergic stimulation, while the reliable analysis of PDE1 effects may require electric field stimulation.

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<![CDATA[Feasibility of In-Vivo Simulation of Acute Hemodynamics in Human Atrial Fibrillation]]> https://www.researchpad.co/article/5989da1bab0ee8fa60b7cd6b

This study evaluated hemodynamic feasibility and reproducibility of a new method for in vivo simulation of human atrial fibrillation (AF). The method was tested during sinus rhythm in 10 patients undergoing catheter ablation for AF. A simple electronic device was assembled that allowed triggering a cardiac stimulator by predefined series of RR intervals. Irregular RR interval sequences with a mean heart rate of 90/min and 130/min were obtained from ECG recordings of another patients with AF. Simultaneous atrioventricular pacing was delivered by catheters placed inside the coronary sinus and at the His bundle region. Hemodynamic effect of the simulated AF was assessed by invasive measurement of the left ventricular (LV) pressure, dP/dt, and Tau. Compared to regular pacing at the same mean heart rate, the simulated AF significantly impaired the LV both systolic and diastolic function. Repeated AF pacing in the same patients generated similar LV hemodynamics. The proposed method provides a realistic and reproducible in-vivo model of AF. It can be exploited for investigation of the hemodynamic consequences of AF in various patient populations.

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<![CDATA[Recent heart rate history affects QT interval duration in atrial fibrillation]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdbe85

QT interval prolongation is associated with a risk of polymorphic ventricular tachycardia. QT interval shortens with increasing heart rate and correction for this effect is necessary for meaningful QT interval assessment. We aim to improve current methods of correcting the QT interval during atrial fibrillation (AF). Digitized Holter recordings were analyzed from patients with AF. Models of QT interval dependence on RR intervals were tested by sorting the beats into 20 bins based on corrected RR interval and assessing ST-T variability within the bins. Signal-averaging within bins was performed to determine QT/RR dependence. Data from 30 patients (29 men, 69.3±7.3 years) were evaluated. QT behavior in AF is well described by a linear function (slope ~0.19) of steady-state corrected RR interval. Corrected RR is calculated as a combination of an exponential weight function with time-constant of 2 minutes and a smaller “immediate response” component (weight ~ 0.18). This model performs significantly (p<0.0001) better than models based on instantaneous RR interval only including Bazett and Fridericia. It also outperforms models based on shorter time-constants and other previously proposed models. This model may improve detection of repolarization delay in AF. QT response to heart rate changes in AF is similar to previously published QT dynamics during atrial pacing and in sinus rhythm.

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<![CDATA[Can Pacing Be Regulated by Post-Activation Potentiation? Insights from a Self-Paced 30 km Trial in Half-Marathon Runners]]> https://www.researchpad.co/article/5989da8cab0ee8fa60b9e30c

Purpose

Given the co-existence of post-activation potentiation (PAP) and fatigue within muscle, it is not known whether PAP could influence performance and pacing during distance running by moderating fatigue. The aim of this study was to assess the influence of PAP on pacing, jumping and other physiological measures during a self-paced 30 km trial.

Methods

Eleven male endurance-trained runners (half-marathon runners) volunteered to participate in this study. Runners participated in a multi-stage 30 km trial. Before the trial started, determination of baseline blood lactate (bLa) and countermovement jump (CMJ) height was performed. The self-paced 30 km trial consisted of 6 × 5 km splits. At the end of each 5 km split (60 s break), data on time to complete the split, CMJ height, Rating of Perceived Exertion (RPE) and blood lactate were collected while heart rate was continuously monitored.

Results

There was a significant decrease in speed (e.g. positive pacing strategy after the 4th split, p<0.05) with a progressive increase in RPE throughout the trial. Compared with baseline, CMJ height was significantly (p<0.05) greater than baseline and was maintained until the end of the trial with an increase after the 5th split, concomitant with a significant reduction in speed and an increase in RPE. Significant correlations were found between ΔCMJ and ΔSPEED (r = 0.77 to 0.87, p<0.05) at different time points as well as between RPE and speed (r = -0.61 to -0.82, p<0.05).

Conclusion

Our results indicates that fatigue and potentiation co-exist during long lasting endurance events, and that the observed increase in jump performance towards the end of the trial could be reflecting a greater potentiation potentially perhaps counteracting the effects of fatigue and preventing further reductions in speed.

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<![CDATA[A Low-Cost Simulation Model for R-Wave Synchronized Atrial Pacing in Pediatric Patients with Postoperative Junctional Ectopic Tachycardia]]> https://www.researchpad.co/article/5989da02ab0ee8fa60b74a1e

Background

Postoperative junctional ectopic tachycardia (JET) occurs frequently after pediatric cardiac surgery. R-wave synchronized atrial (AVT) pacing is used to re-establish atrioventricular synchrony. AVT pacing is complex, with technical pitfalls. We sought to establish and to test a low-cost simulation model suitable for training and analysis in AVT pacing.

Methods

A simulation model was developed based on a JET simulator, a simulation doll, a cardiac monitor, and a pacemaker. A computer program simulated electrocardiograms. Ten experienced pediatric cardiologists tested the model. Their performance was analyzed using a testing protocol with 10 working steps.

Results

Four testers found the simulation model realistic; 6 found it very realistic. Nine claimed that the trial had improved their skills. All testers considered the model useful in teaching AVT pacing. The simulation test identified 5 working steps in which major mistakes in performance test may impede safe and effective AVT pacing and thus permitted specific training. The components of the model (exclusive monitor and pacemaker) cost less than $50. Assembly and training-session expenses were trivial.

Conclusions

A realistic, low-cost simulation model of AVT pacing is described. The model is suitable for teaching and analyzing AVT pacing technique.

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<![CDATA[TRPC4α and TRPC4β Similarly Affect Neonatal Cardiomyocyte Survival during Chronic GPCR Stimulation]]> https://www.researchpad.co/article/5989da6fab0ee8fa60b9419e

The Transient Receptor Potential Channel Subunit 4 (TRPC4) has been considered as a crucial Ca2+ component in cardiomyocytes promoting structural and functional remodeling in the course of pathological cardiac hypertrophy. TRPC4 assembles as homo or hetero-tetramer in the plasma membrane, allowing a non-selective Na+ and Ca2+ influx. Gαq protein-coupled receptor (GPCR) stimulation is known to increase TRPC4 channel activity and a TRPC4-mediated Ca2+ influx which has been regarded as ideal Ca2+ source for calcineurin and subsequent nuclear factor of activated T-cells (NFAT) activation. Functional properties of TRPC4 are also based on the expression of the TRPC4 splice variants TRPC4α and TRPC4β. Aim of the present study was to analyze cytosolic Ca2+ signals, signaling, hypertrophy and vitality of cardiomyocytes in dependence on the expression level of either TRPC4α or TRPC4β. The analysis of Ca2+ transients in neonatal rat cardiomyocytes (NRCs) showed that TRPC4α and TRPC4β affected Ca2+ cycling in beating cardiomyocytes with both splice variants inducing an elevation of the Ca2+ transient amplitude at baseline and TRPC4β increasing the Ca2+ peak during angiotensin II (Ang II) stimulation. NRCs infected with TRPC4β (Ad-C4β) also responded with a sustained Ca2+ influx when treated with Ang II under non-pacing conditions. Consistent with the Ca2+ data, NRCs infected with TRPC4α (Ad-C4α) showed an elevated calcineurin/NFAT activity and a baseline hypertrophic phenotype but did not further develop hypertrophy during chronic Ang II/phenylephrine stimulation. Down-regulation of endogenous TRPC4α reversed these effects, resulting in less hypertrophy of NRCs at baseline but a markedly increased hypertrophic enlargement after chronic agonist stimulation. Ad-C4β NRCs did not exhibit baseline calcineurin/NFAT activity or hypertrophy but responded with an increased calcineurin/NFAT activity after GPCR stimulation. However, this effect was not translated into an increased propensity towards hypertrophy but rather less hypertrophy during GPCR stimulation. Further analyses revealed that, although hypertrophy was preserved in Ad-C4α NRCs and even attenuated in Ad-C4β NRCs, cardiomyocytes had an increased apoptosis rate and thus were less viable after chronic GPCR stimulation. These findings suggest that TRPC4α and TRPC4β differentially affect Ca2+ signals, calcineurin/NFAT signaling and hypertrophy but similarly impair cardiomyocyte viability during GPCR stimulation.

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