Electrocardiographic predictors of clinical outcomes in nonischemic cardiomyopathy patients with left bundle branch area pacing cardiac resynchronization therapy.

BACKGROUND: Paced QRS morphology may vary during left bundle branch area pacing (LBBAP) per the pacing location. It remains unclear whether electrocardiographic changes observed during LBBAP can predict clinical outcomes. OBJECTIVE: We aimed to assess correlation between characteristics of paced QRS on the electrocardiogram and clinical outcomes in heart failure patients with nonischemic cardiomyopathy. METHODS: Of 79 consecutive heart failure patients receiving LBBAP, 59 patients were included in this prospective study after exclusions. LBBAP was performed using Medtronic 3830 lead. Patients were assigned to various groups on the basis of paced QRS morphology in lead V1 (qR and Qr), QRS axis (normal, left, or right), and V6 R-wave peak time (RWPT, ≤80 ms or >80 ms) to compare echocardiographic outcomes. RESULTS: RWPT was significantly shorter (75.7 ± 17.5 ms vs 85.3 ± 11.3 ms; P = .014), transition during threshold testing was more commonly observed (81.5% vs 53%; P = .02), and improvement in left ventricular ejection fraction (LVEF) was significantly greater in the qR group (21.4% ± 6.4% vs 16.4% ± 8.3%; P = .013) compared with the Qr group. RWPT or LVEF did not differ in patients with different paced QRS axis (P > .05). Whereas qR morphology and presence of transition during threshold testing independently predicted LVEF improvement, RWPT lacked predictive value. Nonresponders had greater incidence of loss of R' (P = .009) and prolonged RWPT (P = .003) on follow-up compared with average responders and superresponders. CONCLUSION: Paced qR morphology and transition during threshold testing predicted greater improvement in LVEF, whereas RWPT lacked predictive value. Loss of terminal R in lead V1 and prolongation of RWPT on follow-up prognosticated nonresponse to LBBAP.

Correlation of extent of left ventricular endocardial unipolar low-voltage zones with ventricular tachycardia in nonischemic cardiomyopathy.

BACKGROUND: Endocardial electrogram (EGM) characteristics in nonischemic cardiomyopathy (NICM) have not been explored adequately for prognostication. OBJECTIVE: We aimed to study correlation of bipolar and unipolar EGM characteristics with left ventricular ejection fraction (LVEF) and ventricular tachycardia (VT) in NICM. METHODS: Electroanatomic mapping of the left ventricle was performed. EGM characteristics were correlated with LVEF. Differences between groups with and without VT and predictors of VT were studied. RESULTS: In 43 patients, unipolar EGM variables had better correlation with baseline LVEF than bipolar EGM variables: unipolar voltage (r = +0.36), peak negative unipolar voltage (r = -0.42), peak positive unipolar voltage (r = +0.38), and percentage area of unipolar low-voltage zone (LVZ; r = -0.41). Global mean unipolar voltage (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.2-0.8), extent of unipolar LVZ (HR, 1.6; 95% CI, 1.1-2.3), and percentage area of unipolar LVZ (HR, 1.6; 95% CI, 1.1-2.3) were significant predictors of VT. For classification of patients with VT, extent of unipolar LVZ had an area under the curve of 0.82 (95% CI, 0.69-0.95; P < .001), and percentage area of unipolar LVZ had an area under the curve of 0.83 (95% CI, 0.71-0.96; P = .01). Cutoff of >3 segments for extent of unipolar LVZ had the best diagnostic accuracy (sensitivity, 90%; specificity, 67%) and cutoff of 33% for percentage area of unipolar LVZ had the best diagnostic accuracy (sensitivity, 95%; specificity, 60%) for VT. CONCLUSION: In NICM, extent and percentage area of unipolar LVZs are significant predictors of VT. Cutoffs of >3 segments of unipolar LVZ and >33% area of unipolar LVZ have good diagnostic accuracies for association with VT.

Efficacy of left bundle branch area pacing versus biventricular pacing in patients treated with cardiac resynchronization therapy: Select site - cohort study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is typically attempted with biventricular (BiV) pacing. One-third of patients are nonresponders. Left bundle branch area pacing (LBBAP) has been evaluated as an alternative means. OBJECTIVE: The purpose of this study was to assess the feasibility and clinical response of permanent LBBAP as an alternative to BiV pacing. METHODS: Of 479 consecutive patients referred with heart failure, 50 with BiV-CRT and 51 with LBBAP-CRT were included in this analysis after study exclusions. Quality-of-Life (QoL) assessments, echocardiographic measurements, and New York Heart Association (NYHA) class were obtained at baseline and at 6-monthly intervals. RESULTS: There were no differences in baseline characteristics between groups (all P > .05). Clinical outcomes such as left ventricular ejection fraction, left ventricular end-systolic volume, QoL, and NYHA class were significantly improved for both pacing groups compared to baseline. The LBBAP-CRT group showed greater improvement in left ventricular ejection fraction at 6 months (P = .001) and 12 months (P = .021), accompanied by greater reduction in left ventricular end-systolic volume (P = .007). QRS duration < 120 ms (baseline 160.82 ± 21.35 ms vs 161.08 ± 24.48 ms) was achieved in 30% in the BiV-CRT group vs 71% in the LBBAP-CRT group (P ≤ .001). Improvement in NYHA class (P = .031) and QoL index was greater (P = .014). Reduced heart failure admissions (P = .003) and health care utilization (P < .05) and improved lead performance (P < .001) were observed in the LBBAP-CRT group. CONCLUSION: LBBAP-CRT is feasible and effective CRT. It results into a meaningful improvement in QoL and reduction in health care utilization. This can be offered as an alternative to BiV-CRT or potentially as first-line therapy.

Characteristics of the phenotype of mixed cardiomyopathy in patients with implantable cardioverter-defibrillators.

BACKGROUND OR PURPOSE: The prognosis of m ixed cardiomyopathy (CMP) in patients with implanted cardioverter-defibrillators (ICDs) has not been investigated. We aim to study the demographic, clinical, device therapies and survival characteristics of mixed CMP in a cohort of patients implanted with a defibrillator. METHODS: The term mixed CMP was used to categorise patients with impaired left ventricular ejection fraction attributed to documented non-ischemic triggers with concomitant moderate coronary artery disease. This is a single center observational cohort of 526 patients with a mean follow-up of 8.7 ± 3.5 years. RESULTS: There were 42.5% patients with ischemic cardiomyopathy (ICM), 26.9% with non-ischemic cardiomyopathy (NICM) and 30.6% with mixed CMP. Mixed CMP, compared to NICM, was associated with higher mean age (69.1 ± 9.6 years), atrial fibrillation (55.3%) and greater incidence of comorbidities. The proportion of patients with mixed CMP receiving device shocks was 23.6%, compared to 18.4% in NICM and 27% in ICM. The VT cycle length recorded in mixed CMP (281.6 ± 43.1 ms) was comparable with ICM (282.5 ± 44 ms; p = 0.9) and lesser than NICM (297.7 ± 48.7 ms; p = 0.1). All-cause mortality in mixed CMP (21.1%) was similar to ICM (20.1%; p = 0.8) and higher than NICM (15.6%; p = 0.2). The Kaplan-Meier curves revealed hazards of 1.57 (95% CI: 0.91, 2.68) for mixed CMP compared to NICM. CONCLUSION: In a cohort of patients with ICD, the group with mixed CMP represents a phenotype predominantly comprised of the elderly with a higher incidence of comorbidities. Mixed CMP resembles ICM in terms of number of device shocks and VT cycle length. Trends of long-term prognosis of patients with mixed CMP are worse than NICM and similar to ICM.

Long-term mortality in heart failure with mid-range ejection fraction: systematic review and meta-analysis.

AIMS: Heart failure patients with mid-range ejection fraction (HFmrEF) have overlapping clinical features, compared with patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). We aim to perform a meta-analysis of studies reporting long-term outcomes in HFmrEF compared with HFrEF and HFpEF. METHODS AND RESULTS: Data from 18 eligible large-scale studies including 126 239 patients were pooled. Patients with HFmrEF had a lower risk of all-cause death than those with HFrEF [risk ratio (RR) = 0.92; 95% CI = 0.85-0.98; P < 0.001]. This significant difference was seen in the follow-up at 1, 2, and 3 years. Patients with HFmrEF had significantly lower risk of cardiovascular (CV) deaths than HFrEF (RR = 0.77; 95% CI = 0.65-0.92; P < 0.001). Subgroup analysis showed that studies recruiting >50% of males had higher risk of deaths with HFrEF (RR = 1.15; 95% CI = 1.04-1.26; P = 0.006). When compared with HFpEF, patients with HFmrEF had comparable risk of all-cause death (RR = 1.02; 95% CI = 0.96-1.09; P = 0.53). Similarly, there were no differences in the 1, 2, and 3 year deaths; CV and non-CV deaths were insignificant between HFmrEF and HFpEF. CONCLUSIONS: The results of the study support that HFmrEF has better prognosis than HFrEF but similar prognosis when compared with HFpEF. Gender disparity between studies seems to influence the results between HFmrEF and HFrEF. Transition in left ventricular ejection fraction (LVEF), which could not be addressed in the study, may play a decisive role in determining outcomes. PROSPERO review registration number CRD42021277107.

Prolonged endoscopic retrograde cholangiopancreatography results in higher rates of pancreatitis and unplanned hospitalisation.

BACKGROUND AND AIM: Although complications from endoscopic retrograde cholangiopancreatography (ERCP) are well described, procedure duration has received scant attention. The relationship between ERCP duration and patient demographics, indications, results and complications were examined. METHODS: A contemporaneously recorded database of 2572 consecutive ERCPs performed between 2008 and 2018 by a single endoscopist was analysed. Those taking under 40 min were compared with those taking over 40 min. RESULTS: Of 2572 cases, 2213 took under 40 min and 359 took over 40 min. Emergency cases (relative risk 2.10), older age (66.6 vs 61.6 years p value < 0.01) and no previous sphincterotomy (relative risk 1.94) were factors which resulted in prolonged procedures. The indication of change or removal of stent for benign conditions resulted in fewer prolonged procedures (relative risk 0.37). Indications of pancreatitis, cholangitis and positive intraoperative cholangiogram were not associated with procedure length. Findings of biliary stricture(s) (relative risk 2.02) and failure to cannulate desired duct (relative risk 3.69) were associated with prolonged procedures. Choledocholithiasis (relative risk 0.62), dilated bile duct without stricture/stone (relative risk 0.46) and normal ductal anatomy (relative risk 0.50) resulted in fewer prolonged procedures. Procedures taking over 40 min had increased risks of complications resulting in unplanned or prolongation of hospitalisation (relative risk 1.41) and pancreatitis (relative risk 1.74). CONCLUSIONS: Prolonged procedures had increased rates of pancreatitis and unplanned/prolonged hospitalisation. Failed access to desired duct, advanced age, biliary strictures, no previous sphincterotomy and unplanned emergency cases were associated with prolonged procedures.

A Camera-Trap Home-Range Analysis of the Indian Leopard (Panthera pardus fusca) in Jaipur, India.

The suitability of the camera trap-retrap method was explored for identifying territories and studying the spatial distribution of leopards (Panthera pardus fusca) in the Jhalana Reserve Forest, Jaipur, India. Data from two years (November 2017 to November 2019, N = 23,208 trap-hours) were used to provide estimates of minimum home-range size and overlap. We conducted home-range analysis and estimation, using the minimum convex polygon (MCP) method with geographic information system (GIS) tools. We are aware of the limitations and advantages of camera trapping for long-term monitoring. However, the limitations of the research permit allowed only the use of camera traps to estimate the home ranges. A total of 25 leopards were identified (male = 8, female = 17). No territorial exclusivity was observed in either of the sexes. However, for seven females, we observed familial home-range overlaps wherein daughters established home ranges adjacent to or overlapping their natal areas. The median home range, as calculated from the MCP, was 305.9 ha for males and 170.3 ha for females. The median percentage overlap between males was 10.33%, while that between females was 3.97%. We concluded that camera trapping is an effective technique to map the territories of leopards, to document inter- and intraspecific behaviors, and to elucidate how familial relationships affect dispersal.

PREVEntion and regReSsive Effect of weight-loss and risk factor modification on Atrial Fibrillation: the REVERSE-AF study.

Aims: Atrial fibrillation (AF) is a progressive disease. Obesity is associated with progression of AF. This study evaluates the impact of weight and risk factor management (RFM) on progression of the AF. Methods and results: As described in the Long-Term Effect of Goal-Directed Weight Management in an Atrial Fibrillation Cohort: A Long-Term Follow-Up (LEGACY) Study, of 1415 consecutive AF patients, 825 had body mass index ≥ 27 kg/m2 and were offered weight and RFM. After exclusion, 355 were included for analysis. Weight loss was categorized as: Group 1 (<3%), Group 2 (3-9%), and Group 3 (≥10%). Change in AF type was determined by clinical review and 7-day Holter yearly. Atrial fibrillation type was categorized as per the Heart Rhythm Society consensus. There were no differences in baseline characteristic or follow-up duration between groups (P = NS). In Group 1, 41% progressed from paroxysmal to persistent and 26% from persistent to paroxysmal or no AF. In Group 2, 32% progressed from paroxysmal to persistent and 49% reversed from persistent to paroxysmal or no AF. In Group 3, 3% progressed to persistent and 88% reversed from persistent to paroxysmal or no AF (P < 0.001). Increased weight loss was significantly associated with greater AF freedom: 45 (39%) in Group 1, 69 (67%) in Group 2, and 116 (86%) in Group 3 (P ≤ 0.001). Conclusion: Obesity is associated with progression of the AF disease. This study demonstrates the dynamic relationship between weight/risk factors and AF. Weight-loss management and RFM reverses the type and natural progression of AF.

Cost-Effectiveness and Clinical Effectiveness of the Risk Factor Management Clinic in Atrial Fibrillation: The CENT Study.

BACKGROUND: Atrial fibrillation (AF) imposes a substantial cost burden on the healthcare system. Weight and risk factor management (RFM) reduces AF burden and improves the outcomes of AF ablation. OBJECTIVES: This study sought to evaluate the cost and clinical effectiveness of integrating RFM into the overall management of AF. METHODS: Of 1,415 consecutive patients with symptomatic AF, 825 patients had body mass index ≥27 kg/m2. After screening for exclusion criteria, the final cohort comprised 355 patients: 208 patients who opted for RFM and 147 control subjects and were followed by 3 to 6 monthly clinic review, 7-day Holter monitoring, and AF Symptom Score. A decision analytical model calculated the incremental cost-effectiveness ratios of cost per unit of global well-being gained and unit of AF burden reduced. RESULTS: There were no differences in baseline characteristics or follow-up duration (p = NS). Arrhythmia-free survival was better in the RFM compared with control subjects (Kaplan-Meier: 79% vs. 44%; p < 0.001). At follow-up, RFM group had less unplanned specialist visits (0.19 ± 0.40 vs. 1.94 ± 2.00; p < 0.001), hospitalizations (0.74 ± 1.3 vs. 1.05 ± 1.60; p = 0.03), cardioversions (0.89 ± 1.50 vs. 1.51 ± 2.30; p = 0.002), emergency presentations (0.18 ± 0.50 vs. 0.76 ± 1.20; p < 0.001), and ablation procedures (0.60 ± 0.69 vs. 0.72 ± 0.86; p = 0.03). Antihypertensive (0.53 ± 0.70 vs. 0.78 ± 0.60; p = 0.04) and antiarrhythmic (0.26 ± 0.50 vs. 0.91 ± 0.60; p = 0.003) use declined in RFM. The RFM group had an increase of 0.1930 quality-adjusted life years and a cost saving of $12,094 (incremental cost-effectiveness ratios of $62,653 saved per quality-adjusted life years gained). CONCLUSIONS: A structured physician-directed RFM program is clinically effective and cost saving.

Pulmonary Delivery of Anti-Tubercular Drugs Using Ligand Anchored pH Sensitive Liposomes for the Treatment of Pulmonary Tuberculosis.

BACKGROUND: Mycobacterium tuberculosis (M. TB) remains the prime cause of bacterial mortality and morbidity world-wide. Therefore, effective delivery and targeting of drug to the cellular tropics is essentially required to generate significant results for tuberculosis treatment. The aim of the present study was to develop and characterize ligand anchored pH sensitive liposomes (TPSL) as dry powder inhaler for the targeted delivery of drugs in the target site i.e. lungs. METHOD: Ligand anchored PSL (TPSL) was prepared by thin film hydration for the combined delivery of Isoniazid (INH) and Ciprofloxacin HCl (CIP HCl) using 4-aminophenyl-α-D mannopyranoside (Man) as surface functionalized ligand and characterized using different parameters. RESULTS: It was observed that size of the ligand anchored liposomes (TPSL) was slightly more than the non-ligand anchored liposomes (PSL). Drug release was studied at different pH for 24 hrs and it was observed that liposomes exhibited slow release at alkaline pH (58-64%) as compared to macrophage pH (81-87%) where it increased dramatically due to the destabilization of pH sensitive liposome (PSL). In vitro cellular uptake study showed that much higher concentration was achieved in the alveolar macrophage using ligand anchored liposomes as compared to its counterpart. In vivo study showed that maximum drug accumulation was achieved in the lung by delivering drug using ligand anchored PSL as compared to conventional PSL. CONCLUSION: It was concluded that ligand anchored pH sensitive liposome is one of the promising systems for the targeted drug therapy in pulmonary tuberculosis.

Stimuli-responsive hydrogels in drug delivery and tissue engineering.

Hydrogels are the three-dimensional network structures obtained from a class of synthetic or natural polymers which can absorb and retain a significant amount of water. Hydrogels are one of the most studied classes of polymer-based controlled drug release. These have attracted considerable attention in biochemical and biomedical fields because of their characteristics, such as swelling in aqueous medium, biocompatibility, pH and temperature sensitivity or sensitivity towards other stimuli, which can be utilized for their controlled zero-order release. The hydrogels are expected to explore new generation of self-regulated delivery system having a wide array of desirable properties. This review highlights the exciting opportunities and challenges in the area of hydrogels. Here, we review different literatures on stimuli-sensitive hydrogels, such as role of temperature, electric potential, pH and ionic strength to control the release of drug from hydrogels.

Pulmonary delivery of antitubercular drugs using spray-dried lipid-polymer hybrid nanoparticles.

The present study aimed to develop lipid-polymer hybrid nanoparticles (LPNs) for the combined pulmonary delivery of isoniazid (INH) and ciprofloxacin hydrochloride (CIP HCl). Drug-loaded LPNs were prepared by the double-emulsification solvent evaporation method using the three-factor three-level Box-Behnken design. The optimized formulation had a size of 111.81 ± 1.2 nm, PDI of 0.189 ± 1.4, and PDE of 63.64 ± 2.12% for INH-loaded LPN, and a size of 172.23 ± 2.31 nm, PDI of 0.169 ± 1.23, and PDE of 68.49 ± 2.54% for CIP HCl-loaded LPN. Drug release was found to be sustained and controlled at lower pH and followed the Peppas model. The in vitro uptake study in alveolar macrophage (AM) showed that uptake of the drugs was increased significantly if administered in the form of LPN. The stability study proved the applications of adding PLGA in LPN as the polymeric core, which leads to a much more stable product as compared to other novel drug delivery systems. Spray drying was done to produce an inhalable, dry, powdered form of drug-loaded LPN. The spray-dried (SD) powder was equally capable of producing nano-aggregates having morphology, density, flowability and reconstitutibility in the range ideal for inhaled drug delivery. The nano aggregates produced by spray drying manifested their aerosolization efficiency in terms of the higher emitted dose and fine particle fraction with lower mass median aerodynamic diameter. The in vivo study using pharmacokinetic and pharmacodynamic approaches revealed that maximum internalization efficiency was achieved by delivering LPN in SD powdered forms by pulmonary route.

Stimuli-sensitive systems--an emerging delivery system for drugs.

OBJECTIVES: Development of controlled and sustained drug delivery system (DDS) remains a great thrust of human beings for the successful delivery of drugs due to various drawbacks of existing systems. In order to overcome these drawbacks, various stimuli-sensitive DDSs were developed in the recent years. KEY FINDINGS: Stimuli are a state of responsiveness to sensory stimulation or excitability. Stimuli sensitive systems are those systems which deal with the changes in the physiology of body with respective to the environment changes. These systems may be very beneficial for the controlled and sustained delivery of drug in the body if proper work would be carried out on these types of systems. Controlled drug delivery became the standard criteria in modern pharmaceutical product design and an intensive research is still going on in achieving much better drug product with features like effectiveness, reliability, and safety. Many changes like photo and light, temperature, pH, ion, glucose, and redox affect the release of drug from the delivery system. These stimuli-sensitive systems are used for various purposes in various forms like in parenteral, ocular, peroral, rectal, vaginal, nasal, dermal and transdermal drug delivery. SUMMARY: Various literature surveys revealed that stimuli-sensitive DDSs can be explored as a potential tool for the delivery of a variety of macromolecules that are not effectively delivered by conventional techniques.

DEVELOPMENT AND CHARACTERIZATION OF GLUCOSE SENSITIVE HYDROGELS FOR THE TREATMENT OF DIABETES MELLIT.

Development of stimuli-sensitive hydrogels for the delivery of drug involves the development of matrices that are glucose-sensitive and have strong sensing properties so that the developed system can sense the level of glucose and release the medicament in response to blood glucose level. In the present study an attempt has been made to develop a glucose sensitive hydrogel system which modulates the release of an anti-diabetic drug in response to the blood glucose level in the body. The hydrogel system was prepared by gas foaming technique using chitosan and polyvinyl alcohol (PVA) as polymer and glutaraldehyde as cross-linking agent. Metformin was used as a drug candidate because of its short biological half life (6.25±0.5 hrs). The prepared glucose sensitive hydrogel system has characterized using different parameters. It was observed that hydrogel swelled and deswelled reversibly depending on the pH and glucose sensitivity of the medium and has suitable mechanical properties. In-vitro results showed that the enzymatically immobilized hydrogel was sensitive to both pH and glucose for effective release of drug. It was found that higher the concentration of glucose in the medium, higher the amount of drug released from the hydrogel. In vivo results showed that glucose oxidase leads to reduction in blood glucose level in response to variable glucose concentration in the body thus achieving the desired therapeutic levels in the body . The present study showed that glucose sensitive hydrogels not only are efficient in controlling the physiological blood glucose level but also provide for a sustained and controlled release of drugs having short biological half life.

Impact of CARDIOrespiratory FITness on Arrhythmia Recurrence in Obese Individuals With Atrial Fibrillation: The CARDIO-FIT Study.

BACKGROUND: Obesity begets atrial fibrillation (AF). Although cardiorespiratory fitness is protective against incident AF in obese individuals, its effect on AF recurrence or the benefit of cardiorespiratory fitness gain is unknown. OBJECTIVES: This study sought to evaluate the role of cardiorespiratory fitness and the incremental benefit of cardiorespiratory fitness improvement on rhythm control in obese individuals with AF. METHODS: Of 1,415 consecutive patients with AF, 825 had a body mass index ≥27 kg/m(2) and were offered risk factor management and participation in a tailored exercise program. After exclusions, 308 patients were included in the analysis. Patients underwent exercise stress testing to determine peak metabolic equivalents (METs). To determine a dose response, cardiorespiratory fitness was categorized as: low (<85%), adequate (86% to 100%), and high (>100%). Impact of cardiorespiratory fitness gain was ascertained by the objective gain in fitness at final follow-up (≥2 METs vs. <2 METs). AF rhythm control was determined using 7-day Holter monitoring and AF severity scale questionnaire. RESULTS: There were no differences in baseline characteristics or follow-up duration between the groups defined by cardiorespiratory fitness. Arrhythmia-free survival with and without rhythm control strategies was greatest in patients with high cardiorespiratory fitness compared to adequate or low cardiorespiratory fitness (p < 0.001 for both). AF burden and symptom severity decreased significantly in the group with cardiorespiratory fitness gain ≥2 METs as compared to <2 METs group (p < 0.001 for all). Arrhythmia-free survival with and without rhythm control strategies was greatest in those with METs gain ≥2 compared to those with METs gain <2 in cardiorespiratory fitness (p < 0.001 for both). CONCLUSIONS: Cardiorespiratory fitness predicts arrhythmia recurrence in obese individuals with symptomatic AF. Improvement in cardiorespiratory fitness augments the beneficial effects of weight loss. (Evaluating the Impact of a Weight Loss on the Burden of Atrial Fibrillation [AF] in Obese Patients; ACTRN12614001123639).

Long-Term Effect of Goal-Directed Weight Management in an Atrial Fibrillation Cohort: A Long-Term Follow-Up Study (LEGACY).

BACKGROUND: Obesity and atrial fibrillation (AF) frequently coexist. Weight loss reduces the burden of AF, but whether this is sustained, has a dose effect, or is influenced by weight fluctuation is unknown. OBJECTIVES: This study sought to evaluate the long-term impact of weight loss and weight fluctuation on rhythm control in obese individuals with AF. METHODS: Of 1,415 consecutive patients with AF, 825 had a body mass index ≥ 27 kg/m(2) and were offered weight management. After screening for exclusion criteria, 355 were included in this analysis. Weight loss was categorized as group 1 (≥ 10%), group 2 (3% to 9%), and group 3 (<3%). Weight trend and/or fluctuation was determined by yearly follow-up. We determined the impact on the AF severity scale and 7-day ambulatory monitoring. RESULTS: There were no differences in baseline characteristics or follow-up among the groups. AF burden and symptom severity decreased more in group 1 compared with groups 2 and 3 (p < 0.001 for all). Arrhythmia-free survival with and without rhythm control strategies was greatest in group 1 compared with groups 2 and 3 (p < 0.001 for both). In multivariate analyses, weight loss and weight fluctuation were independent predictors of outcomes (p < 0.001 for both). Weight loss ≥ 10% resulted in a 6-fold (95% confidence interval: 3.4 to 10.3; p < 0.001) greater probability of arrhythmia-free survival compared with the other 2 groups. Weight fluctuation >5% partially offset this benefit, with a 2-fold (95% confidence interval: 1.0 to 4.3; p = 0.02) increased risk of arrhythmia recurrence. CONCLUSIONS: Long-term sustained weight loss is associated with significant reduction of AF burden and maintenance of sinus rhythm. (Long-Term Effect of Goal directed weight management on Atrial Fibrillation Cohort: A 5 Year follow-up study [LEGACY Study]; ACTRN12614001123639).

Development and characterization of nanoemulsion as carrier for the enhancement of bioavailability of artemether.

The present study aimed to develop a kinetically stable nanoemulsion of artemether with improved solubility, stability and oral bioavailability. Nanoemulsion was prepared by ultrasonication technique using internal oil phase (consisted of the drug dissolved in coconut oil and span 80) and external phase (comprising tween 80 and ethanol dissolved in water). The formulations were optimized using various parameters like percentage transmittance, refractive index, drug content, viscosity, zeta potential and release rate. Stability studies were conducted for a period of 90 days using stability chambers. In vivo studies of the developed formulations were conducted on Wistar rats and data were analyzed statistically. The nanoemulsion as observed under transmission electron microscope were found to be spherical in shape with an average size of 79.0 nm and a zeta potential of -15 mV which indicated of good electrokinetic stability of nanoemulsion . Nanoemulsion was found to be clear and transparent in appearance with a percentage transmittance of 98.2. Refractive index of 1.32 of the nanoemulsion indicated the isotropic nature of the drug. Release rate of the drug from the nanoemulsion formulation was found to be quite significant (P < 0.001) as compared to the plain drug. In vivo oral bioavailability of the nanoemulsion formulation was found to be 2.6-fold higher than the plain drug (˜ 40%) as observed from pharmacokinetic studies. Thus it was observed that nanoemulsion proved itself as a promising alternate for improving the bioavailability of artemether.

Aggressive risk factor reduction study for atrial fibrillation and implications for the outcome of ablation: the ARREST-AF cohort study.

BACKGROUND: The long-term outcome of atrial fibrillation (AF) ablation demonstrates attrition. This outcome may be due to failure to attenuate the progressive substrate promoted by cardiovascular risk factors. OBJECTIVES: The goal of this study was to evaluate the impact of risk factor and weight management on AF ablation outcomes. METHODS: Of 281 consecutive patients undergoing AF ablation, 149 with a body mass index ≥27 kg/m(2) and ≥1 cardiac risk factor were offered risk factor management (RFM) according to American Heart Association/American College of Cardiology guidelines. After AF ablation, all 61 patients who opted for RFM and 88 control subjects were assessed every 3 to 6 months by clinic review and 7-day Holter monitoring. Changes in the Atrial Fibrillation Severity Scale scores were determined. RESULTS: There were no differences in baseline characteristics, number of procedures, or follow-up duration between the groups (p = NS). RFM resulted in greater reductions in weight (p = 0.002) and blood pressure (p = 0.006), and better glycemic control (p = 0.001) and lipid profiles (p = 0.01). At follow-up, AF frequency, duration, symptoms, and symptom severity decreased more in the RFM group compared with the control group (all p < 0.001). Single-procedure drug-unassisted arrhythmia-free survival was greater in RFM patients compared with control subjects (p < 0.001). Multiple-procedure arrhythmia-free survival was markedly better in RFM patients compared with control subjects (p < 0.001), with 16% and 42.4%, respectively, using antiarrhythmic drugs (p = 0.004). On multivariate analysis, type of AF (p < 0.001) and RFM (hazard ratio 4.8 [95% confidence interval: 2.04 to 11.4]; p < 0.001) were independent predictors of arrhythmia-free survival. CONCLUSIONS: Aggressive RFM improved the long-term success of AF ablation. This study underscores the importance of therapy directed at the primary promoters of the AF substrate to facilitate rhythm control strategies.

WITHDRAWN: An overview on stimuli responsive hydrogels as drug delivery system.

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