Outcomes with physiologic His bundle pacing in patients with narrow QRS complex.

BACKGROUND: In patients with narrow QRS complex, both ventricular and biventricular pacing is associated with increased cardiac morbidity and mortality. This risk is not decreased by ventricular pacing avoidance algorithms, which cause nonphysiologic atrioventricular (AV) delays. OBJECTIVE: This study aimed to report outcomes in patients with narrow QRS complex when the paced complex is in normal range and physiologic AV delays are programmed. METHODS: In 196 patients with QRS duration of 92 ± 10 ms, permanent pacing was done at the site of the His bundle electrogram. The pacemakers were then programmed to maintain physiologic AV delays and to increase heart rates in response to exercise. Patients received usual care and were observed for 3 years. RESULTS: The paced complex exhibited a delta wave, and the ventricular activation time, QRS axis, and lead I voltage remained in normal range. Physiologic programming resulted in His bundle pacing burden of 92%. In patients with decreased ejection fraction, there was significant improvement in left ventricular function, left ventricular dilation, and mitral regurgitation (P < .003). In patients with normal ejection fraction, left ventricular function remained normal without new valvular abnormalities. The 3-year all-cause mortality was 10%, and there was no increase in heart failure admissions. CONCLUSION: In patients with narrow QRS complex, when paced QRS morphology is maintained in normal range and AV dyssynchrony is avoided, His bundle pacing is associated with low all-cause mortality and improvement in abnormal echocardiographic parameters. The paced QRS morphology and physiologic AV delays may be important factors to evaluate in future trials of conduction system pacing.

Biosimilar Tenecteplase Versus Alteplase in Acute Ischemic Stroke: A Real World Study.

Background and Purpose: There is an unmet need for a more effective thrombolytic agent in acute ischemic stroke (AIS) management. Various studies and meta-analysis suggest tenecteplase (TNK) as non-inferior over alteplase (rTPA). The present single-center study compares biosimilar TNK and rTPA in a tertiary care setting. Methods: Data of patients who presented with AIS and underwent intravenous thrombolysis (IVT) were recruited retrospectively from January 2018 to July 2021. Primary efficacy outcome was a modified Rankin score (mRS) at 90 days dichotomized at < = 2. Qualitative and quantitative variables were assessed using Chi-square test and Student's t-test, respectively. Results: A total of 160 patients, 103 in the rTPA and 57 in TNK group, were analyzed. The baseline characteristics were well matched apart from hypertension. Large artery atherosclerosis was the most frequent subtype of stroke among the two groups. Good functional outcome was seen in 47.92% of patients TNK and 64.77% of patients in rTPA group (p = 0.069). No difference was seen in the rates of any ICH (p = 0.29) and mortality at 3 months (p = 0.32) among the two groups. Conclusion: This present study observed no difference in the efficacy and safety between biosimilar TNK and rTPA. Our findings are in concordance with published trials showing equivalence between the two molecules.

Evidence for concealed fasciculo-ventricular connections as revealed by His bundle pacing.

BACKGROUND: It is almost 100 years ago since Mahaim described the so-called paraspecific connections between the ventricular conduction axis and the crest of the muscular ventricular septum, believing such pathways to be ubiquitous. These pathways, however, have yet to be considered as potential pathways for septal activation during His bundle pacing. MATERIALS: So as to explore the hypothesis that specialised septal pathways might provide the substrate for septal activation during His bundle pacing, we compared the findings from 22 serially sectioned histological datasets and 34 different individuals undergoing His bundle pacing. RESULTS: We found histologically specialised pathways connecting the branching component of the atrioventricular conduction axis with the crest of the muscular ventricular septum in almost four-fifths of the histological datasets. In 32 of 34 patients undergoing His bundle pacing, the QRS complex closely resembled published images of known conduction through fasciculo-ventricular pathways. In only two patients was a delta wave not seen at any pacing voltages. Capture of these connections varied according to pacing voltage, a finding which correlated with the distance of the pathways from the site of penetration of the ventricular conduction axis. Ventricular activation times remained normal in the presence of the delta wave at higher pacing voltage but were prolonged at lower voltages. CONCLUSIONS: Our histologic findings confirm fasciculo-ventricular connections, initially described by Mahaim as being paraspecific, are likely ubiquitous. Analysis of 12-lead electrocardiograms leads us to conclude that fasciculo-ventricular pathways, concealed during sinus rhythm, become manifest with His bundle pacing.

Comparison of Disease Profiles and Three-Month Outcomes of Patients with Neurological Disorders with and without COVID-19: An Ambispective Cohort Study.

Objective: Neurological emergencies saw a paradigm shift in approach during the coronavirus disease-2019 (COVID-19) pandemic with the challenge to manage patients with and without COVID-19. We aimed to compare the various neurological disorders and 3 months outcome in patients with and without SARS-CoV-2 infection. Methods: In an ambispective cohort study design, we enrolled patients with and without SARS CoV-2 infection coming to a medical emergency with neurological disorders between April 2020 and September 2020. Demographic, clinical, biochemical, and treatment details of these patients were collected and compared. Their outcomes, both in-hospital and at 3 months were assessed by the modified Rankin Scale (mRS). Results: Two thirty-five patients (235) were enrolled from emergency services with neurological disorders. Of them, 81 (34.5%) were COVID-19 positive. The mean (SD) age was 49.5 (17.3) years, and the majority of the patients were male (63.0%). The commonest neurological diagnosis was acute ischemic stroke (AIS) (43.0%). The in-hospital mortality was higher in the patients who were COVID-19 positive (COVID-19 positive: 29 (35.8%) versus COVID-19 negative: 12 (7.8%), P value: <0.001). The 3 months telephonic follow-up could be completed in 73.2% of the patients (142/194). Four (12.1%) deaths occurred on follow-up in the COVID-19 positive versus fifteen (13.8%) in the COVID-19 negative patients (P value: 1.00). The 3-month mRS was worse in the COVID-19 positive group (P value <0.001). However, this was driven by higher in-hospital morbidity and mortality in COVID-19 positive patients. Conclusion: Patients with neurological disorders presenting with COVID-19 infection had worse outcomes, including in-hospital and 3 months disability.

Rivaroxaban as Therapy for Saphenous Venous Graft Failure due to Venous Outflow Mismatch.

Background: Recurrent angina and long-term occlusion following coronary artery bypass graft surgery is often treated with percutaneous coronary intervention, a high-risk intervention for distal embolization. Here, we present the utilization of the novel oral anticoagulant, rivaroxaban, in the treatment of saphenous vein graft thrombosis with complete resolution of the thrombus secondary to graft outflow mismatch. Case Presentation. A 69-year-old man with triple coronary artery bypass grafting using a saphenous vein and left internal mammary artery, performed in 2017, presented at our hospital for recurrent angina. Coronary angiography revealed a patent LIMA to LAD and a large clot burden in the venous conduit to the first OM/terminal circumflex-theorized to be due to an outflow mismatch of the large saphenous vein to the native artery resulting in stasis. Instead of percutaneous coronary intervention, he was treated with rivaroxaban 20 mg once a day. The angiography 4 weeks after starting rivaroxaban showed complete resolution of the thrombus. Conclusion: Rivaroxaban could become a potential treatment option in thrombus reversal due to static venous flow with subsequent long-term patency of the graft. Additionally, its use may be indicated in the generalized prevention of VGF.

Third Line Antiretroviral Treatment in India: Cohort Analysis and Treatment Outcomes from a Public Health Facility.

The National Programme in India provides free third-line antiretroviral treatment (ART) for all people living with HIV (PLHIV). Data of 232 PLHIV initiated on third-line ART from a single center in New Delhi were retrospectively analyzed for virological suppression at 6 and 12 months, factors predicting nonresponse, retention in care, and mortality from June 2016 till December 2019. The mean age at third-line ART initiation was 39.54 ± 11.08 years, 71.5% were males, and 55.02% had HIV duration of >10 years. The mean CD4 count at third-line ART initiation was 260.04 ± 200.4/mm3, and the median viral load (VL) at second-line failure was 61,253 copies/mL (interquartile range, 12,599-315,497 copies/mL). Of the patients, 71.52% achieved virological suppression at 6 months (n = 151), and this was maintained at 12 months-72% (n = 50). The mortality rate among those still in active care was 8.69% (18/207). PLHIV who did not attain virological suppression at 6 months had significantly shorter duration on second-line ART (p = 0.0002), lower peak CD4 achieved on second-line ART (p = 0.039), higher VL at second-line failure (p = 0.012), and lower body weight (p < 0.0001). On univariate analysis, lower CD4 peak on second-line ART (p = 0.019), lower CD4 count at third-line ART initiation (p = 0.004), and lower body weight (p = 0.0002) were significantly predictive of virological nonsuppression at 6 months. Successful implementation of a third-line ART program can indeed be done through a public health approach. Intensive adherence support, nutritional rehabilitation, and regular viral load monitoring are crucial for improved clinical and virological outcomes.

Perceived social support, depression and their impact on quality of life of people living with HIV in India.

Universal access to Antiretroviral Treatment (ART) has transformed HIV/AIDS into a chronic disease and issues like social support and Quality of life (QOL) have emerged as important components of care. Perceived social support influences QOL in People Living with HIV (PLHIV), though this has not been studied well in India. PLHIV were assessed for Social Support using the Multidimensional Scale of Perceived Social Support (MSPSS) and QOL was assessed with the Medical Outcomes Study HIV Health Survey (MOS-HIV) questionnaire. The factors impacting social support and its effect of on QOL were analysed. Amongst the 109 study subjects, 62 (56.9%) were men, 47 (43.1%) were women, mean age was 35 ± 7.5 years, 85.3% had WHO stage 1 disease and 80 (73.4%) were receiving ART. Only 43.1% subjects perceived high overall social support. Social support (from family/friends/others) was associated positively with physical functioning (p = 0.001), social and cognitive functioning (p = 0.000) and significantly inversely associated with depression (p = 0.002). Higher perceived social support was seen to correlate with higher CD4 count (Peak, Nadir and Current; p < 0.05) and better adherence (p = 0.003). It is concluded that social support, including support from beyond family, have a significant impact on clinical endpoints and QOL in PLHIV.

Discovery of Dihydropyrrolo[1,2-a]pyrazin-3(4H)-one-Based Second-Generation GluN2C- and GluN2D-Selective Positive Allosteric Modulators (PAMs) of the N-Methyl-d-Aspartate (NMDA) Receptor.

The N-methyl-d-aspartate receptor (NMDAR) is an ion channel that mediates the slow, Ca2+-permeable component of glutamatergic synaptic transmission in the central nervous system (CNS). NMDARs are known to play a significant role in basic neurological functions, and their dysfunction has been implicated in several CNS disorders. Herein, we report the discovery of second-generation GluN2C/D-selective NMDAR-positive allosteric modulators (PAMs) with a dihydropyrrolo[1,2-a]pyrazin-3(4H)-one core. The prototype, R-(+)-EU-1180-453, exhibits log unit improvements in the concentration needed to double receptor response, lipophilic efficiency, and aqueous solubility, and lowers cLogP by one log unit compared to the first-generation prototype CIQ. Additionally, R-(+)-EU-1180-453 was found to increase glutamate potency 2-fold, increase the response to maximally effective concentration of agonist 4-fold, and the racemate is brain-penetrant. These compounds are useful second-generation in vitro tools and a promising step toward in vivo tools for the study of positive modulation of GluN2C- and GluN2D-containing NMDA receptors.