Whole genome sequencing of families diagnosed with cardiac channelopathies reveals structural variants missed by whole exome sequencing.

Cardiac channelopathies are a group of heritable disorders that affect the heart's electrical activity due to genetic variations present in genes coding for ion channels. With the advent of new sequencing technologies, molecular diagnosis of these disorders in patients has paved the way for early identification, therapeutic management and family screening. The objective of this retrospective study was to understand the efficacy of whole-genome sequencing in diagnosing patients with suspected cardiac channelopathies who were reported negative after whole exome sequencing and analysis. We employed a 3-tier analysis approach to identify nonsynonymous variations and loss-of-function variations missed by exome sequencing, and structural variations that are better resolved only by sequencing whole genomes. By performing whole genome sequencing and analyzing 25 exome-negative cardiac channelopathy patients, we identified 3 pathogenic variations. These include a heterozygous likely pathogenic nonsynonymous variation, CACNA1C:NM_000719:exon19:c.C2570G:p. P857R, which causes autosomal dominant long QT syndrome in the absence of Timothy syndrome, a heterozygous loss-of-function variation CASQ2:NM_001232.4:c.420+2T>C classified as pathogenic, and a 9.2 kb structural variation that spans exon 2 of the KCNQ1 gene, which is likely to cause Jervell-Lange-Nielssen syndrome. In addition, we also identified a loss-of-function variation and 16 structural variations of unknown significance (VUS). Further studies are required to elucidate the role of these identified VUS in gene regulation and decipher the underlying genetic and molecular mechanisms of these disorders. Our present study serves as a pilot for understanding the utility of WGS over clinical exomes in diagnosing cardiac channelopathy disorders.

A large-scale targeted proteomics of serum and tissue shows the utility of classifying high grade and low grade meningioma tumors.

BACKGROUND: Meningiomas are the most prevalent primary brain tumors. Due to their increasing burden on healthcare, meningiomas have become a pivot of translational research globally. Despite many studies in the field of discovery proteomics, the identification of grade-specific markers for meningioma is still a paradox and requires thorough investigation. The potential of the reported markers in different studies needs further verification in large and independent sample cohorts to identify the best set of markers with a better clinical perspective. METHODS: A total of 53 fresh frozen tumor tissue and 51 serum samples were acquired from meningioma patients respectively along with healthy controls, to validate the prospect of reported differentially expressed proteins and claimed markers of Meningioma mined from numerous manuscripts and knowledgebases. A small subset of Glioma/Glioblastoma samples were also included to investigate inter-tumor segregation. Furthermore, a simple Machine Learning (ML) based analysis was performed to evaluate the classification accuracy of the list of proteins. RESULTS: A list of 15 proteins from tissue and 12 proteins from serum were found to be the best segregator using a feature selection-based machine learning strategy with an accuracy of around 80% in predicting low grade (WHO grade I) and high grade (WHO grade II and WHO grade III) meningiomas. In addition, the discriminant analysis could also unveil the complexity of meningioma grading from a segregation pattern, which leads to the understanding of transition phases between the grades. CONCLUSIONS: The identified list of validated markers could play an instrumental role in the classification of meningioma as well as provide novel clinical perspectives in regard to prognosis and therapeutic targets.

1029 genomes of self-declared healthy individuals from India reveal prevalent and clinically relevant cardiac ion channelopathy variants.

BACKGROUND: The prevalence and genetic spectrum of cardiac channelopathies exhibit population-specific differences. We aimed to understand the spectrum of cardiac channelopathy-associated variations in India, which is characterised by a genetically diverse population and is largely understudied in the context of these disorders. RESULTS: We utilised the IndiGenomes dataset comprising 1029 whole genomes from self-declared healthy individuals as a template to filter variants in 36 genes known to cause cardiac channelopathies. Our analysis revealed 186,782 variants, of which we filtered 470 variants that were identified as possibly pathogenic (440 nonsynonymous, 30 high-confidence predicted loss of function ). About 26% (124 out of 470) of these variants were unique to the Indian population as they were not reported in the global population datasets and published literature. Classification of 470 variants by ACMG/AMP guidelines unveiled 13 pathogenic/likely pathogenic (P/LP) variants mapping to 19 out of the 1029 individuals. Further query of 53 probands in an independent cohort of cardiac channelopathy, using exome sequencing, revealed the presence of 3 out of the 13 P/LP variants. The identification of p.G179Sfs*62, p.R823W and c.420 + 2 T > C variants in KCNQ1, KCNH2 and CASQ2 genes, respectively, validate the significance of the P/LP variants in the context of clinical applicability as well as for large-scale population analysis. CONCLUSION: A compendium of ACMG/AMP classified cardiac channelopathy variants in 1029 self-declared healthy Indian population was created. A conservative genotypic prevalence was estimated to be 0.9-1.8% which poses a huge public health burden for a country with large population size like India. In the majority of cases, these disorders are manageable and the risk of sudden cardiac death can be alleviated by appropriate lifestyle modifications as well as treatment regimens/clinical interventions. Clinical utility of the obtained variants was demonstrated using a cardiac channelopathy patient cohort. Our study emphasises the need for large-scale population screening to identify at-risk individuals and take preventive measures. However, we suggest cautious clinical interpretation to be exercised by taking other cardiac channelopathy risk factors into account.

Early repolarization syndrome, epilepsy, and atrial fibrillation in a young girl with novel KCND3 mutation managed with quinidine.

A 6-year-old girl presented with a difficult to control epilepsy syndrome. On evaluation, additional presyncope episodes associated with polymorphic ventricular tachycardia were also noted. A diagnosis of early repolarization syndrome (ERS) was made with an early repolarization pattern on electrocardiogram, documented VT episodes, and clinical presyncope (proposed Shanghai score 7). Paroxysmal atrial fibrillation (AF) was also noted on 24-h Holter recordings. The child was stabilized with isoprenaline infusion and was later discharged with arrhythmia control on quinidine and cilostazol. The genetic evaluation revealed a potassium channel KCND3 gene missense mutation. The case highlights the association of epilepsy syndrome and AF with ERS; the possible association of KCND3 gene mutation with a malignant phenotype; and management issues in a small child.

Dynamics and vector correlations of vacuum ultraviolet (VUV) photodissociation of CO2 at 155 nm.

In this work, the CO2 Vacuum Ultraviolet (VUV) photodissociation dynamics of the dominant O(1D) channel near 155 nm have been studied using Velocity Map Imaging (VMI) technique. Correlations among the transition dipole moment of the parent molecule, recoil velocity vector and rotational angular momentum vector of the photofragments were extracted from the anisotropic angular distributions of the images. The vector correlations extracted indicated a picture of photodissociation mainly via the excited 21A' (A) state. The transition dipole moment  lies in the bending molecular plane, and the j⃑ is pointing perpendicular to the plane, while the µ-v vectors angle is between 41°-45°. In addition, a clear trend was observed. As the product CO rotational state j increases, the spatial anisotropy parameter (ß ≡ 2ß20(20)) decreases. This j-dependent attenuation of spatial anisotropy parameter can be explained mainly with the consideration of non-axial recoil effect. These results are in good agreement with both theoretical work and previous experimental work.

Restless legs syndrome/Willis-Ekbom disease among patients with resistant hypertension versus stroke patients-a prospective study.

BACKGROUND: Epidemiological studies have shown an increased prevalence and incidence of hypertension as well as a higher incidence of stroke among patients suffering from RLS. The objective of this study was to estimate the prevalence of RLS among patients with resistant hypertension (RH) and compare the clinical characteristics of these patients with patients of stroke pre-existing RLS and with patients with primary RLS presenting to the Sleep clinic. METHODS: Consecutive patients with RH (without any identifiable cause on extensive work up) and consecutive in-patients with stroke were enrolled over a 3-year-period. Patients with RH fulfilling revised-IRLSSG-criteria for RLS comprised group 1 and those with stroke and RLS formed group 2. These were compared with patients diagnosed to have idiopathic RLS (iRLS) (Group 3). Prevalence of RLS in groups 1 and 2 and RLS characteristics in all groups were compared. RESULTS: Sixteen out of 56 RH patients (29%) formed group 1 and 43 out 346 of stroke patients (12%) formed group 2, while 43 consecutive iRLS patients were included in group 3. Age was significantly higher, with male dominance in group 2. Median age at symptom onset was significantly lower in group 1. Positive family history was similar in RH and iRLS patients and was significantly less common in stroke patients. Asymmetrical/unilateral distribution of symptoms was significantly more common in stroke group, compared to RH and iRLS groups. CONCLUSION: This study demonstrated a high prevalence of RLS among patients with resistant hypertension. RLS characteristics are different from those in patients with stroke, and very similar to primary RLS.

Bicuspid aortic valve and anomalous origin of the right ventricular branch in a patient with congenitally corrected transposition of great arteries: A rare association.

We hereby present a case of congenitally corrected transposition of great arteries association of bicuspid aortic valve morphology and anomalous separate origin of the right ventricular branch of the right coronary artery. We aim to highlight the role of computed tomography angiography in identifying these rare associations.

Effect of electron-phonon coupling on the transport properties of monolayers of ZrS2, BiI3 and PbI2: a thermoelectric perspective.

Thermoelectric materials are used for the conversion of waste heat to electrical energy. The transport coefficients that determine their thermoelectric properties depend on the band structure and the relaxation time of the charge carriers. Both of these are significantly affected by electron-phonon coupling. In this work, using a combination of density functional theory and semiclassical Boltzmann transport theory, we have studied the effect of electron-phonon coupling in monolayers of ZrS2, BiI3 and PbI2. Our results show that in these ionic materials charge carriers are primarily scattered by the optical modes that strongly couple with them. From our study it is conclusively shown that neglecting the contributions of optical modes to electron-phonon coupling in these low-dimensional ionic solids, as is usually done in the computation of relaxation time from deformation theory, results in severe overestimation of the relaxation time. In particular, neglecting the scattering of the optical phonons results in about two orders of magnitude overestimation of relaxation times in these materials. Moreover, we also find that the renormalization of the band structure not only results in the reduction of band gaps but also changes the band dispersion, which strongly affect different transport properties like the electrical conductivity and Seebeck coefficient. Amongst these three materials, we observe that carrier relaxation time due to electron-phonon scattering is reduced as the ionicity of the material decreases.

Metabolic effects of duodenojejunal bypass surgery in a rat model of type 1 diabetes.

BACKGROUND: Metabolic surgery has beneficial metabolic effects, including remission of type 2 diabetes. We hypothesized that duodenojejunal bypass (DJB) surgery can protect against development of type 1 diabetes (T1D) by enhancing regulation of cellular and molecular pathways that control glucose homeostasis. METHODS: BBDP/Wor rats, which are prone to develop spontaneous autoimmune T1D, underwent loop DJB (n = 15) or sham (n = 15) surgery at a median age of 41 days, before development of diabetes. At T1D diagnosis, a subcutaneous insulin pellet was implanted, oral glucose tolerance test was performed 21 days later, and tissues were collected 25 days after onset of T1D. Pancreas and liver tissues were assessed by histology and RT-qPCR. Fecal microbiota composition was analyzed by 16S V4 sequencing. RESULTS: Postoperatively, DJB rats weighed less than sham rats (287.8 vs 329.9 g, P = 0.04). In both groups, 14 of 15 rats developed T1D, at similar age of onset (87 days in DJB vs 81 days in sham, P = 0.17). There was no difference in oral glucose tolerance, fasting and stimulated plasma insulin and c-peptide levels, and immunohistochemical analysis of insulin-positive cells in the pancreas. DJB rats needed 1.3 ± 0.4 insulin implants vs 1.9 ± 0.5 in sham rats (P = 0.002). Fasting and glucose stimulated glucagon-like peptide 1 (GLP-1) secretion was elevated after DJB surgery. DJB rats had reduced markers of metabolic stress in liver. After DJB, the fecal microbiome changed significantly, including increases in Akkermansia and Ruminococcus, while the changes were minimal in sham rats. CONCLUSION: DJB does not protect against autoimmune T1D in BBDP/Wor rats, but reduces the need for exogenous insulin and facilitates other metabolic benefits including weight loss, increased GLP-1 secretion, reduced hepatic stress, and altered gut microbiome.

Exploring knowledge, attitude and practice regarding yoga among patients attending cardiology and neurology clinics in a tertiary care hospital in northern India.

Background The use of complementary and alternative medicine, particularly yoga is increasing in non-communicable diseases (NCDs). We assessed the overall awareness regarding yoga among patients and their opinion about it as an adjunct therapy for NCDs. Methods We included 384 patients attending the cardiology and neurology clinics at a tertiary care centre in northern India. A questionnaire was developed to assess the knowledge, attitude and practice of yoga as a therapy. Results Ninety per cent of patients were aware of yoga, mainly through print and electronic media. Of the surveyed patients, 22% practised yoga. Lack of time and knowledge were cited as the main reasons for non-practice among the non-practising patients (88%), of which 82% believed that yoga could be practised along with modern medicine. In addition, 61% were ready to accept treatment if offered at the surveyed tertiary care centre. Conclusions Adequate knowledge, awareness and attitude towards yoga appears to be present in contrast to the low practice among the patient population surveyed. If implemented in an integrated fashion, the patients were willing to accept yoga as an adjunct therapy for their cardiac and neurological disorders-an encouraging sign given the burden of NCDs in India.

Aneurysmal and obstructive lesions of the left ventricular outflow: evaluation on multidetector computed tomography angiography.

The left ventricular outflow is an anatomically complex region situated between the anterior leaflet of the mitral valve and the left ventricular aspect of the muscular and membranous interventricular septum. It gives rise to the aorta, provides support to the aortic valvular cusps, and houses important components of the conduction system. The left ventricular outflow handles high pressures and pressure variations and is subsequently affected by a variety of aetio-pathological conditions. Diseases involving the left ventricular outflow can be intraluminal, mural, or extramural, and the consequent complications of the lesions can be local, loco-regional, or even systemic. Appropriate evaluation requires comprehensive multimodality imaging with each modality contributing to assessment of different aspects of diagnosis, lesion characterization, local extension, prognostication for systemic complications and mortality, and the decision for the approach and type of intervention and aggressive follow-up in case non-interventional management is decided. In this review, we briefly describe the relevant anatomy and the gamut of structural abnormalities pertaining to the left ventricular outflow on multidetector computed tomography angiography.

Comparative Effectiveness of Targeted Intrathecal Drug Delivery Using a Combination of Bupivacaine with Either Low-Dose Fentanyl or Hydromorphone in Chronic Back Pain Patients with Lumbar Postlaminectomy Syndrome.

OBJECTIVE: Targeted intrathecal drug delivery (TIDD) is an effective interventional pain management modality often used in postlaminectomy patients with refractory chronic low back pain. A combination of intrathecal bupivacaine with an opioid is often used. However, intrathecal catheter tip granulomas have occurred with use of morphine or hydromorphone but generally not with fentanyl. The objective of this study was to compare the efficacy of TIDD using bupivacaine/fentanyl vs bupivacaine/hydromorphone in patients with chronic intractable low back pain postlaminectomy. MATERIALS AND METHODS: A retrospective comparative analysis of consecutive patients with lumbar postlaminectomy syndrome who were trialed and later received TIDD with a combination of bupivacaine/hydromorphone or bupivacaine/fentanyl between June 2009 and May 2016 at a single tertiary medical center. RESULTS: We identified a cohort of 58 lumbar postlaminectomy patients receiving a TIDD admixture of either hydromorphone/bupivacaine (30 patients) or low-dose fentanyl/bupivacaine (28 patients) with at least two years of follow-up. The fentanyl group had significantly lower baseline opioid consumption and a lower rate of intrathecal opioid dose escalation. Both groups had similar and significant reductions in pain scores over the two-year follow-up period. No granulomas were observed. CONCLUSION: TIDD using a low-dose fentanyl admixture with bupivacaine in patients with postlaminectomy syndrome and refractory chronic low back pain results in similar pain relief to TIDD with hydromorphone and bupivacaine. Low-dose intrathecal fentanyl leads to a lower rate of opioid escalation and may be safer than hydromorphone.

Bariatric surgery in patients with interstitial lung disease.

BACKGROUND: Perioperative pulmonary complications are frequent in patients with interstitial lung diseases (ILD). Limited literature exists regarding the safety of bariatric procedures in patients with ILD. This study aims to assess the safety, feasibility, and outcomes of patients with ILD who underwent bariatric surgery at our institution. METHODS: After IRB approval, all patients with preoperative diagnosis of ILD who had bariatric surgery at an academic center between 2004 and 2014 were retrospectively reviewed. RESULTS: A total of 25 patients with ILD underwent bariatric surgery: Roux-en-Y gastric bypass (n = 17, 68%), sleeve gastrectomy (n = 7, 28%), and adjustable gastric banding (n = 1, 4%). Twenty-one patients (84%) were females. The median age and preoperative body mass index (BMI) were 53 (IQR 42-58) years and 39 (IQR 37-44) kg/m2, respectively. The median operative time and length of stay was 137 (IQR 110-187) min and 3 (IQR 2-5) days, respectively. The 30-day complications were reported in four patients (16%) but there was no pulmonary complication or unplanned admission to the intensive care unit. At 1-year follow-up (85%), the median BMI and excess weight loss were 30 (IQR 25-36) kg/m2 and 67% (IQR 45-100), respectively. Compared to preoperative values, there was significant improvement in the pulmonary function test (PFT) variables at 1 year with respect to forced vital capacity (62% vs 74%; n = 13, p = 0.003), and diffusing capacity of the lungs for carbon monoxide (53% vs 66%; n = 10, p = 0.003). Six out of the seven potential lung transplant candidates became eligible for transplantation after weight loss, and one of them had successful lung transplant at 88 months after bariatric surgery. CONCLUSION: In our experience, bariatric patients with ILD achieved significant weight loss and improvement in PFT. Bariatric surgery in these higher risk ILD patients appears relatively safe with acceptable perioperative morbidity and improved candidacy for lung transplantation.

Coronary Artery Disease in Patients with Ischemic Stroke and TIA.

BACKGROUND AND OBJECTIVES: Ischemic stroke (IS) and coronary artery disease (CAD) share common risk factors and one may be the harbinger of the other. We aimed to study prevalence of symptomatic and asymptomatic CAD in a cohort of consecutive patients with IS and assess its relationship with intracranial and extracranial large artery cerebrovascular disease (LAD). METHODS: All consecutive eligible IS and Transient Ischemic Attack (TIA) patients were recruited into the study. Both clinically suspected and asymptomatic patients (N = 259) underwent myocardial Stress-rest Gated Technetium-99m (Tc99m) MIBI Myocardial Perfusion SPECT scan performed on a dual head SPECT-CT to estimate evidence of myocardial ischemia. RESULTS: Three hundred patients completed the study. Forty one patients were previously diagnosed cases of definitive CAD. Twelve patients were clinically suspected to have CAD and 247 patients were asymptomatic. Among these, 12 patients (4.81%) had a positive SPECT. The overall prevalence of CAD was 17.67% (n = 53). Presence of diabetes was an independent predictor of CAD (OR 1.98, 95% CI 1.07-3.67. P .02). No significant association was found between the presence of LAD and CAD in all subgroup comparisons. However, there was a suggestion of higher LAD among patients with known CAD compared with others. CONCLUSIONS: CAD is prevalent in patients with ischemic stroke. No definitive relationship was found between CAD and intracranial or extracranial LAD. Population based stratification tools are needed to further assess the need to detect subclinical CAD in patients with stroke.

No time, no money, no luck: Barriers to prenatal care among dalit women in rural Nepal.

In Nepal, a large gap exists between non-dalit and dalit women in regard to maternal mortality and prenatal care. Especially rural Dalits are far behind non-dalits in utilizing prenatal care. We explored rural dalit women's prenatal practices and barriers to accessing prenatal care. Interviews revealed that lack of cultural and economic capital, unequal domestic and economic burden, and gender and caste discrimination impact the use of prenatal care. The use of prenatal care might be improved by informing women about free services and incentives, better access and transportation, and heightened sensitivity to the situation of these women.

A curious case of impossible coronary sinus cannulation.

A 40-year-old male, diagnosed to have WPW syndrome and symptomatic with recurrent palpitations, was taken up for radiofrequency ablation. There was difficulty in coronary sinus cannulation. Coronary venogram revealed coronary sinus atresia with persistent left superior vena cava, and collateral venous pathways draining into the right atrium. This case is discussed for the rare coronary venous anomaly, its embryology and the difficulties in the management during electrophysiological studies.

Surgical management of gastroesophageal reflux disease in patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis (scleroderma) is frequently associated with both gastroesophageal reflux disease (GERD) and simultaneous esophageal dysmotility. Anti-reflux procedures in this patient population must account for the existing physiology of each patient and likely disease progression. We aim to compare perioperative and intermediate outcomes of fundoplication versus gastric bypass for the treatment of GERD. METHODS: After IRB approval, patients with systemic sclerosis undergoing fundoplication or gastric bypass for the treatment of GERD from 2004 to 2016 were identified. Demographics, perioperative data, immediate complications, and symptom improvement were retrieved and analyzed. RESULTS: Fourteen patients with systemic sclerosis underwent surgical treatment of GERD during the defined study period. Average body mass index was 26 kg/m2. Seven fundoplications (2 Nissens, 4 Toupets, and 1 Dor) and 7 Roux-en-Y gastric bypasses (RYGB) were performed. No 30-day mortality was observed in either group. Median follow-up was 97 months for the fundoplication group (range 28-204 months), and 19 months for the RYGB group (range 1-164 months). Preoperatively, dysphagia, heartburn, and regurgitation were present in 71% (n = 10), 86% (n = 12), and 64% (n = 9) of patients, respectively. Eleven patients had pH study prior to surgical intervention, and 91% of them had abnormal acid exposure. Esophagitis was evident in 85% (n = 11) of patients during preoperative upper endoscopy, and two patients had Barrett's esophagus. Impaired esophageal motility was present in all RYGB patients and 71% of fundoplication patients. Of the patients who had assessment of their GERD symptoms at follow-up, all five patients in the RYGB group and only 3 (50%) patients in the fundoplication group reported symptom improvement or resolution. CONCLUSIONS: Laparoscopic RYGB as an anti-reflux procedure is safe and may provide an alternative to fundoplication in the treatment of GERD for systemic sclerosis patients with esophageal dysmotility.

Comparison of laparoscopic jejunostomy tube to percutaneous endoscopic gastrostomy tube with jejunal extension: long-term durability and nutritional outcomes.

INTRODUCTION: Enteral access through the jejunum is indicated when patients cannot tolerate oral intake or gastric feeding. While multiple approaches for feeding jejunal access exist, few studies have compared the efficacy of these techniques. The purpose of this study was to investigate the long-term durability, re-intervention rates, and nutritional outcomes following percutaneous endoscopic gastrostomy tubes with jejunal extension tubes (PEG-JET) versus laparoscopic jejunostomy tubes (j-tubes). METHODS: Retrospective chart review was performed on all patients who underwent PEG-JET or laparoscopic jejunostomy tube placement from January 2005 through December 2015 at our institution. Thirty-day and long-term outcomes were compared between the two groups. RESULTS: A total of 105 patients underwent PEG-JET and 307 patients underwent laparoscopic j-tube placement during the defined study period. In terms of 30-day outcomes, patients who underwent PEG-JET placement were significantly more likely to experience a tube dislodgement event (p = 0.005) and undergo a re-intervention (p < 0.001). Patients who had a laparoscopic j-tube placed were significantly more likely to meet their enteral feeding goals (p = 0.002) and less likely to require nutritional supplementation with total parenteral nutrition (TPN) (p < 0.001). With regard to long-term outcomes, patients who underwent PEG-JET placement were significantly more likely to experience tube occlusion (p < 0.001) and require an endoscopic or surgical tube re-intervention (p < 0.001). Patients who underwent laparoscopic j-tube placement were significantly more likely to experience a tube site leak (p = 0.015) but were less likely to require nutritional supplementation with TPN (p = 0.001). CONCLUSION: Laparoscopic jejunostomy tubes provide more durable long-term enteral access compared to PEG-JET. Consideration should be given to laparoscopic jejunostomy tube placement in eligible patients who cannot tolerate oral intake or gastric enteral feeding.

Correlation of pacing site in right ventricle with paced QRS complex duration.

BACKGROUND: Pacing from RV mid septum and outflow tract septum has been proposed as a more physiological site of pacing and narrower paced QRS complex duration. The paced QRS morphology and duration in different RV pacing sites is under continued discussion. Hence, this study was designed to address the correlation of pacing sites in right ventricle with paced QRS complex duration. METHODS: Two hundred fifty-two consecutive patients who underwent pacemaker implantation were enrolled. Baseline clinical characteristics were recorded for each patient. All patient underwent fluoroscopy, electrocardiogram and echocardiography post pacemaker implantation. Paced QRS duration was calculated from the leads with maximum QRS duration. RESULTS: Mean paced QRS (pQRS) duration was significantly higher in apical septum group with a mean of 148.9 ±â€¯14.8 m s compared to mid septum (139.6 ±â€¯19.9 m s; p-value 0.003) and RVOT septum (139.6 ±â€¯14.8 m s; p-value 0.002) groups, respectively. There was no significant difference between mid-septal and RVOT septal pQRS duration. On multivariate analysis, female gender, baseline QRS duration and RVOT septal pacing were the only predictors for narrow pQRS duration (<150 msec). CONCLUSION: RV mid-septal and RVOT septal pacing were associated with significantly lower pQRS duration as compared with apical pacing. Based on multivariate analysis RVOT septal pacing appears to be preferred and more physiological pacing site.