Continuous ECG Recordings Research Articles

Paroxysmal atrial fibrillation prediction based on morphological variant P-wave analysis with wideband ECG and deep learning

Background and objectiveAtrial fibrillation (AF) is one of the most frequent asymptomatic arrhythmias associated with significant morbidity and mortality. Identifying the susceptibility to AF based on routine or continuous ECG recording is of considerable interest. Despite several P-wave characteristics and skin sympathetic nerve activity (SKNA) linked to AF onset, neither factor has offered accurate predictability. We propose a deep learning enabled method for AF risk prediction. MethodsWe develop a novel MVPNet to predict the upcoming onset of paroxysmal AF. MVPNet combines wavelet-based feature extraction and a deep learning classifier. MVPNet detect the approaching of AF onset by analyzing the template and frequency in P-wave segments. The morphological variant P-wave (MVP) analysis includes P-wave and SKNA features cross temporal-spectral domain. Subsequently, we designed an optimized lightweight convolutional neural network model to detect the MVP features of pre-AF episodes during sinus rhythm segments. Wideband ECG data obtained through the neuECG protocol from eight PAF patients with 177 times AF occurrence in this study. We compared the accuracy of AF prediction between ordinary ECG and neuECG. ResultsThe MVPNet effectively predicted the onset of AF episodes. 89% of ECG recorded at 5 min before the AF onset can be identified using neuECG. The proposed deep learning model, MVPNet, obtained a better precision and inference speed with less computing resources than existing models. The gradient activation map showed that neuECG recording may be a superior AF risk predictor. ConclusionsMVP analysis combined SKNA and P-wave parameters to improve predictive accuracy. The proposed MVPNet based on neuECG is superior to existing AF risk assessment with improved reliability and effectiveness. The method can be potentially applied in clinical scenarios for real-time, continuous AF prediction.

Reduced Cell Excitability of Cardiac Postganglionic Parasympathetic Neurons Correlates With Myocardial Infarction-Induced Fatal Ventricular Arrhythmias in Type 2 Diabetes Mellitus

ObjectiveWithdrawal of cardiac vagal activity is considered as one of the important triggers for acute myocardial infarction (MI)-induced ventricular arrhythmias in type 2 diabetes mellitus (T2DM). Our previous study demonstrated that cell excitability of cardiac parasympathetic postganglionic (CPP) neurons was reduced in T2DM rats. This study investigated whether cell excitability of CPP neurons is associated with cardiac vagal activity and MI-induced ventricular arrhythmias in T2DM rats.MethodsRat T2DM was induced by a high-fat diet plus streptozotocin injection. MI-evoked ventricular arrhythmia was achieved by surgical ligation of the left anterior descending coronary artery. Twenty-four-hour, continuous ECG recording was used to quantify ventricular arrhythmic events and heart rate variability (HRV) in conscious rats. The power spectral analysis of HRV was used to evaluate autonomic function. Cell excitability of CPP neurons was measured by the whole-cell patch-clamp technique.ResultsTwenty-four-hour ECG data demonstrated that MI-evoked fatal ventricular arrhythmias are more severe in T2DM rats than that in sham rats. In addition, the Kaplan-Meier analysis demonstrated that the survival rate over 2 weeks after MI is significantly lower in T2DM rats (15% in T2DM+MI) compared to sham rats (75% in sham+MI). The susceptibility to ventricular tachyarrhythmia elicited by programmed electrical stimulation was higher in anesthetized T2DM+MI rats than that in rats with MI or T2DM alone (7.0 ± 0.58 in T2DM+MI group vs. 3.5 ± 0.76 in sham+MI). Moreover, as an index for vagal control of ventricular function, changes of left ventricular systolic pressure (LVSP) and the maximum rate of increase of left ventricular pressure (LV dP/dtmax) in response to vagal efferent nerve stimulation were blunted in T2DM rats. Furthermore, T2DM increased heterogeneity of ventricular electrical activities and reduced cardiac parasympathetic activity and cell excitability of CPP neurons (current threshold-inducing action potentials being 62 ± 3.3 pA in T2DM rats without MI vs. 27 ± 1.9 pA in sham rats without MI). However, MI did not alter vagal control of the ventricular function and CPP neuronal excitability, although it also induced cardiac autonomic dysfunction and enhanced heterogeneity of ventricular electrical activities.ConclusionThe reduction of CPP neuron excitability is involved in decreased cardiac vagal function, including cardiac parasympathetic activity and vagal control of ventricular function, which is associated with MI-induced high mortality and malignant ventricular arrhythmias in T2DM.

B-PO03-186 MONITORING ATRIAL FIBRILLATION PATIENTS USING ACTIVE CONTACTLESS VIDEOPLESTHYMOGRAPHY IMPLEMENTED ON A PERSONAL TABLET

Early detection of subclinical AF can help prevent significant complications such as embolic stroke, heart failure, and AF-related hospitalizations. We evaluated the performance of a facial pulsation detection video technology called videoplethysmography (VPG) to detect the presence of AF using a monitoring method that does not require a dedicated sensor and/or cumbersome recording procedures. We enrolled patients with AF undergoing either cardioversion or ablation therapy. Patients were asked to collect two 25-sec video recordings daily using a smart tablet loaded with the VPG technology. Early recurrence of AF during the 15-day follow-up period was based on continuous ECG recording (14-day patch monitor). ECGs were manually annotated for the presence of AF episodes lasting >15-sec in duration. The VPG algorithm measured pulse irregularity and was designed to minimize false positive detections. Development and validation were performed on independent datasets (½ split without a subject in common). We report the specificity, sensitivity, and accuracy of the video-based method to detect early recurrence of AF during the follow-up period. The motion of the patient's face was tracked, but no feedback was provided to the subjects during the measurement. We enrolled 112 patients (age: 65∓9 years, 81 men) over an 18 month period. Five subjects did not collect any quality data while 107 patients collected 7∓5 minutes of data on average at home (min:30sec, max: 25min) over 12∓3 days (min:1.5, max:14.7 days). Thirty subjects (28%) experienced at least one 15-sec AF episode post-procedure. The sensitivity and specificity of the AF detection algorithm based on a total duration of 7 min. of video recordings, over 12 days were 33% and 95% in the validation dataset (accuracy: 74%). Less than one-minute daily monitoring using a contactless VPG method can detect AF in one-third of patients experiencing an early recurrence of AF with a 5% false-positive rate. The sensitivity of the VPG method is expected to increase with a larger number of daily VPG recordings.

Melatonin Treatment Does Not Modify Ectopic Activity During Ischemia and Reperfusion in Rats

Introduction Ventricular tachycardia and/or ventricular fibrillation (VT/VF), a life-threatening complication of acute myocardial ischemia are based on the interaction between a vulnerable arrhythmogenic substrate and an arrhythmic trigger. Melatonin was proposed as a potential antiarrhythmic medication and was shown to ameliorate the arrhythmogenic substrate. Also, melatonin provides a sympatholytic effect and thereby can attenuate ectopic activity, which provides the triggers for VT/VF. However, little is known about a melatonin effect on the arrhythmic triggering. In the present study, we aimed at evaluation of the melatonin effects on catecholamine synthesis in normal and ischemic myocardium and heart rhythm disturbances during an episode of ischemia and reperfusion. Methods Experiments were done in 30 control and 32 melatonin-treated (10 mg/kg, daily, for 7 days) male rats. The hearts from 10 control and 10 treated animals were taken for histochemical analysis of sympathetic fibers (glyoxylic acid-induced fluorescence). Continuous ECG recording was performed in 20 control and 22 treated anesthetized animals before and during an ischemia-reperfusion episode induced by reversible 5-min occlusion of the left anterior descending coronary artery. Tyrosine hydroxylase expression in normal and ischemic myocardial regions was assessed by Western blotting analysis in 12 control and 12 melatonin-treated animals. Results No differences in the state of sympathetic innervation (density and fluorescence intensity) were observed in histochemical analysis. However, Western blotting demonstrated that melatonin treatment suppressed tyrosine hydroxylase expression in normal (p<0.05 vs control) but not in ischemic regions of myocardium. Melatonin-treated animals had longer RR-intervals in the baseline state, but this difference progressively disappeared during the period of ischemia due to tachycardic response to ischemia in the treated group (Figure). No differences in the number of extrasystoles were found between the control and treated groups during ischemia and reperfusion periods (Figure). Conclusion Chronic melatonin treatment led to the peripheral sympatholytic effect in myocardium, which was associated with decreased heart rate in preischemic conditions. However, this effect attenuated during ischemia and no differences in heart rate or extrasystolic burden were found between the control and treated animals during ischemia and reperfusion.

Environmentally relevant secondhand smoke and time‐dependent changes in cardiovascular regulation in mice

BACKGROUND Secondhand smoke (SHS), a significant source of indoor air pollution, is a significant risk factor for cardiovascular morbidity and mortality. SHS-induced autonomic dysfunction, evidenced as increased sympathetic nerve activity and decreased heart rate variability (HRV), has been implicated as an important underlying mechanism for cardiovascular consequences. Previously, we have demonstrated that acute exposure (3 d) to 30 mg/m3 of SHS was sufficient to reduce HRV in mice. Here, we sought to characterize the time course of SHS-induced changes to cardiovascular regulation resulting from chronic exposure to environmentally relevant SHS (3 mg/m3). METHODS Male C57BL/6J mice (11 wk) implanted with BP/ECG telemetry devices were exposed to either filtered air (FA, n=18) or SHS (3 mg/m3, 6 hr/d, 5 d/wk, n=17) for 12 weeks, followed by 4 weeks of FA (representing a SHS “recovery” window). Monthly, 36 hours of continuous BP and ECG recordings were obtained during non-exposure days. Data were divided into three 12-hour periods: The dark cycle (dark 1) immediately after the 5th day of exposure, and the following light and dark (dark 2) cycles. Spontaneous baroreflex sensitivity (BRS) was determined with the sequence method. Standard time domain HRV parameters were obtained during periods of low activity. RESULTS SHS decreased overall HRV (SDNN) during the dark 1 cycle (-15%, -7%, and -28% for 4, 8, and 12 wk, respectively, p < 0.05). Similarly, SHS significantly reduced short-term HRV (rMSSD) during the dark 1 cycle (-16%, -12%, and -20% for 4, 8, and 12 wk, respectively, p < 0.05). SHS exposure did not affect HRV beyond the initial 12 hours after exposure ended (light and dark 2 cycles). These data suggest that SHS attenuates cardiac vagal regulation. SHS also reduced pulse pressure (~2 mmHg, p < 0.05) for the entire 36-hr recording window after 4, 8, and 12 wks of exposure, an effect that persisted even after 4 wks of recovery. There was a trend for lower BRS after 12 wks of SHS exposure during the dark 1 cycle. Intriguingly, initial exposure to SHS significantly elevated diastolic BP (~3 mmHg) during the dark 1 cycle at 4 wks; this effect was not observed with longer exposure to SHS (8 or 12 wks). Taken together, these data suggest that SHS exposure poses a greater risk to cardiac function than vascular function, and that vasculature regulation may be more protected from SHS-induced autonomic effects. CONCLUSIONS Chronic SHS reduces autonomic regulation of the cardiovascular function, particularly the regulation of the heart. Except for reduced pulse pressure, these autonomic effects were transient, and reversed themselves in the absence of SHS exposure, underscoring the importance and efficacy of public smoking bans.

Dlouhodobá EKG monitorace

ECG recording represents an essential method for the diagnosis of heart rhythm disturbances. Long-term monitoring helps to identify arrhythmias that have not been detected by means of standard 12-lead ECG or 24-48 hour ECG Holter. With time, ECG monitoring facilities improve, the ECG recorders are becoming smaller, and the recording time is prolonging. At present, continuous ECG recording is generally available. Smart watches and fitness bracelets further expand monitoring options in patients with known or suspected arrhythmia. Individual type and frequency of symptoms remain the most significant criterion for the selection of suitable ECG recorder and recording time.

The Number of Frames on ECG-Gated 18F-FDG Small Animal PET Has a Significant Impact on LV Systolic and Diastolic Functional Parameters.

Objectives This study is aimed at investigating the impact of frame numbers in preclinical electrocardiogram- (ECG-) gated 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) on systolic and diastolic left ventricular (LV) parameters in rats. Methods 18F-FDG PET imaging using a dedicated small animal PET system with list mode data acquisition and continuous ECG recording was performed in diabetic and control rats. The list-mode data was sorted and reconstructed with different numbers of frames (4, 8, 12, and 16) per cardiac cycle into tomographic images. Using an automatic ventricular edge detection software, left ventricular (LV) functional parameters, including ejection fraction (EF), end-diastolic (EDV), and end-systolic volume (ESV), were calculated. Diastolic variables (time to peak filling (TPF), first third mean filling rate (1/3 FR), and peak filling rate (PFR)) were also assessed. Results Significant differences in multiple parameters were observed among the reconstructions with different frames per cardiac cycle. EDV significantly increased by numbers of frames (353.8 ± 57.7 μl∗, 380.8 ± 57.2 μl∗, 398.0 ± 63.1 μl∗, and 444.8 ± 75.3 μl at 4, 8, 12, and 16 frames, respectively; ∗P < 0.0001 vs. 16 frames), while systolic (EF) and diastolic (TPF, 1/3 FR and PFR) parameters were not significantly different between 12 and 16 frames. In addition, significant differences between diabetic and control animals in 1/3 FR and PFR in 16 frames per cardiac cycle were observed (P < 0.005), but not for 4, 8, and 12 frames. Conclusions Using ECG-gated PET in rats, measurements of cardiac function are significantly affected by the frames per cardiac cycle. Therefore, if you are going to compare those functional parameters, a consistent number of frames should be used.

Continuous ECG Monitoring V. Mobile Telemetry: A Comparison of Arrhythmia Diagnostics

Introduction: A myriad of long-term (>48 hr) cardiac rhythm monitors are available for use. Clinicians rarely scrutinize the full disclosure and thus rely on manufacturers to detect and report relevant rhythm abnormalities using processes that are opaque to most providers. This study compares the diagnostic accuracy between mobile cardiac telemetry (MCT) and long term continuous ECG monitoring. Methods: In an outpatient arrhythmia clinic, 50 sequential patients ordered to wear a 30-day MCT were enrolled to simultaneously wear a continuous ECG monitor. Periods of concomitant wear of both devices were examined. Studies were reviewed by two electrophysiologists and categorized according to whether significant clinical arrhythmias were identified and correctly diagnosed. Results: Of the 50 patients enrolled, 46 wore both monitors simultaneously for an average time of simultaneous recording of 10.3 ± 4.4 days. During simultaneous recording, significant arrhythmias were diagnosed by the MCT in 11/46 patients (24%) compared with 23/46 (50%) patients p=0.018, by continuous ECG monitoring. Thus, in 12 of 46 patients (26%), a significant arrhythmia finding was captured by the long-term ECG and missed by the MCT. Long term continuous ECG captured several rhythms which were misreported or unreported by MCT including AV node re-entry in two patients, second degree AV block in three patients, VT in 6 patients, and captured 4 additional AF episodes missed by MCT. Conclusions: In a time-controlled, paired analysis of two disparate rhythm monitors worn simultaneously, human review of long-term continuous ECG recordings significantly outperformed algorithm-dependent MCT monitor's ability to detect significant arrhythmias.

Abstract 364: Continuous Electrocardiogram Classification During Resuscitation Using Transfer Learning

Introduction: Cardiac arrest resuscitation requires CPR interruption for ECG rhythm analysis, but pausing CPR is adversely associated with survival. Ideally, automated rhythm analysis would occur agnostic of CPR state throughout resuscitation and discriminate non-shockable from shockable rhythms. Transfer learning of pre-trained deep convolutional neural networks (CNNs) may enable accurate ECG analysis when applied to time-frequency representations of the ECG. We designed and evaluated a transfer learning algorithm to identify ventricular fibrillation (VF), asystole (AS), and organized (OR) rhythms agnostic of CPR. Methods: In this observational study of out-of-hospital cardiac arrest, rhythms were manually diagnosed in continuous defibrillator ECG recordings. Non-overlapping adjacent 2-s ECG segments were extracted from the first 30 min of each case regardless of CPR during VF, AS, and OR. Each segment was represented by an intrafrequency-normalized Morlet wavelet transform from 4-40 Hz. Using a 2/3 subset of patients for training, a series of two ResNet-101 CNNs were retrained to perform a shock decision (VF vs. non-shockable) followed by a specific non-shockable prediction (AS, OR, or Indeterminate). Performance was evaluated in a 1/3 validation subset of patients using a range of probability decision thresholds to predict the class of each segment. Results: In total, 275100 segments were collected from 461 patients. Of 90962 segments from 152 validation patients, using a 0.7 probability threshold for class prediction, 21% (18930/90962) were indeterminate, shock vs. no-shock sensitivity and specificity were 90% (19702/21930) and 97% (48421/50102), and specificities among non-shockable rhythms for AS vs. OR were 84% (5032/5998) and 86% (37760/44104), respectively (Fig 1). Conclusion: Transfer learning may enable shock/no-shock and rhythm-specific ECG classification continuously throughout resuscitation regardless of CPR.

Atrial fibrillation ablation – the value of AF burden monitoring in the long-term follow-up

Atrial fibrillation (AF) is the most common arrhythmia, increasing the risk of stroke and all-cause mortality, predominantly due to cardiovascular diseases. Catheter ablation (CA) is recommended therapy, with far better long-term outcome compared to antiarrhythmic medication, and prolonged cardiac monitoring is crucial in the post-ablation follow-up. Due to technology advancements, we can introduce not only more effective methods for invasive AF treatment, but also the valuation of its long-term outcome. Implantable cardiac monitors (ICMs) provide continuous ECG recording, required to assess the exact time of AF duration. AF burden, defined as the proportion of time an individual is in AF during the monitoring period is an excellent quantitative indicator for more complex evaluation of the AF ablation outcome, presenting it not merely as the binary effect.

224Wireless ECG embedded in a necklace enables reliable detection of atrial fibrillation

Abstract Funding Acknowledgements Goverment grant, Heart2save Ltd cooperation. Background/Introduction: Atrial fibrillation (AF) is the most common arrhythmia and a fast-growing public health problem worldwide. Main and the most severe complication of AF is an embolic stroke. Approximately 25% of all strokes are caused by AF. AF is often symptomless and intermittent, making its detection and diagnosing challenging. Many AF patients have both symptomatic and asymptomatic periods of arrhythmia. In addition, during the early stage of the disease, AF is often paroxysmal making the diagnosis of AF a major clinical challenge. Purpose Wearable ECG devices could enable repetitive rhythm monitoring over a long term and thus improve the probability of AF detection. Wearable devices have the advantage of being easily available. However, they also need to be reliable and their design should appeal customers. Our aim was to study the suitability and reliability of novel measurement technique (necklace-ECG, Figure1) for the diagnosis of AF. Methods The study population consisted of 145 adult volunteers at Kuopio University Hospital emergency department (66 AF and 79 sinus rhythm (SR), diagnosed from continuous 3-lead ECG recording. All study subjects performed a thirty-second self-performed ECG recording with a single-lead necklace-embedded ECG recorder (necklace-ECG) keeping the recorder between palms of their hands. The ECG recordings were analyzed with automatic AF detection algorithm. Two cardiologists interpreted independently in blinded fashion the necklace-ECG recordings and simultaneously registered 3-lead ECGs which served as golden standard for the final rhythm diagnosis. Results Necklace-ECG produced an interpretable ECG recording in 91.0%/86.2% patients (Doc1/Doc2, respectively). Additionally, 93.1% of ECG recordings were interpretable by the automatic analysis service (98.7% in SR patients and 86.4% of AF patients). Base on the necklace ECG recording, cardiologists were able to diagnose AF with sensitivity of 98.2%/96.3% (Doc1/Doc2, respectively) and specificity of 100% (Doc1 and Doc2, respectively). The automatic arrhythmia algorithm diagnosed AF with sensitivity of 94.7% and specificity of 100%. Conclusions The necklace-ECG device produces ECG recording with sufficient quality for the detection of AF with good sensitivity and specificity as evaluated both by cardiologist and automated AF-detection algorithm. Thus, wearable necklace-ECG provides a new and easy method for screening, identifying and diagnosing AF. Abstract Figure 1

CDK5 promotes ventricular arrhythmogenesis through phosphorylation of N‐type calcium channels in cardiac sympathetic postganglionic neurons

Cardiac sympathetic overactivation is an important trigger of fatal ventricular arrhythmias in patients with chronic heart failure (CHF). Our previous study found that increased N‐type calcium (Cav2.2) currents in cardiac sympathetic postganglionic (CSP) neurons contributes to cardiac sympathetic overactivation and ventricular arrhythmogenesis in CHF rats. Cyclin‐dependent kinase 5 (CDK5), a proline‐directed serine/threonine kinase, has been reported to play an important role in regulation of calcium influx and neurotransmitter release through phosphorylation of Cav2.2α subunit. Our current study aims to investigate whether CDK5 induces cardiac sympathetic overactivation and increases the susceptibility to ventricular arrhythmias via phosphorylation of Cav2.2α in CSP neurons. Lentiviral‐CDK5 cDNA (1×107 TU/ml, 2μl) was in vivo transfected into bilateral stellate ganglia (SG) in sham rats. Nontransfected sham rats served as controls. Final experiments were performed at 9 days after gene transfection. Western blot data demonstrated that gene transfection with lentiviral‐CDK5 cDNA into SGs significantly increased protein expression of CDK5 in CSP neurons in sham rats, compared with nontransfected sham rats. CDK5 cDNA transfection in SGs increased phosphorylation level of Cav 2.2α in CSP neurons from sham rat. The power spectral analysis of heart rate variability in conscious rats demonstrated that overexpression of CDK5 in CSP neurons increased low frequency power and ratio of low frequency to high frequency (index of cardiac sympathetic activation). Additionally, transfection of CDK5 cDNA into CSP neurons markedly increased cardiac sympathetic nerve activity in anesthetized sham rats (45.3±6.4% in sham+CDK5 group vs. 29.2±2.1% in sham group). ECG data obtained from 24‐hour continuous telemetry ECG recording revealed that overexpression of CDK5 in CSP neurons induced heterogeneity of ventricular electrical activities in conscious sham rats, as evidenced by CDK5 cDNA‐elongated ventricular arrhythmia‐related ECG markers including QT interval, QT dispersion, and T‐peak to T‐end interval. More importantly, transfection with CDK5 cDNA into CSP neurons significantly increased the susceptibility to ventricular arrhythmias (arrhythmia score was 1.7±0.9 in sham+CDK5 group vs. 0 in sham group) in anesthetized sham rats. Based on above data, we conclude that CDK5 induces cardiac sympathetic overactivation via phosphorylation of Cav 2.2‐α subunits in CSP neurons, and further increases the susceptibility of ventricular arrhythmias in sham rats.Support or Funding InformationThis study was supported by National Heart, Lung, and Blood Institute Grant (R01HL137832‐01 to Y.‐L. Li)

27 Cerebral Autoregulation Associated with Falls in Older Persons with Orthostatic Hypotension?

Abstract Background It is considered well-established that orthostatic hypotension (OH) is associated with falls, population-based studies have found that a large proportion of community-dwelling older adults fulfill the criteria for OH without experiencing falls. It is therefore postulated that older individuals with OH may only experience fall if cerebral autoregulation, which is the mechanism by which the brain blood flow is maintained constant through a autoregulatory range, is impaired. Objective To evaluate the relationship between cerebral autoregulation and OH in older individuals with and without a history of falls. Method Individuals aged 3 60 years were recruited from medical clinics, by word of mouth, and from existing research registries. Baseline sociodemographics, detailed medical history and medication history were obtained. Bilateral middle cerebral artery (MCA) blood flow were recorded using transcranial Doppler ultrasound (TCD) synchronized with non-invasive continuous blood pressure and ECG recordings. Synchronized brain blood flow signals, heart trace and blood pressure signals were first recorded during 10 minutes’ supine rest. Participants were then be asked to perform a standard set of mathematical calculations, a Valsalva maneuver and to stand up from a seated position. Results 36 participants have been evaluated to date (13 fallers, 23 non-Fallers). There is no statistically significant difference in gender, ethnicity or height and weight between groups. Fluctuations in MCA flow velocity were observed with spontaneous fluctuations in blood pressure at rest and with induced blood pressure changes during the challenge maneuvers. Visual inspection of the signals obtained suggested that changes in MCA flow velocity were more marked among fallers and non-fallers. Conclusion Synchronization of cerebral blood flow and continuous blood pressure signals opens up numerous new possibilities in research and clinical practice. Our preliminary findings suggest that cerebral autoregulation does play a role in determining the presence of symptomats in older individuals with OH.

Talazoparib has no clinically relevant effect on QTc interval in patients with advanced solid tumors.

The aims of this study were (i) to evaluate the effect of talazoparib (1 mg once daily) on cardiac repolarization in patients with advanced solid tumors by assessing corrected QT interval (QTc) and (ii) to examine the relationship between plasma talazoparib concentration and QTc. In this open-label phase 1 study, patients had continuous 12-lead ECG recordings at baseline followed by time-matched continuous ECG recordings and collection of talazoparib plasma pharmacokinetic samples predose and at 1, 2, 4, and 6 h postdose on treatment days 1 and 22 and before talazoparib administration on day 2. ECG recordings were submitted for independent central review where triplicate 10-s ECGs, extracted up to 15 min before pharmacokinetic samples, were assessed for RR, PR, QRS, and QT intervals and ECG morphology. QT interval was corrected for heart rate using Fridericia's (QTcF) and Bazett's (QTcB) formulae. Linear mixed-effects modeling was used to examine the relationship between QTc and RR interval change from baseline and plasma talazoparib concentration. Thirty-seven patients received talazoparib. Mean change in QTcF from time-matched baseline ranged from -3.5 to 6.9 ms, with the greatest change 1 h postdose on day 22. No clinically relevant changes in PR, QRS, QTcB, QTcF, or RR intervals, heart rate, or ECG morphology were observed. No concentration-dependent effect on heart rate or QTc was observed. No deaths, permanent treatment discontinuations due to adverse events were reported. Talazoparib (1 mg once daily) had no clinically relevant effects on cardiac repolarization.

Dietary Flaxseed Protects against Post‐Myocardial Infarction Arrhythmias and Injury

Dietary Ω‐3 polyunsaturated fatty acids (Ω‐3 PUFAs) have been associated with a lower incidence of cardiovascular events and sudden cardiac death. Flaxseed is one of the richest plant sources of Ω‐3 PUFAs and has been observed to retard the progression and accelerate the regression of atherosclerotic plaque. The aim of the study was to examine the effects of dietary flaxseed on heart function and arrhythmias that develop after a myocardial infarction (MI). The left anterior descending coronary artery was ligated in rats to induce the MI. Rats were randomized into five groups: sham MI with normal chow, MI with normal chow, MI with 10% milled flaxseed supplementation (flax), MI with 4.4% supplemented flax oil rich in alpha‐linolenic acid (ALA), and MI with flax lignan secoisolariciresinol diglucoside (SDG) supplementation (0.44%). Animals were fed with their respective diets for two weeks before and for 8 weeks after the surgery. Echocardiography and continuous ECG recordings were obtained after ligation to confirm the induction of the MI, to check for arrhythmias and to assess cardiac function. Histological examination was also performed to evaluate cardiac fibrosis. Dietary supplementation with flax, ALA, and SDG significantly reduced the incidence of arrhythmia. Hearts obtained from flax, ALA, and SDG supplemented animals exhibited the smallest infarct size (12.39±0.77%, 13.70±1.20%, 11.63±1.36% vs. 34.02±3.22%, p&lt;0.001). The left ventricle in the flax group was significantly less dilated compared to the control group (6.41±0.22 mm vs. 8.26±0.28 mm, p&lt;0.001). A significantly small percentage of myocardial fibrosis and levels of tumor necrosis factor‐α were observed in all flax groups compared to the MI group (p&lt;0.001). Together, this study generates evidence for a beneficial effect of flaxseed in patients post MI for the prevention of arrhythmias and ventricular remodeling.Support or Funding InformationThis work was supported by AAFC, CIHR, SaskFlax, Western Grain Research Foundation, Pizzey's Ingredients and St Boniface Hospital Foundation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Exposure to environmentally relevant concentration of second hand smoke increased blood pressure and decreased baroreflex sensitivity in mice

BACKGROUNDSecond hand smoke (SHS), a main indoor air pollution, is a significant risk factor for cardiovascular morbidity and mortality. Epidemiological studies link SHS exposure to increased sympathetic nerve activity (SNA) and blood pressure (BP), suggesting a central component in SHS‐induced cardiovascular dysregulation. However, we have limited information on effects of SHS on baroreflex sensitivity (BRS), an indicator of central regulation of BP and a stronger link to cardiovascular morbidity and mortality than the elevated BP. Additionally, we lack information on whether exposure to environmentally relevant levels of SHS affects BP regulation. Here we sought to test the hypothesis that chronic exposure to an environmentally relevant level of SHS elevates BP and reduces BRS.METHODSAdult male C57BL/6J mice (11 wk old) were implanted with BP/ECG telemetry devices. After two weeks of recovery from surgery, mice were randomly assigned to either filtered air (FA, n=18) or SHS (n=14) for up to 12 weeks. The SHS exposure level was similar to that of a smoky bar (3 mg/m3, 6 hr/d, 5 d/wk). 36 hours of continuous BP and ECG recordings were performed after the 5th day of exposure each week. Data were divided into three 12‐hr periods based on light cycle: dark 1, light and dark 2. Standard deviation of beat‐to‐beat BP was taken as the BP variability (BPV). BRS was determined with the sequence method using systolic BP.RESULTSThere was no difference in body weight between FA‐ and SHS‐exposed mice over the 12‐wk period. SHS exposure had no effect on dark‐light difference in BP, BPV, and BRS. Comparing to FA mice, SHS mice had higher systolic BP (~2.4 mmHg, p &lt; 0.05), mean BP (~3 mmHg, p &lt;0.05), and diastolic BP (~4 mmHg, p &lt; 0.05) by 4 weeks of exposure. SHS reduced pulse pressure (PP, ~2 mmHg, p &lt; 0.05), although the magnitude of the reduction diminished over time. In contrast, the SHS‐induced reduction in BRS was time dependent and accumulative, having a slower onset than changes in BP and PP, and becoming more severe with increasing exposure duration (−0.8%, −6.2%, and −12.3% for 4, 8, and 12 wk, respectively). SHS did not change BP variability, regardless of exposure duration.CONCLUSIONSThe effect of SHS on increased BP was observed after 4 wk of exposure and sustained through 12 wk of exposure. In contrast, SHS‐induced reductions in BRS showed a delayed onset that accumulates with prolonged exposures. The data suggest that SHS may activate multiple mechanisms resulting in BP dysregulation.Support or Funding InformationR01 ES025229This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The association between cardiac autonomic neuropathy and diabetes control.

Introduction: Cardiac autonomic neuropathy (CAN) is one of major complications of diabetes mellitus (DM) that increases the risk of cardiovascular disorders, abnormal ventricular depolarization with poor prognosis as well as increased mortality and morbidity. Indeed, CAN has close relation with blood glucose level in diabetic patients. We investigated the relation of CAN with diabetes control.Materials and methods: Totally, 115 diabetic patients (mean age 50.87±13.90 years old; 78 females) underwent study. All patients had DM and cardiac sinus rhythm. Nobody had sickness affecting cardiac rhythm and blood pressure. In addition, they did not take drugs that had effect on blood pressure, cardiac rhythm, and QT interval. Forty-six patients had tight and 69 patients had uncontrolled DM according to American Diabetes Association (ADA) criteria. The CAN was assessed based on heart rate variation during physical examination (at rest tachycardia and orthostatic hypotension) and standard Ewing’s tests (deep-breathing and laying-to-standing tests) with bedside continuous ECG recording. The P-value <0.05 is considered significant.Results: Seventy-five patients (65.2%) had CAN. In patients with CAN, 13.9% were symptomatic and 51.3% were asymptomatic. Resting tachycardia and hypotension were found in 5.2%, 8.7% of patients, respectively. Abnormal deep-breathing and laying-to-standing tests were found in 73% and 71.3% of asymptomatic patients, respectively. CAN was more prevalence at uncontrolled DM (67.3% vs 63.7%) but the difference was not significant. The prevalence of CAN had direct association with duration of DM in both tight and uncontrolled groups (P<0.05). The mean of age, sex, and type of treatment had no association with CAN prevalence.Conclusion: The prevalence of CAN, especially asymptomatic type, was high. Its prevalence was increased with prolonged duration of DM. But we did not find any relationship between CAN and glycemic control level.

Effect of beta-blockade on quantitative microvolt T-wave alternans in 24-hour continuous 12-lead ECG recordings in patients with long QT syndrome.

The aim of study was to investigate effects of beta-blockade on microvolt T-wave alternans (TWA), a precursor of lethal arrhythmia, in patients with long QT syndrome (LQTS). Eleven consecutive LQTS patients, types 1 (n=6), 3 (n=2), and "non-1, non-2, non-3" (n=3) were enrolled. All patients underwent 24-hr continuous 12-lead ECG monitoring before and after initiation of beta-blockade therapy. TWA was measured using the modified moving average method. Seven (63.6%) of the 11 patients studied were symptomatic, with history of cardiac arrest or documented Torsade de Pointes (TdP) in 4 and syncope in three patients. After a median follow-up of 34months, beta-blockade reduced the number of symptomatic patients to 1 with TdP (p<0.02), in whom TdP frequency decreased from 25 events/60months (0.42 event/month) to seven events/69months (0.1 event/month). In association with this reduction in symptoms, peak TWA decreased by 47% in the cohort after a median of eight months of beta-blockade therapy [from 95 (74-130) to 50 (39.5-64.5) µV, p=0.01]. All patients exhibited TWA ≥42µV before beta-blockade therapy, which eliminated these episodes in four patients. Daily frequency of TWA ≥42µV episodes decreased by 87% [from 15 (6-26) to 2 (0-5) episodes/day, p=0.009]. This study is limited by the small sample size and is mainly hypothesis generating. TWA monitoring deserves further evaluation as a risk marker and a guide to therapy in LQTS patients in future large-scale studies.

Usefulness of Short-Lasting Episodes of Supraventricular Arrhythmia (Micro-Atrial Fibrillation) as a Risk Factor for Atrial Fibrillation

According to the present European Society of Cardiology's guidelines for atrial fibrillation (AF), the definition of AF contains a 30-second time criterion, based on consensus. The aim of this cohort study is to evaluate whether very short-lasting episodes of AF, micro-AF, are risk factors for developing AF and to compare AF detection between continuous and intermittent ECG recordings applied in parallel. All participants, n = 102, were identified from the STROKESTOP study, a Swedish mass-screening study for AF. Participants were divided into 2 groups depending on results in the STROKESTOP study: a micro-AF group (with abrupt onset episodes of ≥4 consecutive supraventricular beats, irregular rate-to-rate intervals, absence of regular p waves, lasting for <30 seconds), n = 54, and a control group, n = 48. After a follow-up period participants who were clinically free of AF were invited to undergo repeat AF screening during a 2-week period, using continuous ECG recording and 30 seconds intermittent recordings simultaneously. After 2.3years of follow-up, significantly more participants in the micro-AF group had developed AF, 27 of 54 (50%), compared with the control group, 5 of 48 (10%), p < 0.001. Among the 94 participants not already diagnosed with AF who underwent AF-screening, 25 of 25 (100%) AF cases were detected with help of continuous monitoring whereas 10 of 25 (40%) AF cases were found with intermittent ECGs. In conclusion, micro-AF seems to be an important risk factor for the development of AF in an elderly population. The detection of AF was significantly higher using 2 weeks of continuous ECG monitoring compared with intermittent 30-second ECG recordings twice daily for 2 weeks.

An approach to 24-hour electrocardiogram monitoring in sheep experimental model

Sheep could be an excellent research subject for large animal experimental studies because of their heart structure and physiology have a lot similarity to the human. Long term ECG monitoring is a convenient tool for human and possibly veterinary clinical practice and research. Continuous ECG recording can be used to monitor and evaluate body physiological responses in various experimental conditions. Experience on sheep ECG monitoring techniques is sparse and mostly focused on short term ECG recordings. We developed a peculiar technique of 24-hour sheep ECG monitoring based on the available data on large mammal model, where we tried to share some insights and practical solutions working with this type of animals for ECG monitoring by using several commercially available ECG monitors also used for the human practice. Some producer specific hardware and software characteristic that we found important in daily practice were also discussed. In conclusion, sheep as big animal is relatively good object for Holter monitoring experimental studies: ECG monitoring is easily affordable, registered ECG signal is of similar quality as in human clinical practice, which is sufficient for the heart rhythm monitoring and arrhythmia and conduction disorder diagnostics. Additional effort might be needed for 24-hour heart rate variability calculations because manual revision of software ECG signal interpretations is requiring, but short-term calculations can be made easy.