Endocardial ablation of ventricular ectopic beats arising from the basal inferoseptal process of the left ventricle

Background Idiopathic ventricular ectopy (VE) shows predilection to sites within the left ventricular (LV) base such as the outflow tract/aortic sinuses, LV summit, and areas adjacent to the aortomitral continuity. We characterize VE arising from the inferior septum of the LV base that was successfully managed by LV endocardial ablation from the inferoseptal recess of the LV. Objective The purpose of this study was to determine the incidence, electrocardiographic (ECG) findings, electrophysiological findings, and anatomical features associated with VE arising from the basal inferoseptal process of the LV (ISP-LV) ablated using an LV endocardial approach via the inferoseptal recess of the LV. Methods A total of 425 consecutive patients undergoing VE ablation between January 1, 2012 and December 31, 2016 at 3 centers were evaluated. Demographic characteristics, ECG findings, and procedural data were analyzed for patients with ISP-LV VEs. Results Seven (1.5%) had a site of origin from the ISP-LV. Common ECG findings were a right bundle branch block concordant pattern or an atypical left bundle branch block early transition pattern, suggestive of a basal origin with a left superior axis, a biphasic QRS complex in lead aVR, and a small s wave in lead V6. Earliest activation was seen in an area below the outflow tract accessed from the inferoseptal recess inferior to the His bundle. In 3 cases, transient junctional rhythm was seen during ablation. All cases were ablated successfully with no complications. Conclusion VE arising from the ISP-LV represents a distinct subset of idiopathic arrhythmia and can be successfully treated by endocardial catheter ablation from the inferoseptal recess. They share common surface ECG and electrophysiological findings with special anatomical features that need recognition for successful catheter ablation

Remanufactured circular mapping catheters: safety, effectiveness and cost.

BACKGROUND: The use of remanufactured single-use devices (SUDs), including cardiac electrophysiology catheters, has become established in the USA and other health care systems but without much published scientific evaluation on the relative safety or efficacy of these devices. In the United Kingdom (UK), the use of remanufactured SUDs has not been routine. We performed a structured evaluation of the safety and efficacy of a remanufactured circular mapping catheter (Stryker® remanufactured Lasso NAV 2515) during its introduction in our centre. METHODS: We prospectively evaluated the performance of a remanufactured circular mapping catheter in 100 consecutive patients undergoing an AF ablation. Operator feedback was obtained, assessing the device appearance, ease of use and function. As an indirect measurement of efficacy, acute procedure metrics were compared to those in 100 propensity-matched cases performed by the same operators using a new device. Cost savings were calculated. RESULTS: No complication occurred in association with the remanufactured device. There was one reported failure of device malfunction-the flexion-extension mechanism of a remanufactured catheter and none in the matched-control group. There was satisfactory communication with the electro-anatomic mapping system. Ease of use of the remanufactured catheter was reported to be similar to a newly manufactured device. Procedural duration was similar with remanufactured devices and matched controls. With 100 cases using the remanufactured device, cost savings amounted to £30,444. CONCLUSIONS: The use of remanufactured circular mapping catheters is safe, efficient and reliable. Widespread use of remanufactured SUDs offers the possibility of significant economic benefit

Behind the counter: pharmacies and dispensing patterns of pharmacy attendants in Karachi.

BACKGROUND: There is little literature available on dispensing patterns and unsupervised sale of medicines from pharmacies in developing countries. OBJECTIVE: This study obtained background information on pharmacies assessed the level of training, knowledge and dispensing patterns of pharmacy attendants in Karachi. METHODOLOGY: This is a descriptive cross sectional study with convenient sampling. A structured questionnaire was used to interview pharmacy attendants. RESULTS: Of the 219 pharmacies surveyed, 62% reported more than 50 customers daily and 20% also sold items of general provision. Mean operating hours were 13. Only 24 (11%) had a visible license. On an average 3 attendants were employed per pharmacy. We interviewed one in each. Amongst the 219 interviewed, 77 (35%) were intermediate qualified and only 26 (12%) pharmacologically trained. Correct frequency of ORS administration was not known by 167 (76%) and 21% incorrectly suggested an anti-diarrhoeal preparation for viral diarrhoea in children. The knowledge of those with pharmacological training was significantly better. For respiratory tract infection in children approximately 60% did not know the correct dose of Paracetamol and Amoxicillin. Only 13 (6%) knew that Propanalol was contraindicated in hypertensive asthamatics. For Cotrimoxazole, metronidazole and lomotil only 40%, 21% and 15% respectively, were aware that these could not be dispensed without prescription. CONCLUSION: In the absence of trained pharmacists existing pharmacy attendants should be trained to improve drug-dispensing patterns

An integrated systems-level model of ochratoxin A toxicity in the zebrafish (Danio rerio) embryo based on NMR metabolic profiling

Ochratoxin A (OTA) is one of the most widespread mycotoxin contaminants of agricultural crops. Despite being associated with a range of adverse health effects, a comprehensive systems-level mechanistic understanding of the toxicity of OTA remains elusive. In the present study, metabolic profiling by high-resolution magic angle spinning (HRMAS) NMR, coupled to intact zebrafish embryos, was employed to identify metabolic pathways in relation to a systems-level model of OTA toxicity. Embryotoxicity was observed at sub-micromolar exposure concentrations of OTA. Localization of OTA, based on intrinsic fluorescence, as well as a co-localization of increased reactive oxygen species production, was observed in the liver kidney, brain and intestine of embryos. Moreover, HRMAS NMR showed significant alteration of metabolites related to targeting of the liver (i.e., hepatotoxicity), and pathways associated with detoxification and oxidative stress, and mitochondrial energy metabolism. Based on metabolic profiles, and complementary assays, an integrated model of OTA toxicity is, thus, proposed. Our model suggests that OTA hepatotoxicity compromises detoxification and antioxidant pathways, leading to mitochondrial membrane dysfunction manifested by crosstalk between pathways of energy metabolism. Interestingly, our data additionally aligns with a possible role of mitochondrial fusion as a "passive mechanism" to rescue mitochondrial integrity during OTA toxicity.Solid state NMR/Biophysical Organic Chemistr

Transvenous lead extraction: Experience of the Tandem approach.

BACKGROUND: Transvenous lead extraction (TLE) is important in the management of cardiac implantable electronic devices but carries risk. TLE is most commonly completed from the superior access, often with 'bail-out' support via the femoral approach. Superior and inferior access may be used in tandem, which has been proposed as an advance in safety and efficacy. AIM: To evaluate the safety and efficacy of the Tandem approach. METHOD: The 'Tandem' procedure entailed grasping of the targeted lead in the right atrium to provide countertraction as a rotational dissecting sheath was advanced over the lead from the subclavian access. Consecutive 'Tandem' procedures performed by a single operator between December 2020 - March 2023 in a single large-volume TLE centre were included and compared with the conventional superior approach (control) using 1:1 propensity score matching; patients were statistically matched for demographics. RESULTS: The Tandem in comparison to the conventional approach extracted leads of much greater dwell time (148.9±79 vs 108.6±77 months, p<0.01) in a shorter procedure duration (96±36 vs 127±67 minutes, p<0.01) but requiring more fluoroscopy (16.4±10.9 vs 10.8±14.9 minutes, p<0.01). The Tandem and control groups had similar clinical (100% vs 94.7%, p=0.07) and complete (94.8% vs 92.8%, p=0.42) success, with comparable minor (4% vs 6.7%, p=0.72) and major (0% vs 4%, p=0.25) complications; procedural (0% vs 1.3%, p=1) and 30-day (1.3% vs 4%, p=0.62) mortality were also similar. CONCLUSION: The Tandem procedure is as safe and effective as the conventional TLE. It can be applied to leads of a long dwell time with a potentially shorter procedure duration

Medium-Term Outcomes in COVID-19.

COVID-19 causes severe illness that results in morbidity and mortality. Electrocardiographic features, including QT prolongation, have been associated with poor acute outcomes; data on the medium-term outcomes remain scarce. This study evaluated the 1-year outcomes of patients who survived the acute COVID-19 infection. METHODS AND MATERIALS: Data of the 159 patients who survived the COVID-19 illness during the first wave (1 March 2020-18 May 2020) were collected. Patient demographics, laboratory findings and electrocardiography data were evaluated. Patients who subsequently died within 1-year of the index illness were compared to those who remained well. RESULTS: Of the 159 patients who had survived the index illness, 28 (17.6%) subsequently perished within 1-year. In comparison to the patients that were alive after 1-year, the deceased were older (68 vs. 83 years, p &lt; 0.01) and equally male (60.4% vs. 53.6%, p = 0.68), with a similar proportion of hypertension (59.5% vs. 57.1%, p = 0.68), diabetes (25.2% vs. 39.2%, p = 0.096) and ischaemic heart disease (11.5% vs. 7.1%, p = 0.54). The QTc interval for the alive and deceased patients shortened by a similar degree from the illness to post-COVID (-26 ± 33.5 vs. -20.6 ± 30.04 milliseconds, p = 0.5); the post-COVID R-R interval was longer in the alive patients compared to the deceased (818.9 ± 169.3 vs. 761.1 ± 61.2 ms, p = 0.02). A multivariate Cox regression analysis revealed that age (HR1.098 [1.045-1.153], p &lt; 0.01), diabetes (HR3.972 [1.47-10.8], p &lt; 0.01) and the post-COVID R-R interval (HR0.993 [0.989-0.996], p &lt; 0.01) were associated with 1-year mortality. CONCLUSIONS: The COVID-19-associated mortality risk extends to the post-COVID period. The QTc does recover following the acute illness and is not associated with outcomes; the R-R interval is a predictor of 1-year mortality

Comparative toxicometabolomics of perfluorooctanoic acid (PFOA) and next-generation perfluoroalkyl substances

) was significantly correlated with alkyl chain-length, and toxic concentrations were quantitatively similar to those reported previously for PFAS. Metabolic profiling of zebrafish embryos exposed to selected PFAS, specifically including PFOA and two representative PFECA (i.e., GenX and PFO3TDA), enabled elaboration of an integrated model of the metabolic pathways associated with toxicity of these representative PFAS. Alterations of metabolic profiles suggested targeting of hepatocytes (i.e., hepatotoxicity), as well as apparent modulation of neural metabolites, and moreover, were consistent with a previously proposed role of mitochondrial disruption and peroxisome proliferator-activated receptor (PPAR) activation as reflected by dysfunctions of carbohydrate, lipid and amino acid metabolism, and consistent with a previously proposed contribution of PFAS to metabolic syndrome. Taken together, it was generally concluded that toxicity of PFECA is quantitatively and qualitatively similar to PFOA, and these analogs, likewise, represent potential concerns as environmental toxicants.Solid state NMR/Biophysical Organic Chemistr

HL-1 cells express an inwardly rectifying K+ current activated via muscarinic receptors comparable to that in mouse atrial myocytes

An inwardly rectifying K^+ current is present in atrial cardiac myocytes that is activated by acetylcholine (I_{KACh}). Physiologically, activation of the current in the SA node is important in slowing the heart rate with increased parasympathetic tone. It is a paradigm for the direct regulation of signaling effectors by the Gβγ G-protein subunit. Many questions have been addressed in heterologous expression systems with less focus on the behaviour in native myocytes partly because of the technical difficulties in undertaking comparable studies in native cells. In this study, we characterise a potassium current in the atrial-derived cell line HL-1. Using an electrophysiological approach, we compare the characteristics of the potassium current with those in native atrial cells and in a HEK cell line expressing the cloned Kir3.1/3.4 channel. The potassium current recorded in HL-1 is inwardly rectifying and activated by the muscarinic agonist carbachol. Carbachol-activated currents were inhibited by pertussis toxin and tertiapin-Q. The basal current was time-dependently increased when GTP was substituted in the patch-clamp pipette by the non-hydrolysable analogue GTPγS. We compared the kinetics of current modulation in HL-1 with those of freshly isolated atrial mouse cardiomyocytes. The current activation and deactivation kinetics in HL-1 cells are comparable to those measured in atrial cardiomyocytes. Using immunofluorescence, we found GIRK4 at the membrane in HL-1 cells. Real-time RT-PCR confirms the presence of mRNA for the main G-protein subunits, as well as for M2 muscarinic and A1 adenosine receptors. The data suggest HL-1 cells are a good model to study IKAch