Increase In QRS Duration Research Articles

Baseline Framingham risk score does not predict future ECG-derived QRS duration over an average of 3.3\xa0years

BackgroundProlonged electrocardiogram (ECG) QRS duration has been associated with increased cardiovascular risk. It is unclear whether the main predictor of cardiovascular risk, the Framingham risk score also predicts short-term changes in ECG QRS duration. Our aim is to determine whether baseline Framingham risk score is associated with baseline or changes in QRS duration.MethodsA retrospective cross-sectional analysis was performed using observational data obtained from two hundred two participants. Framingham risk score was calculated using an online risk calculator. QRS duration was obtained using a 10 s trace from a Welch Allyn PC-based 12-lead ECG system.ResultsAverage follow-up duration was 3.3 ± 1.1 years. Mean QRS change was 1.8 ± 11.4 ms. Specifically, among two hundred two participants, there are 104 subjects with a greater QRS duration at follow-up, while 98 subjects had the same or a shorter follow-up QRS duration. Baseline Framingham risk score did not significantly predict an increase in QRSd with an odds ratio of 1.04 (P = 0.230). Regression analysis of QRS duration at baseline and Framingham risk at baseline had a weak association (R2 = 0.020; P = 0.043). The Framingham risk score at follow-up was likewise has a weak association with follow-up QRS duration (R2 = 0.045; P = 0.002).ConclusionsOur results do not demonstrate a statistically significant association between Framingham risk parameters and future QRS duration changes over longitudinal time. QRS duration had variable changes between baseline and follow-up. This might suggest that a longer period of follow-up is required to document more stable increases in QRS duration associated with ventricular pathology. A larger population study is needed to confirm our observations.

Hypertrophic cardiomyopathy and left ventricular non compaction: Relationship between ventricular mass and shortened QRS duration

Sudden death is a public health issue and is related to malignant ventricular arrhythmias in 80%. Structural heart diseases may be involved, sometimes detected by ECG abnormalities. Increase in QRS duration is an accepted marker for arrhythmic events. However, consequences of decreased QRS durations are unknown. Some genetic cardiomyopathies may be associated with very narrow QRS. To determine the association between an increased left ventricular mass (LVM) in a population of sarcomeric hypertrophic cardiomyopathy (HCM) and left ventricular non compaction (LVNC) population and a shortened duration of ventricular depolarization. 4 groups were retrospectively formed: HCM, LVNC, post hypertensive Hypertrophy Left Ventricular (LVH) and controls. Indexed automatic LVM on MRI was correlated to automatic measurement of QRS duration on ECG. Potential confounding factors that can modify intraventricular conduction were collected. Our population includes 221 patients with HCM, 28 with LVNC, 16 patients with LVH and 40 controls. Median QRS duration was 92 ms (95% CI 81–96) for HCM, 104 ms (95% CI 82–124) for LVNC, 110 ms (95% CI 92–128) for LVH and 92 ms (95% CI 85–96) for controls ( P < 0.01). LVM was 100 g/m 2 (95% CI 80–115), 90 g/m 2 (95% CI 75–100), 108 g/m 2 (95% CI 78–123) and 68 g/m2 (95% CI 59–76) respectively ( P < 0,01). A negative correlation was found between LVM and QRS duration in the HCM group (rho = −0.22, P = 0.03). The relationship is the opposite in LVNC (rho = 0.46, P = 0.01), LVH (rho = 0.13, P = 0.62) and controls (rho = 0.35, P = 0.29). Multivariate analysis confirms this trend with significant results. QRS duration increases with LVM in the case of NCVG, HVG or without heart disease, while it decreases with increasing LVM in the case of HCM. This could reflect a more developed Purkinje network, with better electrical synchronization and faster ventricular activation. These results could be used as diagnostic criteria in the future.

The effects of transcatheter aortic valve implantation on cardiac electrical properties

IntroductionTranscatheter aortic valve implantation (TAVI) is associated with cardiac electrical disturbances. However, beyond the risks of pacemaker implantation, few studies have performed a detailed assessment of the effects of TAVI on several cardiac electrical properties. ObjectivesTo assess the frequency and type of electrocardiographic disturbances following TAVI, according to the type of prostheses and to assess predictors of these disturbances. MethodsWe performed a detailed retrospective analysis of all electrocardiograms in patients who underwent TAVI, before and after the procedure, at a tertiary center from August 2007 to October 2016. Patients with permanent pacemakers were excluded. ResultsWe included 182 patients (78±8 years; 56% female) and self-expanding prostheses (SEP) were implanted in 54%. Most patients (80%) were in sinus rhythm at baseline. After TAVI, 21% of patients developed new-onset atrial fibrillation and there was a significant increase in PR interval at discharge (186±41 ms vs. 176±32; p=0.003), which was not maintained after at six-month follow-up (181±35 ms, p=0.06). There was also a significant increase in QRS duration at discharge (129±28 ms vs. 114±25 at baseline p<0.0001), which persisted at six-months (122±28 ms, p<0.0001). New-onset left-bundle branch block (LBBB) was observed in 25% of patients. The depth of valve implantation was a predictor of new LBBB at discharge after multivariate analysis (OR 37.6, 95% CI 14.6–65.2, p=0.001). ConclusionsThe main electrocardiographic disturbances post TAVI were PR prolongation, increased QRS and new-onset LBBB. These disturbances were more pronounced in patients undergoing SEP implantation and tended to improve at six-month follow-up. The depth of valve implantation was a predictor of conduction disturbances.

Trait-associated noncoding variant regions affect TBX3 regulation and cardiac conduction.

Genome-wide association studies have implicated common genomic variants in the gene desert upstream of TBX3 in cardiac conduction velocity. Whether these noncoding variants affect expression of TBX3 or neighboring genes and how they affect cardiac conduction is not understood. Here, we use high-throughput STARR-seq to test the entire 1.3 Mb human and mouse TBX3 locus, including two cardiac conduction-associated variant regions, for regulatory function. We identified multiple accessible and functional regulatory DNA elements that harbor variants affecting their activity. Both variant regions drove gene expression in the cardiac conduction tissue in transgenic reporter mice. Genomic deletion from the mouse genome of one of the regions caused increased cardiac expression of only Tbx3, PR interval shortening and increased QRS duration. Combined, our findings address the mechanistic link between trait-associated variants in the gene desert, TBX3 regulation and cardiac conduction.

LOCALIZATION OF THE LEFT VENTRICULAR MYOCARDIAL SCARRING AND ITS ELECTRICAL ACTIVATION IN PATIENTS WITH HEART FAILURE AND DIFFERENT RESPONSE TO CARDIAC RESYNCHRONIZATION THERAPY

Introduction.As a significant number of patients with heart failure (HF) does not respond to cardiac resynchronization therapy (CRT), a lot of research has deservedly focused on optimization, and better patient selection. The ideal resynchronization depends on different factors, from device programming to heart features and left ventricle (LV) lead position. Analysis of the 12-lead electrocardiogram (ECG) is the most simple method which can provide important information on LV lead location, presence of scar at LV pacing site, and fusion of intrinsic activation or RV pacing with LV pacing.Purpose. To analyze the electrophysiological and structural heart features and their correlation with the ECG pattern during biventricular (BV) pacing in patients with HF and CRT devices.Methods. The study included 47 patients (mean age 62.3±8.9 years) with LBBB, QRS duration ≥ 130 ms, left ventricular ejection fraction (LVEF) ≤ 35%, heart failure (HF) NYHA II-IV despite optimal pharmacological therapy during months. All patients had undergone CRT-D implantation. Late-gadolinium enhancement-cardiovascular magnetic resonance (LGE-CMR), 12-lead ECG, non-invasive cardiac mapping (NICM) (with obtaining the zone of late LV activation (ZLA)) were undertaken prior to CRT devices implantation. NICM with cardiac CT and evaluation of LV lead position, ECG pattern during BV pacing (#1 - fusion complex with increased or dominant R wave, independent of QRS duration, #2- QS pattern with QRS duration normalization, and #3- QS pattern with increased QRS duration) were undertaken after CRT devices implantation. Response to CRT was estimated by echo and was defined as decrease in LV end-systolic volume by &gt; 15% after 6 months of follow-up.Results. CRT was effective in 28 patients (59.5%). According to the results of NICM, zone of late LV activation more often was located at 5,6,11,12 segments, and LV pacing site - at 6,7,12 segments of LV. In the “response” group overlap of scar zone and zone of late LV activation was observed (p=0.005). The presence of scar tissue in the LV pacing site was associated with CRT non-response (p&lt;0.001), and the pacing zone of late LV activation resulted in the best CRT response (p&lt;0.001). The distance from the LV electrode to the zone of late LV activation was less in the “CRT response” group (33 [20;42] mm vs 83 [55;100] mm, p&lt;0.001). The most beneficial ECG pattern during BV pacing was #2, and #3 was more often observed in the group “CRT non-response”; configuration #1 was intermediate between ECG patterns #2 and #3.Conclusions. A comprehensive examination, including the study of the structural and electrophysiological heart features is important for the optimal positioning the LV lead and subsequent CRT device programming. The simple analysis of the QRS pattern during BV pacing can show whether biventricular pacing is adequately performed and can reveal inadequate CRT programming and LV lead positioning.

Hypertrophic cardiomyopathy and left ventricular non compaction: Relationship between ventricular mass and shortened QRS duration

Structural heart disease may be involved in the occurrence of cardiac arrhythmias and sudden death. Increase in QRS duration is an accepted marker for arrhythmic events and SD. However, consequences of decreased QRS durations are unknown. Some genetic cardiomyopathies may be associated with very narrow QRS. To determine the association between an increased myocardial mass in a population of sarcomeric hypertrophic cardiomyopathy and left ventricular non compaction population and a shortened duration of ventricular depolarization. Patients with sarcomeric hypertrophic cardiomyopathy (HCM), left ventricular non compaction (LVNC), post hypertensive left ventricular hypertrophy (LVH) and controls with healthy heart were retrospectively included. Calculation of left ventricular mass (LVM) on MRI was correlated to automatic measurement of QRS duration on ECG. Potential confounding factors that can modify intraventricular conduction and ECG were collected. Preliminary analysis included 51 patients with HCM, 8 NCVG, 12 LVH and 39 controls. Median duration of QRS was 91 ms [IC 95% 84–99.5] in HCM, 85 ms [IC 95% 81–91] in LVNC, 97 ms [IC 95% 91–99.7] in LVH and 90 ms [IC 95% 85–96] in controls, P = 0.19. LVM was 81 g/m 2 [IC 95% 63–103], 97 g/m 2 [IC 95% 77–115], 76 g/m 2 [IC 95% 59–126] and 53 g/m 2 [IC 95% 39–59] respectively, P < 0.05. A negative non significant correlation was found between LVM and QRS duration in HCM (rho = − 0,15 P = 0.2) while a trend to reverse positive correlation was present in LVNC (rho = 0.5 P = 0.17), LVH (rho = 0.6 P = 0.03) and controls (rho = 0.26 P = 0.09). QRS duration increase with LVM in LVNC, LVH and controls while tending to decrease in HCM although non significantly. The myocardial thickness in this population may then be a reflection of a more developed Purkinje network, which is responsible for faster ventricular activation. When confirmed, these results may be used in the future for enhance diagnosis.

Changes in QRS Duration Are Associated with a Therapeutic Response to Sacubitril-valsartan in Heart Failure with Reduced Ejection Fraction.

BACKGROUNDRecent studies have demonstrated that angiotensin receptor neprilysin inhibitors (ARNIs) can reverse the cardiac remodeling effects that occur in heart failure with reduced ejection fraction (HFrEF). These studies have also suggested that ARNIs have favorable effects on ventricular dyssynchrony. We assessed the changes in QRS duration associated with ARNIs in patients with HFrEF.METHODSWe retrospectively investigated patients with HFrEF (defined by a left ventricular ejection fraction [LVEF] ≤ 35%) who were treated with ARNIs for at least six months. We divided the patients into QRS shortening and non-QRS shortening groups according to their electrocardiogram (ECG) findings. We also compared changes in echocardiographic parameters between the groups.RESULTSA total of 68 patients with HFrEF were included (mean age: 62.5 years, 74.6% male). Twenty-one patients had significant ischemic heart disease (IHD). Thirty-five patients exhibited QRS-duration shortening on follow-up ECGs (mean change: −7.8 msec), and 33 patients showed no changes or increased QRS duration (mean change: 5.1 msec). The QRS shortening group exhibited significant improvement in LVEF (12.5 ± 15.3% vs. 1.7 ± 9.5%; p < 0.001) when compared with the non-QRS shortening group. The QRS shortening group also had significantly lower LV end-diastolic dimension (LVEDD), LV end-systolic dimension (LVESD) and LV mass index (LVMI) than did the non-QRS shortening group. The change in QRS duration was significantly correlated with the change in LVEF (r = -0.329, p = 0.011) and LVESD (r = 0.298, p = 0.022).CONCLUSIONSAmong patients with HFrEF treated with ARNIs, the QRS shortening group showed favorable LV systolic function recovery, and reversal of cardiac remodeling compared to those of the non-QRS shortening group. Change in the QRS duration, which reflects LV synchrony, may be associated with response to ARNIs in patients with HFrEF.

Prevalence of mechanical dyssynchrony in heart failure patients according to QRS width

The aim of this study was to define the prevalence of mechanical (atrio-ventricular, interventricular and intraventricular) dyssynchrony in heart failure patients with different QRS durations. A total of 46 patients with heart failure (dilated cardiomyopathy with LVEF < 40%, NYHA II-IV) were prospectively evaluated using 12-lead electrocardiogram and complete echocardiographic examination including tissue Doppler imaging. All the patients had sinus rhythm and the dilated cardiomyopathy was primitive in 37% of patients and ischemic in the others. According to QRS duration, 16 patients had QRS ≥ 150 ms (group 1), 15 patients had QRS duration between 120 and 149 ms (group 2) and 15 patients had QRS duration < 120 ms (group 3). Interventricular dyssynchrony (IVD) was present in 62% of group 1, 13% of group 2 and was absent in group 3 ( P < 0,001). Intraventricular dyssynchrony (IntraVD) was present respectively in 94%, 40%, 20% of groups 1,2, and 3 ( P < 0,001). However, there was no significant difference in the prevalence of atrioventricular dyssynchrony (AVD) between the three groups. A multiparametric approach by focusing on criteria combination found that the association of IVD + IntraVD + AVD was present only in group 1 and the combination of two criteria was seen only in group 1 and 2 with a significantly higher prevalence in group 1 ( P < 0,01). The prevalence of mechanical dyssynchrony increases with the increasing QRS duration and the combination of criteria is significantly more prevalent when the QRS width is ≥ 150 ms. Intraventricular dyssynchrony can be observed in heart failure patients with a narrow QRS complex and may be useful in predicting left ventricular reverse remodelling after CRT. The lack of dyssynchrony in some patients with standard CRT indication by QRS duration may sometimes explain the non-responder's rates.

QRS duration is associated with all-cause mortality in type 2 diabetes: The diabetes heart study

BackgroundQRS-duration predicts mortality in patients with heart failure and, to a lesser extent, the general population. However, in patients with diabetes, its prognostic significance is unknown. To better understand how QRS-duration relates to mortality among those with diabetes, we explored survival as a function of QRS-duration in the Diabetes Heart Study. MethodsThe study population included 1335 participants. Cox proportional hazards modeling was used to evaluate the relationship between QRS-duration and all-cause mortality, comparing those with QRS-duration ≤120 vs. >120 (ms). Multivariable models adjusted for age, sex, race, hypertension, smoking, years with diabetes, BMI, systolic blood pressure, cholesterol, triglycerides, glomerular filtration rate, and hemoglobin A1c. Results and conclusionsParticipants were: mean age 61 ± 9, 55% women, 83% white; 99 participants (7.5%) had a QRS-duration >120. After 11,000 person-years of follow-up (median 8.5 years; maximum 13.9 years), 266 participants had died (20%). Participants with baseline QRS-duration >120 had an adjusted hazard ratio for all-cause mortality of 1.56 (95% CI 1.05–2.24; p = 0.027). Modeling QRS-duration as a continuous variable, we found an 11% increase in all-cause mortality for each 10 ms increase in QRS-duration. In conclusion, QRS-duration is associated with subsequent all-cause mortality among those with type 2 diabetes—participants with QRS-duration >120 ms had a 56% increase in all-cause mortality, even after adjustment for conventional risk factors. Given the ubiquitous presence of ECG data in the medical record, QRS-duration may prove to be a useful prognostic measure, especially among those with diabetes.

Direct and Indirect Suppression of Scn5a Gene Expression Mediates Cardiac Na+ Channel Inhibition by Wnt Signalling

BackgroundMyocardial infarction and heart failure are associated with reduced voltage-gated Na+ current (INa) that promotes arrhythmias and sudden deaths. We have previously shown that the Wnt/β-catenin signalling (Wnt signalling), which is active in heart disease, reduces cardiac INa, suggesting that Wnt signalling may be a potential therapeutic target. However, because Wnt signalling is required for the homeostasis of many noncardiac tissues, administration of Wnt inhibitors to heart patients would cause significant side effects. The present study aims to elucidate the molecular mechanisms of cardiac INa inhibition by Wnt, which would identify cardiac-specific therapeutic targets. MethodsWnt signalling was activated in neonatal rat ventricular myocytes by Wnt3a protein. Adenovirus expressing Wnt3a was injected into the adult rat ventricle. CRISPR/Cas9 and chromatin immunoprecipitation were used for mechanistic studies. ResultsWnt signalling activation in neonatal rat ventricular myocytes reduced Nav1.5 protein and Scn5a mRNA, but increased Tbx3, a known suppressor of Scn5a. Chromatin immunoprecipitation showed that Wnt signalling inhibits Scn5a expression through downstream mediator (TCF4) binding to both Tbx3 and Scn5a promoters. Overexpression or knockdown of Tbx3 directly modified Nav1.5 and INa, whereas CRISPR/Cas9-induced mutations at TCF4 binding sites within the Scn5a promoter attenuated Wnt inhibition of Scn5a and Nav1.5. In adult rat hearts, adenovirus expressing Wnt3a reduced Nav1.5, increased QRS duration in electrocardiogram, and increased the susceptibility to ventricular tachycardia. ConclusionsWnt signalling inhibits the Na+ channel by direct and indirect (via Tbx3) suppression of Scn5a transcription. Strategies to block TCF4 binding to the Tbx3 and Scn5a promoters would represent novel strategies for cardiac-specific inhibition of the Wnt pathway to rescue INa and prevent sudden cardiac deaths.

P3802Electrophysiological and structural heart features in patients with heart failure and response to cardiac resynchronization therapy

Abstract Introduction As a significant number of patients with heart failure (HF) does not respond to cardiac resynchronization therapy (CRT), a lot of research has deservedly focused on optimization, and better patient selection. The ideal resynchronization depends on different factors, from device programming to heart features and left ventricle (LV) lead position. Analysis of the 12 lead electrocardiogram (ECG) is the most simple method which can provide important information on LV lead location, presence of scar at LV pacing site, and fusion of intrinsic activation or RV pacing with LV pacing. Purpose To analyze the electrophysiological and structural heart features and their correlation with the ECG pattern during biventricular (BV) pacing in patients with HF and CRT devices. Methods The study included 47 patients (mean age 62,3±8,9 yrs) with LBBB, QRS≥130 ms, LV ejection fraction (LVEF) ≤35%, heart failure (HF) NYHA II-IV despite optimal pharmacological therapy during 3 months. All patients had undergone CRT-D implantation. Late-gadolinium enhancement-cardiovascular magnetic resonance, 12 lead ECG, non-invasive cardiac mapping (NICM) (with obtaining the zone of late LV activation were undertaken prior to CRT devices implantation. NICM with cardiac CT and evaluation of LV lead position, ECG pattern during BV pacing (#1 - fusion complex with increased or dominant R wave, independent of QRS duration, #2- QS pattern with QRS duration normalization, and #3- QS pattern with increased QRS duration) were undertaken after CRT devices implantation. Response to CRT was estimated by echo and was defined as decrease in LV end-systolic volume by &gt;15% after 6 months of follow-up. Results CRT was effective in 28 patients (59,5%). According to the results of NICM, zone of late LV activation more often was located at 5,6,11,12 segments, and LV pacing site – at 6,7,12 segments of LV. In the “response” group overlap of scar zone and zone of late LV activation was observed (p=0,005). The presence of scar tissue in the LV pacing site was associated with CRT non-response (p&lt;0.001), and the pacing zone of late LV activation resulted in the best CRT response (p&lt;0.001). The distance from the LV electrode to the zone of late LV activation was less in the “CRT response” group (33 [20; 42] mm vs 83 [55; 100] mm, p&lt;0.001). The most beneficial ECG pattern during BV pacing was #2, which found more often found in case of pacing zone of late LV activation. Configuration #3 was more often observed in the group “CRT non-response”; #1 was intermediate between ECG patterns #2 and #3. Conclusions A comprehensive examination, including the study of the structural and electrophysiological heart features is important for the optimal positioning the LV lead and subsequent CRT device programming. The simple analysis of the QRS pattern during BV pacing can show whether biventricular pacing is adequately performed and can reveal inadequate CRT programming and LV lead positioning.

Relation of Increasing QRS Duration Over Time and Cardiovascular Events in Outpatients With Heart Failure

An increase in the duration of the QRS complex over time has been shown to be associated with poor clinical outcomes in specific subgroups of heart failure (HF) patients. There is a paucity of data on the clinical impact of increasing QRS duration on outcomes in HF with narrow QRS duration. This was a retrospective study of consecutive adult referrals to a tertiary outpatient HF clinic over a 2-year period. All patients with a narrow QRS, (<130 ms) were included. The primary outcome was mortality. Secondary outcomes were HF hospitalization and a composite of HF hospitalization, implantation of cardiac resynchronization therapy or left ventricular assist device and cardiac transplant. A total of 253 patients with 2 or more QRS measurments were included. Death occurred in 41 patients (16%), 258 HF hospitalizations occurred in 116 patients (46%) and the composite occurred in 127 patients (50%). Multivariable analyses found that a rate of QRS duration change of ≥1 ms/month was independently associated with increased mortality (odds ratio [OR] 2.26, 95% confidence interval [CI] 1.04 to 4.91), HF hospitalization (relative risk [RR] 2.01, 95% CI 1.37 to 2.94), and the composite (OR 2.40, 95%CI 1.44 to 4.02). A new QRS >130 ms was also independently associated with mortality (OR 3.27, 95%CI 1.29-8.32), HF hospitalization (RR 2.75, 95% CI 1.72 to 4.4) and the composite (OR 2.52, 95%CI 1.27 to 4.99). In conclusion, in patients with HF and a narrow baseline QRS, an increase in QRS duration of ≥1 ms per month is associated with increased mortality and HF hospitalization. HF patients may benefit from serial monitoring of QRS duration.

Cardiac manifestations and prognostic implications of hereditary transthyretin amyloidosis associated with transthyretin Ala97Ser

The cardiac manifestations of late-onset hereditary transthyretin amyloidosis with p.A97S variant have not been extensively studied, and the prognostic factors remain unclear. The clinical profile, echocardiography, and ECG of patients diagnosed with ATTR p.A97S polyneuropathy between 2000 and 2016 were retrospectively collected. 67 patients with ATTR p.A97S were collected. A total of 82% of patients met the criteria for left ventricular (LV) hypertrophy. Reduced global longitudinal strain (GLS) was noted in 42.1% of patients, and 14% of patients had a relative apical sparing pattern. A low voltage pattern in the ECG was observed in 31.3% of patients, while 64.2% presented with a pseudoinfarction pattern. End-systolic LV inner dimension (HR: 2.25 (95% CI: 1.01-5.01), p=0.048), reduced GLS (HR: 5.26 (1.08-25.0), p=0.039), relative apical longitudinal strain (RALS>1, HR: 8.57 (1.69-43.3), p=0.009), increased E/A ratio (HR: 6.51 (1.17-36.4), p=0.033), and increased QRS duration (HR: 1.02 (1.00-1.04), p=0.05) were correlated with reduced survival in univariate analysis. Multivariate analysis revealed reduced RALS was significantly correlated with reduced survival (HR: 13.00 (1.81-93.45), p=0.011). Our findings reveal that ATTR p.A97S is a cardiomyopathy as well as a polyneuropathic syndrome. Routine use of more contemporary echocardiographic techniques are recommended to identify cardiac amyloidosis and provide prognostic information.

Ventricular Dyssynchrony is Associated with Worse Left Ventricular Ejection Fraction Trajectories in Severe Decompensated Systolic Heart Failure

Introduction Increased QRS duration (QRSd) and left ventricular dyssynchrony are associated with worse outcomes in heart failure (HF). The implication of QRSd on left ventricular ejection fraction (LVEF) trajectories among patients with severe decompensated systolic HF is unclear. Methods Patients hospitalized with HF between 2014-2018 with an LVEF ≤ 35% and at least two echocardiograms with LVEF assessments were included. Patients received guideline-directed medical and device therapies. Survival was assessed for up to 4 years after the index admission. LVEF trajectory was defined as the difference between the lowest LVEF and the highest LVEF, multiplied by -1 if the lowest LVEF was more recent than the highest LVEF. Linear regression was used to evaluate the association between LVEF trajectory and QRSd, and logistic regression was used to assess survival based on QRSd and LVEF trajectory. Results Among 1,674 patients (65.3 ± 14.2 years, 35.9 % female), 39% had QRSD > 120 ms. The lowest LVEF was 26.7% ± 9.7%, the highest LVEF was 45.5% ± 14.5%, and the LVEF trajectory had a median of 5% with an interquartile range of -10% to +25%. The frequency of QRSd less than 120 ms, 120-149 ms, and greater than or equal to 150 ms were 60.5%, 20.5%, and 19.5% respectively. Increasing QRSd was associated with more negative LVEF trajectories (r = -0.24, p Conclusions Increasing QRS duration in HF is associated with worsening LVEF trajectories and increased mortality despite contemporary guideline-directed medical and device therapy. The effect of QRS duration on survival appears to be mediated both by its impact on LVEF trajectory and mechanisms independent of the LVEF trajectory.

Melatonin attenuates bisphenol A‐induced alterations in the cardio‐renal system of rats through the antioxidant defense mechanism

Bisphenol A (BPA), an endocrine disrupting chemical (EDC) used in the production of plastics and epoxy resins has been incriminated in a number of biological dysfunctions while melatonin (MLT) is a known antioxidant capable of ameliorating EDC‐induced perturbations. Although limited number of studies exist on the effect of BPA on the cardio‐renal system, there is the dearth of research information on the effect of MLT on rats exposed to environmentally relevant doses of BPA. This study was therefore designed to investigate the effects of MLT on BPA‐induced alterations in the cardio‐renal system of rats. Gravid rats were randomly assigned into five groups (n=5): Group 1 (control) received 0.2 mL 1% dimethyl sulfoxide (DMSO)/99% canola oil as vehicle; Group 2 received BPA at 25 μg/kg/day; Group 3 received BPA at 250 μg/kg/day; Group 4 received BPA at 25 μg/kg/day with concurrent MLT 1 mg/kg/day; and Group 5 received BPA at 250 μg/kg/day with concurrent MLT 1 mg/kg/day. All treatments were administered by gavage from gestational day (GD) 10–21. Thereafter, three male offspring randomly from each litter per group (n=15) were weighed; blood pressure parameters and electrocardiogram taken on post‐natal day (PND) 120. The heart and kidney samples were harvested for markers of oxidative stress and antioxidant defense system, histopathology and histochemistry using standard methods. BPA induced a significant increase in heart rate but significantly decrease systolic, diastolic and mean arterial blood pressure. Exposure to BPA caused significant decrease in P wave interval, PR duration, R wave amplitude and QT interval but significant increase in QRS duration. Also, BPA significantly elevated both cardiac and renal MDA, H2O2, GSH and GPx. Cardiac and renal lesions induced by BPA included erosion of epithelial cells, congestion of blood vessels as well as necrosis. Moreover, BPA induced a significant reduction in cardiac and renal polysaccharide activities. However, the concomitant treatment with MLT attenuated all the observed BPA‐induced alterations of the cardio‐renal system. Hence, MLT attenuates alterations induced by environmentally relevant doses of BPA in the cardio‐renal system.Support or Funding InformationNoneThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of diurnal variations in the QRS complex and T waves on the eligibility for subcutaneous implantable cardioverter-defibrillators

Subcutaneous implantable cardioverter-defibrillators (S-ICDs) are an established therapy for preventing sudden cardiac death. However, a considerable number of patients still undergo inappropriate shocks even after conventional preimplantation electrocardiographic (ECG) screening. This study aimed to elucidate the additional effect of diurnal variations in the QRS complex and T waves of 24-hour Holter screening on S-ICD eligibility. Patients with transvenous ICDs who did not need pacing were selected for the study. The ECG was recorded by placing the electrodes to simulate the 3 sensing vectors of the S-ICD, with the patient in the standing and supine positions (conventional), during exercise, and during 24-hour Holter screening. We investigated the additional discrimination of diurnal variations in patients ineligible for S-ICDs as well as characteristics of those patients. Of the 86 patients (82% men; mean age 54±16 years) analyzed by all 3 screenings, 2 (2.3%) and 3 (3.4%) were considered ineligible by conventional and exercise screening, respectively.An additional 21 patients (24.4%) were found ineligible through Holter screening. A multivariate logistic regression analysis demonstrated that Brugada syndrome and an increased QRS duration per millisecond were associated with ineligibility (odds ratio 5.74; 95% confidence interval 1.74-20.2; P = .003 and odds ratio 1.04; 95% confidence interval 1.01-1.07; P = .007, respectively). T-wave oversensing was mostly observed during 0-6 AM, but no significant diurnal variations were observed in the incorrect QRS profiles. The detection of diurnal variations through Holter monitoring in addition to conventional screening is expected to be useful for determining S-ICD eligibility.

Assessment of anthracycline-induced long-term cardiotoxicity in patients with hematological malignancies

BACKGROUND: Anthracyclines are antibiotic antineoplastic drugs used in the treatment of various hematological and solid malignancies. They are well-known for their cardiotoxic side effects which are related to their cumulative dosages. Many investigations are used to detect such cardiotoxicity, the gold standard of which is the endomyocardial biopsy that has a limited use because it is an invasive procedure. The aims of this study were to explore the cardiotoxicity induced by anthracyclines in patients with hematological malignancies by using electrocardiography (ECG) and echocardiography and to determine relationship between the detected changes in ECG and echocardiography, with some demographic and clinical variables. PATIENTS AND METHODS: A cross-sectional study of fifty patients was recruited at Al-Imamein Al-Kadhemein Medical City from March 2014 to January 2015. ECG and echocardiography were done to the patients to study several parameters such as ejection fraction (EF), diastolic dysfunction, QRS voltage, QRS duration, and corrected QT (QTc) both at baseline and reassessment. Reassessment was done after completing induction for leukemia patients and at mid-term reassessment for lymphoma patients. RESULTS: ECG showed reduction in QRS voltage, increase in QRS duration, and increase in QTc, all of which showed statistical significance and may reflect the effect on the depolarization and repolarization on the myocardium. The echo study showed the development of systolic left ventricular (LV) dysfunction (EF 30% from baseline) with the development of LV dysfunction was also found. CONCLUSIONS: Significant changes in QRS voltage, QRS duration, QTc, as well as the occurrence of LV systolic dysfunction and diastolic dysfunction were noted. The mean cumulative dose at which LV systolic dysfunction occurred was about 250 mg/m2.

MOLECULAR STUDY OF FMD INFECTED EGYPTIAN BUFFALO CALVES WITH REFERENCE TO ELECTROCARDIOGRAPHY AND CARDIAC BIOMARKERS AS PROGNOSTIC TOOLS

A total of 200 Egyptian buffalo calves aging between 9-11 months previously vaccinated with local trivalent oil inactivated vaccine (O, A and SAT-2), in different locations at Menufyia Governorate showing typical clinical signs of FMD were examined for molecular characterization of FMD virus, electrocardiographic picture (ECG) and cardiac biomarkers. The results of serological tests revealed that incidence of non-structural proteins against natural infection with FMDV was 31.5% in serum samples collected from vaccinated buffalo calves. Moreover, 51.5 % of the samples showed detection of structural proteins against trivalent vaccination. On the other hand, there were no protective antibodies against FMDV in 17 % of the examined samples. ECG of FMD infected calves showed ventricular premature depolarization with flattening of P- wave and increased QRS duration with decrease in its amplitude compared with healthy calves. In FMD infected buffalo calves, there were significant (P < 0.01) increases in (cTnI), (CK-MB), urea, CL and K and there was significant (P < 0.01) decrease in Na levels than that of healthy ones. The identified strains in FMD infected Egyptian buffalo calves were unique and different from the vaccinal and other Egyptian strains as well as they were clustered with Topotype ME-SA. Cardiac enzymes along with ECG can be used as useful prognostic tools in FMD infected Egyptian buffalo calves.

TCT-477 Prevalence and Clinical Impact of Baseline QRS Duration in Patients With Severe Aortic Stenosis Two Years After Aortic Valve Replacement in the PARTNER II Trial

Increasing QRS duration on 12-lead electrocardiogram (ECG) is associated with mortality and adverse outcomes in patients with cardiomyopathy, but its clinical impact in patients with severe aortic valve stenosis (AS) treated with transcatheter (TAVR) or surgical (SAVR) valve replacement is unknown

Electrophysiological Consequences of Congenital Heart Defects Shaped by Primary Cilia‐Dependent Cardiac Developmental Processes

Congenital heart defects (CHD) affect approximately 8 out of every 1,000 newborns, resulting in the birth of 35,000 babies with CHD annually in the United States. Primary cilia are small, finger‐like structures that extend from almost all eukaryotic cells and have been found to play a pivotal role in both development and maturation of embryonic and perinatal heart. Our laboratory presents a novel cardiac phenotype resulting from the elimination of primary cilia from cardiac neural crest cells (cNCC) of the embryonic mouse heart. This phenotype combines a high incidence of outflow tract defects, including double‐outlet right ventricle, with severe damage to the membranous interventricular septum, non‐compaction of the developing ventricular myocardium, and perinatal lethality. The purpose of this ongoing project is to develop a reliable method for obtaining electrocardiograms (ECG) in perinatal mice, to perform a comprehensive and diagnostic analysis of the combined anatomical and physiological data and to better understand the perinatal lethality resulting from primary cilia elimination. A Cre recombinase‐expressing mouse (Wnt1:Cre) was crossed with the Ift88flox/flox mouse, resulting in elimination of primary cilia from cNCC during mid embryonic heart development. Extensive histological and imaging analyses were previously performed to characterize and reconstruct the anatomical abnormalities. Perinatal electrocardiography (ECG) was then performed on 34 pups within the first day of life (P1), where mice remained conscious in the prone position. Modified gel‐coated ECG electrodes were placed in the right axilla of the left lower quadrant of the abdomen, allowing for a two‐lead electrophysiological evaluation. ECGs were collected for a total of 5 minutes, after which, pups were euthanized for further histological evaluation. ECG analysis included heart rate (HR; minimum, maximum and mean), QRS duration, P wave presence, PR interval, and overall ECG interpretation. Mutant mice (n=26) demonstrated a significantly lower HR when compared to littermate wildtype (WT) (n=8) mice (233±24 beats per minute (bpm) vs 30±2 bpm, p&lt;0.0001). QRS duration was significantly lengthened in the mutant mice compared with WT (0.020±0.001 milliseconds (ms) vs 0.014±0.001 ms, p=0.018). P wave activity was absent in 54% of mutant mice when compared to 100% appearance in WT mice. Combined incidence of bradycardia, HR irregularity and the absence of P wave activity seen in the mutant mice suggests that the QRS complexes demonstrated were not sinus in nature, rather of a junctional or ventricular origin. Whether this is due to a defect in SA node development, communication between the atria and ventricles, or hypoxia is currently under investigation. Increased QRS duration seen in mutant mice is suggestive of additional depolarization abnormalities. Collectively, these results characterize a relationship between the anatomical phenotype resulting from primary cilia elimination and abnormal embryological development of cardiac electrical conduction pathways.Support or Funding InformationGenerous support for this project was made possible by the Saving tiny Hearts Foundation and the Peter Morgane Fellowship Program at the University of New England.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.