Sex Differences in Outcomes of an Intensive Risk Factor Modification Program in Patients With Atrial Fibrillation.

BACKGROUND: The outcomes of atrial fibrillation (AF) seem to be variable between males and females. We therefore aimed to determine sex differences in weight loss, cardiorespiratory fitness gain, and recurrence and progression of AF following risk factor management. METHODS: Of 1415 consecutive patients referred for electrophysiology management of AF, 825 had a body mass index of ≥27 kg/m2; after exclusions, 355 (males, 234; females, 121) were offered risk factor management and participation in a tailored exercise program. RESULTS: Females were older than males (65.5±10.4 versus 62.5±10.6 years; P=0.013) with a higher body mass index (34.1±5.4 versus 32.6±4.1 kg/m2; P=0.003) and more commonly paroxysmal AF (67.8% versus 48.3%; P<0.001). There was no sex difference in clinic attendance (58.7% versus 60%; P=0.82), weight loss (P=0.86), fitness gain (P=0.44), or improvement in AF symptoms (P=0.35). Weight loss (≥10% compared with <10%) was associated with lower total AF recurrence in males (hazard ratio, 0.41 [95% CI, 0.23-0.73]) and females (hazard ratio, 0.41 [95% CI, 0.20-0.83]). Fitness gain (≥2 metabolic equivalents compared with <2 metabolic equivalents) was associated with lower total AF recurrence in females (hazard ratio, 0.13 [95% CI, 0.05-0.30]) but not in males (hazard ratio, 0.63 [95% CI, 0.38-1.04]; P=0.002). There was a trend toward more reversal from persistent to paroxysmal AF in males compared with females (21.8% versus 14.0%; P=0.079). CONCLUSIONS: Males and females with AF demonstrate a similar degree of weight loss and fitness gain through structured risk factor management. However, fitness had a much greater benefit for total arrhythmia recurrence in females compared with males, whereas there was a trend toward more AF reversal in males. REGISTRATION: URL: https://anzctr.org.au; Unique identifier: ACTRN12614001123639.

Catheter ablation for persistent atrial fibrillation: patterns of recurrence and impact on quality of life and health care utilisation.

BACKGROUND AND AIMS: Patterns of atrial fibrillation (AF) recurrence post catheter ablation for persistent AF are not well described. This study aimed to describe the pattern of AF recurrence seen following catheter ablation for persistent AF (PsAF) and the implications for healthcare utilisation and quality of life. METHODS: This was a post-hoc analysis of the CAPLA study, an international, multi-centre study that randomised patients with symptomatic PsAF to pulmonary vein isolation plus posterior wall isolation or pulmonary vein isolation alone. Patients underwent twice daily single lead ECG, implantable device monitoring or three monthly Holter monitoring. RESULTS: 154 of 333 (46.2%) patients (median age 67.3 years, 28% female) experienced AF recurrence at 12-month follow-up. Recurrence was paroxysmal in 97 (63%) patients and persistent in 57 (37%). Recurrence type did not differ between randomisation groups (p=0.508). Median AF burden was 27.4% in PsAF recurrence and 0.9% in paroxysmal AF (PAF) recurrence (p<0.001). Patients with PsAF recurrence had lower baseline left ventricular ejection fraction (PsAF 50% vs PAF 60%, p<0.001) and larger left atrial volume (PsAF 54.2±19.3 ml/m² vs PAF 44.8±11.6 ml/m², p=0.008). Healthcare utilisation was significantly higher in PsAF (45 patients [78.9%]) vs PAF recurrence (45 patients [46.4%], p<0.001) and lowest in those without recurrence (17 patients [9.5%], p<0.001). Patients without AF recurrence had greater improvements in quality of life as assessed by the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire (Δ33.3±25.2 points) compared to those with PAF (Δ24.0±25.0 points, p=0.012) or PsAF (Δ13.4±22.9 points, p<0.001) recurrence. CONCLUSIONS: AF recurrence is more often paroxysmal after catheter ablation for PsAF irrespective of ablation strategy. Recurrent PsAF was associated with higher AF burden, increased healthcare utilisation and antiarrhythmic drug use. The type of AF recurrence and AF burden may be considered important endpoints in clinical trials investigating ablation of PsAF.

Global LEADR pivotal trial results.

BACKGROUND: Implantable cardioverter-defibrillators last longer, and interest in reliable leads with targeted lead placement is growing. The OmniaSecure™ defibrillation lead is a novel small-diameter, catheter-delivered lead designed for targeted placement, based on the established SelectSecure SureScan MRI Model 3830 lumenless pacing lead platform. OBJECTIVE: This trial assessed safety and efficacy of the OmniaSecure defibrillation lead. METHODS: The worldwide LEADR pivotal clinical trial enrolled patients indicated for de novo implantation of a primary or secondary prevention implantable cardioverter-defibrillator/cardiac resynchronization therapy defibrillator, all of whom received the study lead. The primary efficacy end point was successful defibrillation at implantation per protocol. The primary safety end point was freedom from study lead-related major complications at 6 months. The primary efficacy and safety objectives were met if the lower bound of the 2-sided 95% credible interval was >88% and >90%, respectively. RESULTS: In total, 643 patients successfully received the study lead, and 505 patients have completed 12-month follow-up. The lead was placed in the desired right ventricular location in 99.5% of patients. Defibrillation testing at implantation was completed in 119 patients, with success in 97.5%. The Kaplan-Meier estimated freedom from study lead-related major complications was 97.1% at 6 and 12 months. The trial exceeded the primary efficacy and safety objective thresholds. There were zero study lead fractures and electrical performance was stable throughout the mean follow-up of 12.7 ± 4.8 months (mean ± SD). CONCLUSION: The OmniaSecure lead exceeded prespecified primary end point performance goals for safety and efficacy, demonstrating high defibrillation success and a low occurrence of lead-related major complications with zero lead fractures.

Heart Failure with Mildly Reduced Ejection Fraction-A Phenotype Waiting to Be Explored.

Heart failure (HF) presents a significant global health challenge recognised by frequent hospitalisation and high mortality rates. The assessment of left ventricular (LV) ejection fraction (EF) plays a crucial role in diagnosing and predicting outcomes in HF, leading to its classification into preserved (HFpEF), reduced (HFrEF), and mildly reduced (HFmrEF) EF. HFmrEF shares features of both HFrEF and HFpEF but also exhibits distinct characteristics. Despite advancements, managing HFmrEF remains challenging due to its diverse presentation. Large-scale studies are needed to identify the predictors of clinical outcomes and treatment responses. Utilising biomarkers for phenotyping holds the potential for discovering new treatment targets. Given the uncertainty surrounding optimal management, individualised approaches are imperative for HFmrEF patients. This chapter examines HFmrEF, discusses the rationale for its re-classification, and elucidates HFmrEF's key attributes. Furthermore, it provides a comprehensive review of current treatment strategies for HFmrEF patients.

2023 Cardiac Society of Australia and New Zealand Expert Position Statement on Catheter and Surgical Ablation for Atrial Fibrillation.

Catheter ablation for atrial fibrillation (AF) has increased exponentially in many developed countries, including Australia and New Zealand. This Expert Position Statement on Catheter and Surgical Ablation for Atrial Fibrillation from the Cardiac Society of Australia and New Zealand (CSANZ) recognises healthcare factors, expertise and expenditure relevant to the Australian and New Zealand healthcare environments including considerations of potential implications for First Nations Peoples. The statement is cognisant of international advice but tailored to local conditions and populations, and is intended to be used by electrophysiologists, cardiologists and general physicians across all disciplines caring for patients with AF. They are also intended to provide guidance to healthcare facilities seeking to establish or maintain catheter ablation for AF.

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.

Utility of a guiding catheter for conduction system pacing: An early multicenter experience.

Background: Conduction system pacing (CSP), either as His bundle pacing (HBP) or as left bundle branch area pacing (LBBAP), may be superior to right ventricular apical or septal pacing. Objective: The study sought to present acute results for a new guiding catheter (Biotronik Selectra 3D) designed for CSP implantations of a retractable screw-in lead (Biotronik Solia S). Methods: The primary endpoint of the prospective, international nonrandomized BIO|MASTER.Selectra 3D study was freedom from catheter-related serious adverse device effects (SADEs) within 1 week of lead implantation. Results: Of 157 enrolled patients, CSP was achieved in 147 (93.6%) patients. No SADEs occurred within 7 days. LBBAP was achieved in 82 patients (45 as crossover from an HBP attempt) and HBP in 65 (44.2%) patients. In centers considering both HBP and LBBAP, the CSP implantation success approached 99%. Successful CSP implantations lasted on average ∼50 minutes (fluoroscopy ∼6 minutes). Most procedures (87.9%) needed only 1 catheter, even after switch from HBP to LBBAP. The catheter's handling was rated largely positive. In patients without bundle branch block, mean QRS duration increased from 106 ms (intrinsic) to 122 ms (CSP) (P = .001). In patients with bundle branch block, mean QRS duration decreased from 151 ms (intrinsic) to 137 ms (CSP) (P = .004). Conclusion: The Selectra 3D catheter is a valuable tool for HBP and LBBAP implantations of the stylet-supported pacemaker leads. When implanters considered both HBP and LBBAP, the success rate was ∼99%. Flexibility to change between different approaches may be advisable in heterogeneous and challenging areas, such as CSP implantations.

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.

Trends of Private Drugs' Sales and Costs Incurred by Patients on Anti-tuberculosis Drugs in Selected Districts of Jharkhand (2022): Results From Sub-national TB-Free Certification.

BACKGROUND: The government of India is committed to eliminating tuberculosis (TB) by 2025 under the National Tuberculosis Elimination Programme which provides free investigations and treatment as well as incentives for nutritional support during their treatment course. Many TB patients prefer to seek treatment from the private sector which sometimes leads to financial constraints for the patients. Our study aims to find the burden of TB patients in the private sector and the expenses borne by them for their treatment. METHODOLOGY: Sales data of rifampicin-containing formulation drug consumption in the private sector of six districts of Jharkhand was collected from Clearing and Forwarding agencies. Based on the drug sales data, the total incurring costs of the drugs, total number of patients, and cost per patient seeking treatment from the private sector were calculated for the year 2015-2021. ANOVA and the post hoc test (Tukey honestly significant difference (HSD)) were applied for analysis. RESULTS:  There was a marked difference amongst all the districts in relation to all the variables namely total costs, cost per patient, and total private patients seeking treatment from the private sector which was statistically significant (p < 0.001). East Singhbhum had the highest out-of-pocket expense and private patients as compared to all six districts. Lohardaga showed the sharpest decline in total private patients from 2015 to 2021. The average cost borne by private patients in 2015 was INR 1821 (95% CI 1086 - 2556) which decreased to INR 1033 (95% CI 507 - 1559) in 2021. CONCLUSION: From the study, it was concluded that the purchase of medicines for TB treatment from the private sector is one of the essential elements in out-of-pocket expenditure (OOPE) borne by TB patients. Hence, newer initiatives should be explored to foresee the future OOPE borne by the patients and decrease OOPE-induced poverty.

2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure.

Cardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing-induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre-procedure evaluation and preparation, implant procedure management, follow-up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

Posterior Wall Isolation Improves Outcomes for Persistent AF With Rapid Posterior Wall Activity: CAPLA Substudy.

BACKGROUND: Pulmonary vein isolation (PVI) is less effective in persistent atrial fibrillation (PerAF) than in paroxysmal atrial fibrillation (AF). However, the CAPLA (Effect of Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation: The CAPLA randomized clinical trial) of PVI vs posterior wall isolation (PWI) did not support empiric PWI in PerAF. We examined pulmonary vein (PV) and posterior wall (PW) electrical characteristics to determine if select patients may benefit from additional PWI. OBJECTIVES: This study sought to determine the impact of PV and PW electrical characteristics on AF ablation outcomes in the CAPLA randomized study. METHODS: Participants in spontaneous AF at the time of ablation were included from the CAPLA study. The mean, shortest, and longest PV, PW, and left atrial (LA) appendage cycle length measurements were annotated preablation using a multipolar catheter for 100 consecutive cycles. Next, cardioversion was performed with a high-density LA voltage map completed. Cox proportional hazards regression was utilized to determine clinical and electroanatomic predictors of AF recurrence overall and according to ablation strategy. Follow-up included twice daily single-lead electrocardiograms or continuous monitoring for 12 months. RESULTS: A total of 151 patients (27% female, age 65 ± 9 years, 18% long-standing PerAF, LA volume index 52 ± 16 mL/m2, median AF duration 5 months [IQR: 2-10 months]) were in AF on the day of procedure and were randomized to PVI alone (50%) or PVI+PWI (50%) according to the CAPLA randomized clinical trial protocol. Baseline clinical, echocardiographic, and electroanatomic parameters were comparable between groups (all P > 0.05) including PV and PW characteristics. After 12 months, freedom from AF off antiarrhythmic drug therapy was 51.7% in PVI and 49.7% in PVI+PWI (log-rank P = 0.564). Rapid PW activity was defined as less than the median of the shortest PW cycle length (140 ms) and rapid PV activity was defined as less than the median of the shortest PV cycle length (126 ms). In those with rapid PW activity, the addition of PWI was associated with greater arrhythmia-free survival (56.4%) vs PVI alone (38.6%) (HR: 0.78; 95% CI: 0.67-0.94; log-rank P = 0.030). Moreover, in those undergoing PVI only, the risk of AF recurrence was higher in those with rapid PW activity (55.3% vs 46.5% in slower PW activity; HR: 1.50, 95%CI 1.11-2.26; log-rank P = 0.036). Rapid PV activity and PV cycle length (individual PVs or average of all 4 PVs) were not associated with outcome (all P > 0.05) regardless of ablation strategy. There was no correlation between PW cycle length and posterior low voltage (r = -0.06, P = 0.496). The addition of PWI did not improve arrhythmia-free survival in subgroups with LA enlargement (LA volume index >34 mL/m2) (HR: 0.69; 95% CI: 0.39-1.25; P = 0.301), posterior low-voltage zone (HR: 1.06; 95% CI: 0.68-1.66; P = 0.807), or long-standing PerAF (HR: 1.10; 95% CI: 0.71-1.72; P = 0.669). CONCLUSIONS: Rapid PW activity is associated with an increased risk of AF recurrence post-catheter ablation. The addition of PWI in this subgroup was associated with a significant improvement in freedom from AF compared with PVI alone. The presence of rapid PW activity may identify patients with PerAF likely to benefit from PWI.

The Role of Posterior Wall Isolation in Catheter Ablation for Persistent Atrial Fibrillation and Systolic Heart Failure: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Catheter ablation for patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) is associated with improved left ventricular ejection fraction (LVEF) and survival compared with medical therapy. Nonrandomized studies have reported improved success with posterior wall isolation (PWI). Objective: To determine the impact of pulmonary vein isolation (PVI) with PWI vs PVI alone on outcomes in patients with HFrEF. Design, Setting, and Participants: This was an ad hoc secondary analysis of the CAPLA trial, a multicenter, prospective, randomized control trial that involved 11 centers in 3 countries (Australia, Canada, and UK). CAPLA featured 338 patients with persistent AF randomized to either PVI plusPWI or PVI alone. This substudy included patients in the original CAPLA study who had symptomatic HFrEF (LVEF <50% and New York Heart Association class ≥II). Interventions: Pulmonary vein isolation with PWI vs PVI alone. Main Outcomes and Measures: The primary end point was freedom from any documented atrial arrhythmia greater than 30 seconds, after a single ablation procedure, without the use of antiarrhythmic drug (AAD) therapy at 12 months. Results: A total of 98 patients with persistent AF and symptomatic HFrEF were identified (mean [SD] age, 62.1 [9.8] years; 79.5% men; and mean [SD] LVEF at baseline, 34.6% [7.9%]). After 12 months, 58.7% of patients with PVI plus PWI were free from recurrent atrial arrhythmia without the use of AAD therapy vs 61.5% with PVI alone (hazard ratio, 1.02; 95% CI, 0.54-1.91; P = .96). There were no significant differences in freedom from atrial arrhythmia with or without AAD therapy after multiple procedures (PVI plus PWI vs PVI alone, 60.9% vs 65.4%; P = .73) or AF burden (median, 0% in both groups; P = .78). Mean LVEF improved substantially in PVI plus PWI (∆ LVEF, 19.3% [13.0%; P < .01) and PVI alone (18.2% [14.1%; P < .01), with no difference between groups (P = .71). Normalization of LV function occurred in 65.2% of patients in the PVI plus PWI group and 50.0% of patients with PVI alone (P = .13). Conclusions and Relevance: The results of this study indicate that addition of PWI to PVI did not improve freedom from arrhythmia recurrence or recovery of LVEF in patients with persistent AF and symptomatic HFrEF. Catheter ablation was associated with significant improvements in systolic function, irrespective of ablation strategy used. These results caution against the routine inclusion of PWI in patients with HFrEF undergoing first-time catheter ablation for persistent AF. Trial Registration: http://anzctr.org.au Identifier: ACTRN12616001436460.

Nutritional supplementation to prevent tuberculosis incidence in household contacts of patients with pulmonary tuberculosis in India (RATIONS): a field-based, open-label, cluster-randomised, controlled trial.

BACKGROUND: In India, tuberculosis and undernutrition are syndemics with a high burden of tuberculosis coexisting with a high burden of undernutrition in patients and in the population. The aim of this study was to determine the effect of nutritional supplementation on tuberculosis incidence in household contacts of adults with microbiologically confirmed pulmonary tuberculosis. METHODS: In this field-based, open-label, cluster-randomised controlled trial, we enrolled household contacts of 2800 patients with microbiologically confirmed pulmonary tuberculosis across 28 tuberculosis units of the National Tuberculosis Elimination Programme in four districts of Jharkhand, India. The tuberculosis units were randomly allocated 1:1 by block randomisation to the control group or the intervention group, by a statistician using computer-generated random numbers. Although microbiologically confirmed pulmonary tuberculosis patients in both groups received food rations (1200 kcal, 52 grams of protein per day with micronutrients) for 6 months, only household contacts in the intervention group received monthly food rations and micronutrients (750 kcal, 23 grams of protein per day with micronutrients). After screening all household contacts for co-prevalent tuberculosis at baseline, all participants were followed up actively until July 31, 2022, for the primary outcome of incident tuberculosis (all forms). The ascertainment of the outcome was by independent medical staff in health services. We used Cox proportional hazards model and Poisson regression via the generalised estimating equation approach to estimate unadjusted hazard ratios, adjusted hazard ratios (aHRs), and incidence rate ratios (IRRs). This study is registered with CTRI-India, CTRI/2019/08/020490. FINDINGS: Between Aug 16, 2019, and Jan 31, 2021, there were 10 345 household contacts, of whom 5328 (94·8%) of 5621 household contacts in the intervention group and 4283 (90·7%) of 4724 household contacts in the control group completed the primary outcome assessment. Almost two-thirds of the population belonged to Indigenous communities (eg, Santhals, Ho, Munda, Oraon, and Bhumij) and 34% (3543 of 10 345) had undernutrition. We detected 31 (0·3%) of 10 345 household contact patients with co-prevalent tuberculosis disease in both groups at baseline and 218 (2·1%) people were diagnosed with incident tuberculosis (all forms) over 21 869 person-years of follow-up, with 122 of 218 incident cases in the control group (2·6% [122 of 4712 contacts at risk], 95% CI 2·2-3·1; incidence rate 1·27 per 100 person-years) and 96 incident cases in the intervention group (1·7% [96 of 5602], 1·4-2·1; 0·78 per 100 person-years), of whom 152 (69·7%) of 218 were patients with microbiologically confirmed pulmonary tuberculosis. Tuberculosis incidence (all forms) in the intervention group had an adjusted IRR of 0·61 (95% CI 0·43-0·85; aHR 0·59 [0·42-0·83]), with an even greater decline in incidence of microbiologically confirmed pulmonary tuberculosis (0·52 [0·35-0·79]; 0·51 [0·34-0·78]). This translates into a relative reduction of tuberculosis incidence of 39% (all forms) to 48% (microbiologically confirmed pulmonary tuberculosis) in the intervention group. An estimated 30 households (111 household contacts) would need to be provided nutritional supplementation to prevent one incident tuberculosis. INTERPRETATION: To our knowledge, this is the first randomised trial looking at the effect of nutritional support on tuberculosis incidence in household contacts, whereby the nutritional intervention was associated with substantial (39-48%) reduction in tuberculosis incidence in the household during 2 years of follow-up. This biosocial intervention can accelerate reduction in tuberculosis incidence in countries or communities with a tuberculosis and undernutrition syndemic. FUNDING: Indian Council of Medical Research-India TB Research Consortium.

Nutritional support for adult patients with microbiologically confirmed pulmonary tuberculosis: outcomes in a programmatic cohort nested within the RATIONS trial in Jharkhand, India.

BACKGROUND: Undernutrition is a common comorbidity of tuberculosis in countries with a high tuberculosis burden, such as India. RATIONS is a field-based, cluster-randomised controlled trial evaluating the effect of providing nutritional support to household contacts of adult patients with microbiologically confirmed pulmonary tuberculosis in Jharkhand, India, on tuberculosis incidence. The patient cohort in both groups of the trial was provided with nutritional support. In this study, we assessed the effects of nutritional support on tuberculosis mortality, treatment success, and other outcomes in the RATIONS patient cohort. METHODS: We enrolled patients (aged 18 years or older) with microbiologically confirmed pulmonary tuberculosis across 28 tuberculosis units. Patients received nutritional support in the form of food rations (1200 kcal and 52 g of protein per day) and micronutrient pills. Nutritional support was for 6 months for drug-susceptible tuberculosis and 12 months for multidrug-resistant tuberculosis; patients with drug-susceptible tuberculosis could receive an extension of up to 6 months if their BMI was less than 18·5 kg/m2 at the end of treatment. We recorded BMI, diabetes status, and modified Eastern Cooperative Oncology Group (ECOG) performance status at baseline. Clinical outcomes (treatment success, tuberculosis mortality, loss to follow-up, and change in performance status) and weight gain were recorded at 6 months. We assessed the predictors of tuberculosis mortality with Poisson and Cox regression using adjusted incidence rate ratios (IRRs) and adjusted hazard ratios (HRs). The RATIONS trial is registered with the Clinical Trials Registry of India (CTRI/2019/08/020490). FINDINGS: Between Aug 16, 2019, and Jan 31, 2021, 2800 patients (mean age 41·5 years [SD 14·5]; 1979 [70·7%] men and 821 [29·3%] women) were enrolled. At enrolment, 2291 (82·4%) patients were underweight (BMI <18·5 kg/m2), and 480 (17·3%) had a BMI of less than 14 kg/m2. The mean weight and BMI were 42·6 kg (SD 7·8) and 16·4 kg/m2 (2·6) in men and 36·1 kg (7·3) and 16·2 kg/m2 (2·9) in women. During the 6-month follow-up, treatment was successful in 2623 (93·7%) patients, 108 (3·9%) tuberculosis deaths occurred, 28 (1·0%) patients were lost to follow-up, and treatment failure was experienced by five (0·2%) patients. The median weight gain was 4·6 kg (IQR 2·8-6·8), but 1441 (54·8%) of 2630 patients remained underweight. At 2 months, 1444 (54·0%) of 2676 patients gained at least 5% of baseline weight. Baseline weight (adjusted IRR 0·95, 95% CI 0·90-0·99), BMI (0·88, 0·76-1·01), poor performance status (ECOG categories 3-4; 5·33, 2·90-9·79), diabetes (3·30, 1·65-6·72), and haemoglobin (0·85, 0·71-1·00) were predictors of tuberculosis mortality. A reduced hazard of death (adjusted HR 0·39, 95% CI 0·18-0·86) was associated with a 5% weight gain at 2 months. INTERPRETATION: In this study, nutritional support was provided to a cohort with a high prevalence of severe undernutrition. Weight gain, particularly in the first 2 months, was associated with a substantially decreased hazard of tuberculosis mortality. Nutritional support needs to be an integral component of patient-centred care to improve treatment outcomes in such settings. FUNDING: India Tuberculosis Research Consortium, Indian Council of Medical Research.

Theoretical Appraisal of Cyclopropenone: Aggregation and Complexes with Water.

Cyclopropenone (HCCOCH, "CPN") is an exotic quasi-aromatic cyclic carbene that abounds in the interstellar medium (ISM). Astronomical observations suggest that (i) stagnate CPN exhibits a tendency to polymerize and that (ii) interactions may occur between CPN and water that is also ubiquitous in the ISM. In this light, density functional theory investigations reveal cooperative hydrogen bonding, which leads to stable polymeric conformations of (CPN)n, tracked up to n = 14. Stable agglomerations with water, however, constitute at best only two CPN and two water molecules, signifying that while CPN exhibits remarkable cooperativity for "cohesive" clustering via hydrogen bonding, this tendency is markedly diminished for "hetero"-interactions. Multifaceted data are employed to probe cogent molecular descriptors, such as structure and energetics of various conformers, vibrational spectroscopic response, molecular electrostatic potential (MESP), effective atomic charges: all these, in unison, describe the evolution of the characteristics upon cluster formation. Salient stretching frequency shifts, as well as charge redistribution gleaned from MESP morphology, have a direct bearing on variegated hydrogen bonding patterns: linear, nonlinear, as well as bifurcated. In particular, characteristic C-H, C═O stretching, and O-H vibrations in the water complexes reveal a "softening" (downshift) of frequencies. While small conformers have markedly distinct MESP variations, the differences become less pronounced with incremental clustering, an effect substantiated by corresponding emergent atomic charges.

2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure.

Cardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing-induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre-procedure evaluation and preparation, implant procedure management, follow-up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

Correlation of myocardial strain by CMR-feature tracking with substrate abnormalities detected by electro-anatomical mapping in patients with nonischemic cardiomyopathy.

BACKGROUND: Late gadolinium enhancement (LGE) detected by cardiac MRI (CMR) has low correlation with low voltage zones (LVZs) detected by electroanatomical mapping (EAM). We aim to study correlation of myocardial strain by CMR- Feature Tracking (FT) alongside LGE with LVZs detected by EAM. METHODS: Nineteen consecutive CMRs of patients with EAM were analyzed offline by CMR-FT. Peak value of circumferential strain (CS), longitudinal strain (LS), and LGE was measured in each segment of the left ventricle (17-segment model). The percentage of myocardial segments with CS and LS > -17% was determined. Percentage area of LGE-scar was calculated. Global and segment-wise bipolar and unipolar voltage was collected. Percentage area of bipolar LVZ (<1.5 mV) and unipolar LVZ (<8.3 mV) was calculated. RESULTS: Mean age was 62±11 years. Mean LVEF was 37±13%. Mean global CS was -11.8±5%. Mean global LS was -11.2±4%. LGE-scar was noted in 74% of the patients. Mean percentage area of LGE-scar was 5%. There was significant correlation between percentage abnormality detected by LS with percentage bipolar LVZ (r = +0.5, p = 0.03) and combined percentage CS+LS abnormality with percentage unipolar LVZ (r = +0.5, p = 0.02). Per-unit increase in CS increased the percentage area of unipolar LVZ by 2.09 (p = 0.07) and per-unit increase in LS increased the percentage area of unipolar LVZ by 2.49 (p = 0.06). The concordance rates between CS and LS to localize segments with bipolar/unipolar LVZ were 79% and 95% compared to 63% with LGE. CONCLUSIONS: Myocardial strain detected by CMR-FT has a better correlation with electrical low voltage zones than the conventional LGE.