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Aims: The randomized, double‐blind, placebo‐controlled HOPE‐HF trial assessed the benefit of atrio‐ventricular (AV) delay optimization delivered using His bundle pacing. It recruited patients with left ventricular ejection fraction ≤40%, PR interval ≥200 ms, and baseline QRS ≤140 ms or right bundle branch block. Overall, there was no significant increase in peak oxygen uptake (VO2max) but there was significant improvement in heart failure specific quality of life. In this pre‐specified secondary analysis, we evaluated the impact of baseline PR interval, echocardiographic E‐A fusion, and the magnitude of acute high‐precision haemodynamic response to pacing, on outcomes. Methods and results: All 167 randomized participants underwent measurement of PR interval, acute haemodynamic response at optimized AV delay, and assessment of presence of E‐A fusion. We tested the impact of these baseline parameters using a Bayesian ordinal model on VO2max, quality of life and activity measures. There was strong evidence of a beneficial interaction between the baseline acute haemodynamic response and the blinded benefit of pacing for VO2 (Pr 99.9%), Minnesota Living With Heart Failure (MLWHF) (Pr 99.8%), MLWHF physical limitation score (Pr 98.9%), EQ‐5D visual analogue scale (Pr 99.6%), and exercise time (Pr 99.4%). The baseline PR interval and the presence of baseline E‐A fusion did not have this reliable ability to predict the clinical benefit of pacing over placebo across multiple endpoints. Conclusions: In the HOPE‐HF trial, the acute haemodynamic response to pacing reliably identified patients who obtained clinical benefit. Patients with a long PR interval (≥200 ms) and left ventricular impairment who obtained acute haemodynamic improvement with AV‐optimized His bundle pacing were likely to obtain clinical benefit, consistent across multiple endpoints. Importantly, this gradation can be reliably tested for before randomization, but does require high‐precision AV‐optimized haemodynamic assessment to be performed. [ABSTRACT FROM AUTHOR]

Background: The use of left bundle branch area pacing (LBBAP) for bradycardia pacing and cardiac resynchronization is increasing, but implants are not always successful. We prospectively studied consecutive patients to determine whether septal scar contributes to implant failure. Methods: Patients scheduled for bradycardia pacing or cardiac resynchronization therapy were prospectively enrolled. Recruited patients underwent preprocedural scar assessment by cardiac MRI with late gadolinium enhancement imaging. LBBAP was attempted using a lumenless lead (Medtronic 3830) via a transeptal approach. Results: Thirty‐five patients were recruited: 29 male, mean age 68 years, 10 ischemic, and 16 non‐ischemic cardiomyopathy. Pacing indication was bradycardia in 26% and cardiac resynchronization in 74%. The lead was successfully deployed to the left ventricular septum in 30/35 (86%) and unsuccessful in the remaining 5/35 (14%). Septal late gadolinium enhancement was significantly less extensive in patients where left septal lead deployment was successful, compared those where it was unsuccessful (median 8%, IQR 2%–18% vs. median 54%, IQR 53%–57%, p <.001). Conclusions: The presence of septal scar appears to make it more challenging to deploy a lead to the left ventricular septum via the transeptal route. Additional implant tools or alternative approaches may be required in patients with extensive septal scar. [ABSTRACT FROM AUTHOR]

Aims: Excessive prolongation of PR interval impairs coupling of AV contraction, which reduces left ventricular pre-load and stroke volume, and worsens symptoms. His-bundle pacing allows AV-delay shortening while maintaining normal ventricular activation. HOPE-HF evaluated whether AV-optimized His pacing is preferable to no-pacing, in double-blind cross-over fashion, in patients with heart failure, left ventricular ejection fraction (LVEF) ≤40%, PR interval ≥200ms and either QRS ≤140ms or right BBB.Methods and Results: Patients had atrial and His-bundle leads implanted (and an ICD lead if clinically indicated) and were randomized, to 6-months of pacing and 6-months of no-pacing utilizing a cross-over design. The primary outcome was peak oxygen uptake during symptom-limited exercise. Quality of life, LVEF and patients' holistic symptomatic preference between arms were secondary outcomes. 167 patients were randomized: 90% men, 69±10 years, QRS duration 124±26ms, PR interval 249±59ms, LVEF 33±9%. Neither peak VO2 (+0.25 ml/min/kg, 95% CI -0.23 to +0.73, p=0.3) nor LVEF (+0.5%, 95% CI -0.7 to 1.6, p=0.4) changed with pacing but Minnesota Living with Heart Failure quality of life improved significantly (-3.7, 95% CI -7.1 to -0.3, p=0.03). 76% of patients preferred His-bundle pacing-on and 24% pacing-off (p<0.0001).Conclusion: His-bundle pacing did not increase peak oxygen uptake but, under double-blind conditions, significantly improved quality of life and was symptomatically preferred by the clear majority of patients. Ventricular pacing delivered via the His bundle did not adversely impact ventricular function during the 6 months. This article is protected by copyright. All rights reserved. [ABSTRACT FROM AUTHOR]

Background: The risk factors for developing pacing induced left ventricular dysfunction (LVD) in patients with high burden of right ventricular pacing (RVP) is poorly understood. Therefore, in the present study, we aimed to assess the determinants of pacing induced LVD. Methods: Our data were retrospectively collected from 146 patients with RVP > 40% who underwent generator change (GC) or cardiac resynchronization therapy (CRT) upgrade between 2016 and 2019 who had left ventricular ejection fraction (EF) ≥50% at initial implant. Results: A total of 75 patients had CRT upgrade due to pacing induced LVD (EF < 50%) and 71 patients with preserved LV function (EF ≥ 50%) had a GC. Primary indication for pacing in both groups was complete heart block. Male predominance (p =.008), prior myocardial infarction (MI) (p =.001), atrial fibrillation (AF) (p =.009), chronic kidney disease (CKD) (p =.005), and borderline low systolic function (BLSF) (EF 50%–55%) (p =.04) were more prevalent in the CRT upgrade group. Presence of AF (odds ratio [OR] = 3.05, 95% confidence interval [CI] 1.42–6.58; p =.004), BLSF (OR = 3.8, 95% CI 1.22–11.8; p =.02), and male gender (OR = 2.41, 95% CI 1.14–5.08; p =.02) were independent predictors for RVP induced LVD. Age (OR = 1.08, 95% CI 1.02–1.14; p =.005) and BLSF (OR = 5.33, 95% CI 1.26–22.5; p =.023) were independent predictors of earlier development of LVD after implant. Conclusions: Our results suggested that AF, BLSF, and male gender are predictors for development of pacing induced LVD in patients with high RVP burden. LVD can occur at any time after pacemaker implant with BLSF and increasing age associated with earlier development of LVD. [ABSTRACT FROM AUTHOR]

Background: Permanent pacemaker (PPM) implantation is a common complication of transcatheter aortic valve implantation (TAVI). The optimum timing of PPM implantation is still unclear as conduction abnormalities evolve and a balance needs to be struck between conservative delays in the hope of conduction recovery and overutilization of pacing. This study aimed to assess the safety and efficacy of early PPM implantation, without an observation period, among TAVI patients. Methods: This is a retrospective, observational study of 1398 TAVI patients. Clinical and pacing data were collected at baseline, 30 days and at a median of 15 (4–21) months post‐TAVI. Study endpoints included PPM‐related complications, pacing utilization and hospital length of stay. Results: One hundred five patients (8.2%) required a PPM, of which 13 were implanted pre and 92 post‐TAVI. Seventy‐six percent required pacing for either second‐ or third‐degree heart block. Time to implantation for post‐TAVI PPM was 1 (0–3) day. Six patients experienced a pacing‐related complication‐ lead displacement (n = 3), hematoma (n = 2), and device infection (n = 1). Pacing utilization defined as pacing >10% of the time or a pacing requirement at the time of the pacing check was demonstrated in 83% of patients. Multivariate analysis revealed complete heart block (CHB) was the only independent predictor of pacing utilization. Hospital length of stay for the post‐TAVI PPM group was longer than the group without PPM (4 [2–8] vs. 3 [2–4] days; p <.001). Conclusions: Early PPM implantation in TAVI patients is safe and majority of patients require pacing in the short and mid‐term. [ABSTRACT FROM AUTHOR]

Background: His bundle pacing (HBP) is an alternative to biventricular pacing (BVP) for delivering cardiac resynchronization therapy (CRT) in patients with heart failure and left bundle branch block (LBBB). It is not known whether ventricular activation times and patterns achieved by HBP are equivalent to intact conduction systems and not all patients with LBBB are resynchronized by HBP. Objective: To compare activation times and patterns of His‐CRT with BVP‐CRT, LBBB and intact conduction systems. Methods: In patients with LBBB, noninvasive epicardial mapping (ECG imaging) was performed during BVP and temporary HBP. Intrinsic activation was mapped in all subjects. Left ventricular activation times (LVAT) were measured and epicardial propagation mapping (EPM) was performed, to visualize epicardial wavefronts. Normal activation pattern and a normal LVAT range were determined from normal subjects. Results: Forty‐five patients were included, 24 with LBBB and LV impairment, and 21 with normal 12‐lead ECG and LV function. In 87.5% of patients with LBBB, His‐CRT successfully shortened LVAT by ≥10 ms. In 33.3%, His‐CRT resulted in complete ventricular resynchronization, with activation times and patterns indistinguishable from normal subjects. EPM identified propagation discontinuity artifacts in 83% of patients with LBBB. This was the best predictor of whether successful resynchronization was achieved by HBP (logarithmic odds ratio, 2.19; 95% confidence interval, 0.07–4.31; p =.04). Conclusion: Noninvasive electrocardiographic mapping appears to identify patients whose LBBB can be resynchronized by HBP. In contrast to BVP, His‐CRT may deliver the maximum potential ventricular resynchronization, returning activation times, and patterns to those seen in normal hearts. [ABSTRACT FROM AUTHOR]

His‐Purkinje conduction system pacing (HPCSP) in the form of His bundle pacing (HBP) and left bundle branch pacing (LBBP) allows normal left ventricular activation, thereby preventing the adverse consequences of right ventricular pacing. HBP has been established for several years with centers from China, Europe, and North America reporting their experience. There is international guidance as to how to implant such systems with the differing patterns of His bundle capture clearly described. LBBP is a more recent innovation with potential advantages including improved pacing parameters. HPCSP has been extensively studied in a variety of indications including cardiac resynchronization therapy, atrioventricular node ablation, and bradycardia pacing. This review will focus on the clinical outcomes of HPCSP including mortality and morbidity of heart failure hospitalization and symptoms. [ABSTRACT FROM AUTHOR]

Aims: There is an important need for better biomarkers to predict left ventricular (LV) remodelling in dilated cardiomyopathy (DCM). We undertook a comprehensive assessment of cardiac structure and myocardial composition to determine predictors of remodelling.Methods and Results: Prospective study of patients with recent-onset DCM with cardiovascular magnetic resonance (CMR) assessment of ventricular structure and function, extracellular volume (T1 mapping), myocardial strain, myocardial scar (late gadolinium enhancement) and contractile reserve (dobutamine stress). Regression analyses were used to evaluate predictors of change in LV ejection fraction (LVEF) over 12 months. We evaluated 56 participants (34 DCM patients, median LVEF 43%; 22 controls). Absolute LV contractile reserve predicted change in LVEF (1% increase associated with 0.4% increase in LVEF at 12 months, P = 0.02). Baseline myocardial strain (P = 0.39 global longitudinal strain), interstitial myocardial fibrosis (P = 0.41), replacement myocardial fibrosis (P = 0.25), and right ventricular contractile reserve (P = 0.17) were not associated with LV reverse remodelling. There was a poor correlation between contractile reserve and either LV extracellular volume fraction (r = -0.22, P = 0.23) or baseline LVEF (r = 0.07, P = 0.62). Men were more likely to experience adverse LV remodelling (P = 0.01) but age (P = 0.88) and disease-modifying heart failure medication (beta-blocker, P = 0.28; angiotensin-converting enzyme inhibitor, P = 0.92) did not predict follow-up LVEF.Conclusions: Substantial recovery of LV function occurs within 12 months in most patients with recent-onset DCM. Women had the greatest improvement in LVEF. A low LV contractile reserve measured by dobutamine stress CMR appears to identify patients whose LVEF is less likely to recover. [ABSTRACT FROM AUTHOR]

An 85‐year‐old male was admitted to our center with a non‐ST elevation myocardial infarction. The patient had a dual‐chamber pacemaker in situ with an atrial and His lead. A transient increase in His threshold and loss of nonselective capture occurred at the presentation of right coronary artery infarction, peaking during rotational atherectomy therapy causing loss of capture and complete atrioventricular block. A follow‐up interrogation, 2 weeks postrevascularization, showed a return to a normal nonselective capture morphology and threshold measurements. Physicians should be aware of this complication in patients with His leads, particularly those with a history of coronary artery disease. [ABSTRACT FROM AUTHOR]

Background. Bone marrow necrosis (BMN) is a rare entity which presents with bone pain, fever, and peripheral cytopenia. Acute lymphoblastic leukaemia (ALL) is characterized by malignant proliferation of immature lymphocytes, and patients usually present with fatigue and bleeding manifestations. Presentation with BMN is an extremely rare finding and only few cases had been reported in the literature. Case Presentation. A 22-year-old male presented with nocturnal lower back ache, pleuritic central chest pain, and fever for two weeks. He was extensively investigated for a cause. His investigations revealed pancytopenia with severe neutropenia. Initial bone marrow aspiration and biopsy did not provide a positive result due to extensive necrosis. However, immunohistochemical analysis of few immature lymphoid cells on repeated BM biopsy showed evidence of acute lymphoblastic leukaemia. Conclusions. ALL usually presents with fatigue and bleeding manifestations. Presentation with BMN is extremely rare. The diagnosis was extremely challenging as this patient had only occasional atypical cells in the peripheral blood film and the repeat bone marrow (BM) biopsy showed extensive necrosis. [ABSTRACT FROM AUTHOR]

Abstract: Aims: In patients with heart failure and a pathologically prolonged PR interval, left ventricular (LV) filling can be improved by shortening atrioventricular delay using His‐bundle pacing. His‐bundle pacing delivers physiological ventricular activation and has been shown to improve acute haemodynamic function in this group of patients. In the HOPE‐HF (His Optimized Pacing Evaluated for Heart Failure) trial, we are investigating whether these acute haemodynamic improvements translate into improvements in exercise capacity and heart failure symptoms. Methods and results: This multicentre, double‐blind, randomized, crossover study aims to randomize 160 patients with PR prolongation (≥200 ms), LV impairment (EF ≤ 40%), and either narrow QRS (≤140 ms) or right bundle branch block. All patients receive a cardiac device with leads positioned in the right atrium and the His bundle. Eligible patients also receive a defibrillator lead. Those not eligible for implantable cardioverter defibrillator have a backup pacing lead positioned in an LV branch of the coronary sinus. Patients are allocated in random order to 6 months of (i) haemodynamically optimized dual chamber His‐bundle pacing and (ii) backup pacing only, using the non‐His ventricular lead. The primary endpoint is change in exercise capacity assessed by peak oxygen uptake. Secondary endpoints include change in ejection fraction, quality of life scores, B‐type natriuretic peptide, daily patient activity levels, and safety and feasibility assessments of His‐bundle pacing. Conclusions: Hope‐HF aims to determine whether correcting PR prolongation in patients with heart failure and narrow QRS or right bundle branch block using haemodynamically optimized dual chamber His‐bundle pacing improves exercise capacity and symptoms. We aim to complete recruitment by the end of 2018 and report in 2020. [ABSTRACT FROM AUTHOR]

Finite difference time domain (FDTD) method is a very poplar way of numerically solving partial differential equations. FDTD has a low operational intensity so that the performances in CPUs and GPUs are often restricted by the memory bandwidth. Recently, deeply pipelined FPGA accelerators have shown a lot of success by exploiting streaming data flows in FDTD computation. In spite of this success, many FPGA accelerators are not suitable for real-world applications that contain complex boundary conditions. Boundary conditions break the regularity of the data flow, so that the performances are significantly reduced. This paper proposes an FPGA accelerator that computes commonly used absorbing and periodic boundary conditions in many 3D FDTD applications. Accelerator is designed using a “C-like” programming language called OpenCL (open computing language). As a result, the proposed accelerator can be customized easily by changing the software code. According to the experimental results, we achieved over 3.3 times and 1.5 times higher processing speed compared to the CPUs and GPUs, respectively. Moreover, the proposed accelerator is more than 14 times faster compared to the recently proposed FPGA accelerators that are capable of handling complex boundary conditions. [ABSTRACT FROM AUTHOR]

Heart Failure (HF) is a common disorder associated with substantial morbidity and mortality. beta adrenergic receptors (betaAR) are the primary pathway through which cardiac function is influenced. Chronic beta(1)AR activation is implicated in the pathogenesis of HF and betaAR blockade improves survival in left ventricular systolic dysfunction. Common functional polymorphisms in beta adrenergic receptor genes (ADRB) have been associated with HF phenotypes, and with pharmacogenetic interaction with beta adrenergic receptor blockers (beta blockers). However, these associations have not been consistently replicated. The evidence for ADRB variant involvement in pathogenesis, progression and response to beta blockers in HF is reviewed. In addition, a meta-analysis of three studies analysing the effect of ADRB1 Arg389Gly polymorphism on left ventricular remodelling with the use of beta blockers, demonstrating a 5% improvement in left ventricular ejection fraction in Arg389 homozygotes, is presented. There is now accumulating molecular evidence for a different functional response to beta blockers associated with this polymorphism. In the future, confirmed genotypic associations may enable patients to be identified who are either at greater risk of developing HF, whose HF may rapidly progress, or who are unlikely to benefit from beta blockers, and such patients may benefit from targeted aggressive therapy. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma and the most common oral pre-malignancies appear to be related to the habit of betel-quid chewing in Sri Lanka. Although hypermethylation of the tumour suppressor genes in oral cancer have been well documented, little information has been available concerning hypermethylation in oral pre-cancerous lesions. In the present study, we investigated the hypermethylation of p14, p15 and p16 in pre-cancerous lesions including epithelial dysplasia and submucous fibrosis. Methods: All samples were obtained from patients with a betel-quid chewing habit in Sri Lanka. Sixty-four patients were clinically diagnosed with leukoplakia, and histopathologically diagnosed with mild or severe dysplasia. Ten patients were diagnosed with submucous fibrosis without epithelial dysplasia. CpG island hypermethylation was assessed by a methylation-specific PCR method. Immunohistochemical staining was performed using anti-p53 antibodies. Results: A high frequency of hypermethylation of p14, p15 and p16 was detected in the pre-cancerous lesions, although no hypermethylation was found in normal epithelium. The frequency of hypermethylation was higher than that of positive staining for p53 mutation except in the case of p16 in mild dysplasia. No significant correlation was observed between p53-positive reactions and hypermethylation in any lesions. The hypermethylation was highly detectable even in p53-negative lesions, suggesting that hypermethylation of p14, p15 and p16 occur regardless of whether the lesions have p53 mutations or not. Conclusions: The present study indicates that hypermethylation may be involved in the pathogenesis of oral pre-cancerous lesions associated with betel-quid chewing in Sri Lanka. [ABSTRACT FROM AUTHOR]

Abstract: Heart Failure (HF) is a common disorder associated with substantial morbidity and mortality. β adrenergic receptors (βAR) are the primary pathway through which cardiac function is influenced. Chronic β1AR activation is implicated in the pathogenesis of HF and βAR blockade improves survival in left ventricular systolic dysfunction. Common functional polymorphisms in β adrenergic receptor genes (ADRB) have been associated with HF phenotypes, and with pharmacogenetic interaction with β adrenergic receptor blockers (β blockers). However, these associations have not been consistently replicated. The evidence for ADRB variant involvement in pathogenesis, progression and response to β blockers in HF is reviewed. In addition, a meta-analysis of three studies analysing the effect of ADRB1 Arg389Gly polymorphism on left ventricular remodelling with the use of β blockers, demonstrating a 5% improvement in left ventricular ejection fraction in Arg389 homozygotes, is presented. There is now accumulating molecular evidence for a different functional response to β blockers associated with this polymorphism. In the future, confirmed genotypic associations may enable patients to be identified who are either at greater risk of developing HF, whose HF may rapidly progress, or who are unlikely to benefit from β blockers, and such patients may benefit from targeted aggressive therapy. [Copyright &y& Elsevier]

The article presents a case study of a 53-year-old man with history of anterior myocardial infarction and undergone a secondary prevention dual-chamber implantable cardioverter defibrillator (ICD; with an apical right ventricular lead). The ICD was programmed with a paced atrioventricular (AV) delay of 190 milliseconds (MS) and sensed AV delay of 170 ms. He developed worsening dyspnea over the next few days and an electrocardiogram (ECG) was performed.