Early Discharge to Clinic-Based Therapy of Patients Presenting With Decompensated Heart Failure (EDICT-HF): Study Protocol for a Multi-Centre Randomised Controlled Trial.

BACKGROUND: Acute decompensated heart failure involves a high rate of mortality and complications. Management typically involves a multi-day hospital admission. However, patients often lose part of their function with each successive admission, and are at a high risk for hospital-associated complications such as nosocomial infection. This study aims to determine the safety and efficacy of the management of patients presenting with acute decompensated heart failure to clinic-based therapy vs usual inpatient care using a reproducible management pathway. METHOD: An investigator-initiated, prospective, non-inferiority, 1:1 randomised-controlled trial, stratified by left ventricular ejection fraction including 460 patients with a minimum follow-up of 7 days. This is a multi-centre study to be performed in centres across Victoria, Australia. Participants will be patients with either heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF), admitted for acute decompensation of heart failure. INTERVENTION: Early discharge to an outpatient-based Heart Failure Rapid Access Clinical Review (RACER) in addition to frequent medical/nursing at-home review for patients admitted with decompensated heart failure. RESULTS: The primary endpoint will be a non-inferiority assessment of re-hospitalisation at 30 days. Secondary outcomes include superiority assessment of hospitalisation at 30 days, a composite clinical endpoint of major adverse cardiac and cerebrovascular event (MACCE), hospital re-admission or mortality at 3 months, achievement of guideline-directed medical therapy, patient assessment of symptoms (visual-analogue scale quantified as area under curve and Kansas City Cardiomyopathy Questionnaire-12 [KCCQ-12]), attendance at 3-month outpatient follow-up, number of bed stays/clinics attended, proportion of patients free from congestion, change in serum creatinine level, treatment for electrolyte disturbances, time to transition from intravenous to oral diuretics, and health economics analysis (cost-benefit analysis, cost-utility analysis, incremental cost-effectiveness ratio). CONCLUSIONS: The Early Discharge to Clinic-Based Therapy of Patients Presenting with Decompensated Heart Failure (EDICT-HF) trial will help determine whether earlier discharge to out-of-hospital care is non-inferior to the usual practice of inpatient care, in patients with heart failure admitted to hospital for acute decompensation, as an alternative model of care.

The impact of age on ablation outcomes in AF-mediated cardiomyopathy.

INTRODUCTION: The absence of ventricular scar in patients with atrial fibrillation (AF) and systolic heart failure (HF) predicts left ventricular (LV) recovery following AF ablation. It is unknown whether age impacts the degree of LV recovery, reverse remodeling, or AF recurrence following catheter ablation (CA) among this population. OBJECTIVES: To evaluate the impact of age on LV recovery and AF recurrence in a population with AF and systolic HF without fibrosis (termed AF-mediated cardiomyopathy) following CA. METHODS: Consecutive patients undergoing CA between 2013 and 2021 with LV ejection fraction (LVEF) < 45% and absence of cardiac magnetic resonance imaging (CMR) detected LV myocardial fibrosis were stratified by age (<65 vs. ≥65 years). Following CA, participants underwent remote rhythm monitoring for 12 months with repeat CMR for HF surveillance. RESULTS: The study population consisted of 70 patients (10% female, mean LVEF 33 ± 9%), stratified into younger (age < 65 years, 63%) and older (age ≥ 65 years, 37%) cohorts. Baseline comorbidities, LVEF (34 ± 9 vs. 33 ± 8 ≥65 years, p = .686), atrial and ventricular dimensions (left atrial volume index: 55 ± 21 vs. 56 ± 14 mL/m2 age ≥ 65, p = .834; indexed left ventricular end-diastolic volume: 108 ± 40 vs. 104 ± 28 mL/m2 age ≥ 65, p = .681), pharmacotherapy and ablation strategy (pulmonary vein isolation in all; posterior wall isolation in 27% vs. 19% age ≥ 65, p = .448; cavotricuspid isthmus in 9% vs. 11.5% age ≥ 65) were comparable (all p > .05) albeit a higher CHADS2 VASc score in the older cohort (2.7 ± 0.9 vs. 1.6 ± 0.6 age < 65, p < .001).   Freedom from AF was comparable (hazard ratio: 0.65, 95% confidence interval: 0.38-1.48, LogRank p = .283) as was AF burden [0% (interquartile range, IQR: 0.0-2.1) vs. age ≥ 65: [0% (IQR 0.0-1.7), p = .516], irrespective of age. There was a significant improvement in LV systolic function in both groups (ΔLVEF + 21 ± 14% vs. +21 ± 12% age ≥ 65, p = .913), with LV recovery in the vast majority (73% vs. 69%, respectively, p = .759) at 13 (IQR: 12-16) months. This was accompanied by comparable improvements in functional status (New York Heart Association class p = .851; 6-min walk distance 50 ± 61 vs. 93 ± 134 m in age ≥ 65, p = .066), biomarkers (ΔN-terminal-pro brain natriuretic peptide -139 ± 246 vs. -168 ± 181 age ≥ 65,p = .629) and HF symptoms (Short Form-36 survey Δphysical component summary p = .483/Δmental component summary, p = .841). CONCLUSION: In patients undergoing CA for AF with systolic HF in the absence of ventricular scar, comparable improvements in ventricular function, symptoms, and freedom from AF are achieved irrespective of age.

Measurement of Stroke Volume With Echocardiography Compared to Gold Standard Cardiac Magnetic Resonance Imaging: An Observational Study.

OBJECTIVES: The authors aimed to compare the assessment of left ventricular (LV) stroke volume with transthoracic echocardiography (TTE) using 2- and 3-dimensional (2D and 3D) Doppler and volumetric techniques with gold standard cardiac magnetic resonance imaging (CMR). DESIGN: An observational study. SETTING: A medical research institute. PARTICIPANTS: A total of 187 volunteer participants free of known structural heart disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: LV stroke volume was measured with TTE using the following 4 techniques: LV outflow tract (LVOT) pulsed wave Doppler with 2D LVOT area, LVOT pulsed wave Doppler with 3D LVOT area, 2D volumetric (Simpson's biplane), and 3D volumetric techniques. This was compared with gold standard CMR. Stroke volume measured with echocardiography underestimated stroke volume compared to CMR by all techniques (p < 0.001 for all values compared to CMR). The LVOT Doppler stroke volume with a 3D area most closely agreed with CMR, with a bias of 6.35%. This bias progressively increased with 3D volumetric (13.4%), LVOT Doppler with a 2D area (15.1%), and 2D volumetric (18.3%) stroke volume techniques, with wider limits of agreement. CONCLUSION: Of the 4 echocardiographic LV stroke volume measurement methods the authors assessed, stroke volume with LVOT Doppler using 3D measurement of LVOT area most closely approximates gold standard CMR.

Cardioprotection Using Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy: 3-Year Results of the SUCCOUR Trial.

BACKGROUND: Global longitudinal strain (GLS) can predict cancer therapeutics-related cardiac dysfunction and guide initiation of cardioprotection (CPT). OBJECTIVES: In this study, the authors sought to determine whether echocardiography GLS-guided CPT provides less cardiac dysfunction in survivors of potentially cardiotoxic chemotherapy, compared with usual care at 3 years. METHODS: In this international multicenter prospective randomized controlled trial, patients were enrolled from 28 international sites. All patients treated with anthracyclines with another risk factor for heart failure were randomly allocated to GLS-guided (>12% relative reduction in GLS) or ejection fraction (EF)-guided (>10% absolute reduction of EF to <55%) CPT. The primary end point was the change in 3-dimensional (3D) EF (ΔEF) from baseline to 3 years. RESULTS: Among 331 patients enrolled, 255 (77%, age 54 ± 12 years, 95% women) completed 3-year follow-up (123 in the EF-guided group and 132 in the GLS-guided group). Most had breast cancer (n = 236; 93%), and anthracycline followed by trastuzumab was the most common chemotherapy regimen (84%). Although 67 (26%) had hypertension and 32 (13%) had diabetes mellitus, left ventricular function was normal at baseline (EF: 59% ± 6%, GLS: 20.7% ± 2.3%). CPT was administered in 18 patients (14.6%) in the EF-guided group and 41 (31%) in the GLS-guided group (P = 0.03). Most patients showed recovery in EF and GLS after chemotherapy; 3-year ΔEF was -0.03% ± 7.9% in the EF-guided group and -0.02% ± 6.5% in the GLS-guided (P = 0.99) group; respective 3-year EFs were 58% ± 6% and 59% ± 5% (P = 0.06). At 3 years, 17 patients (5%) had cancer therapeutics-related cardiac dysfunction (11 in the EF-guided group and 6 in the GLS guided group; P = 0.16); 1 patient in each group was admitted for heart failure. CONCLUSIONS: Among patients taking potentially cardiotoxic chemotherapy for cancer, the 3-year data showed improvement of LV dysfunction compared with 1 year, with no difference in ΔEF between GLS- and EF-guided CPT. (Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes [SUCCOUR]; ACTRN12614000341628).

Exercise for the Prevention of Anthracycline-Induced Functional Disability and Cardiac Dysfunction: The BREXIT Study.

BACKGROUND: Breast cancer survivors treated with anthracycline-based chemotherapy (AC) have increased risk of functional limitation and cardiac dysfunction. We conducted a 12-month randomized controlled trial in 104 patients with early-stage breast cancer scheduled for AC to determine whether 12 months of exercise training (ExT) could attenuate functional disability (primary end point), improve cardiorespiratory fitness (VO2peak), and prevent cardiac dysfunction. METHODS: Women 40 to 75 years of age with stage I to III breast cancer scheduled for AC were randomized to 3 to 4 days per week aerobic and resistance ExT for 12 months (n=52) or usual care (UC; n=52). Functional measures were performed at baseline, at 4 weeks after AC (4 months), and at 12 months, comprising: (1) cardiopulmonary exercise testing to quantify VO2peak and functional disability (VO2peak ≤18.0 mL·kg-1·min-1); (2) cardiac reserve (response from rest to peak exercise), quantified with exercise cardiac magnetic resonance measures to determine changes in left and right ventricular ejection fraction, cardiac output, and stroke volume; (3) standard-of-care echocardiography-derived resting left ventricular ejection fraction and global longitudinal strain; and (4) biochemistry (troponin and BNP [B-type natriuretic peptide]). RESULTS: Among 104 participants randomized, greater study attrition was observed among UC participants (P=0.031), with 93 women assessed at 4 months (ExT, n=49; UC, n=44) and 87 women assessed at 12 months (ExT, n=49; UC, n=38). ExT attenuated functional disability at 4 months (odds ratio, 0.32 [95% CI, 0.11-0.94]; P=0.03) but not at 12 months (odds ratio, 0.27 [95% CI, 0.06-1.12]; P=0.07). In a per-protocol analysis, functional disability was prevented entirely at 12 months among participants adherent to ExT (ExT, 0% versus UC, 20%; P=0.005). Compared with UC at 12 months, ExT was associated with a net 3.5-mL·kg-1·min-1 improvement in VO2peak that coincided with greater cardiac output, stroke volume, and left and right ventricular ejection fraction reserve (P<0.001 for all). There was no effect of ExT on resting measures of left ventricular function. Postchemotherapy troponin increased less in ExT than in UC (8-fold versus 16-fold increase; P=0.002). There were no changes in BNP in either group. CONCLUSIONS: In women with early-stage breast cancer undergoing AC, 12 months of ExT did not attenuate functional disability, but provided large, clinically meaningful benefits on VO2peak and cardiac reserve. REGISTRATION: URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12617001408370.

Diastolic flow in the left ventricular outflow tract - A normal physiological and underappreciated echocardiographic finding.

Purpose: Diastolic waveforms in the left ventricular outflow tract (LVOT) are commonly observed with Doppler echocardiography. The incidence and mechanism are not well described. Methods: This was a retrospective observational study of 186 adult patients, athletes and non-athletes, free of known cardiac disease, presenting for comprehensive transthoracic echocardiography at a research institute. We aimed to evaluate the incidence and echocardiographic associations between LVOT diastolic waveforms. Results: Left ventricular outflow tract early to mid-diastolic waveforms were present in 100% of athletes and 95% of non-athletes. The LVOT diastolic velocity time integral was larger in athletes than non-athletes with a mean 8.3 cm (95% CI (7.6-8.9)) vs. 5.1 cm (4.4-5.9) (P < 0.0001). Multivariate predictors of this diastolic waveform were age (P = 0.002), slower heart rate (P = 0.035), higher stroke volume (P = 0.003), large mitral E (P = 0.019) and higher E/e' (P = 0.015). Discussion: An LVOT early diastolic wave is a normal physiological finding. It is related to a flow vortex redirecting diastolic mitral inflow around anterior mitral valve leaflet into the LVOT. Conclusions: Early to mid-diastolic LVOT waves are present in almost all patients but more prominent in young athletes than non-athletes. Diastolic LVOT waves increase with younger age, slower heart rate, larger stroke volume and enhanced diastolic function.

Urinary Volatile Organic Compound Testing in Fast-Track Patients with Suspected Colorectal Cancer.

Colorectal symptoms are common but only infrequently represent serious pathology, including colorectal cancer (CRC). A large number of invasive tests are presently performed for reassurance. We investigated the feasibility of urinary volatile organic compound (VOC) testing as a potential triage tool in patients fast-tracked for assessment for possible CRC. A prospective, multi-center, observational feasibility study was performed across three sites. Patients referred to NHS fast-track pathways for potential CRC provided a urine sample that underwent Gas Chromatography-Mass Spectrometry (GC-MS), Field Asymmetric Ion Mobility Spectrometry (FAIMS), and Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) analysis. Patients underwent colonoscopy and/or CT colonography and were grouped as either CRC, adenomatous polyp(s), or controls to explore the diagnostic accuracy of VOC output data supported by an artificial neural network (ANN) model. 558 patients participated with 23 (4%) CRC diagnosed. 59% of colonoscopies and 86% of CT colonographies showed no abnormalities. Urinary VOC testing was feasible, acceptable to patients, and applicable within the clinical fast track pathway. GC-MS showed the highest clinical utility for CRC and polyp detection vs. controls (sensitivity = 0.878, specificity = 0.882, AUROC = 0.896) but it is labour intensive. Urinary VOC testing and analysis are feasible within NHS fast-track CRC pathways. Clinically meaningful differences between patients with cancer, polyps, or no pathology were identified suggesting VOC analysis may have future utility as a triage tool.

Investigation of urinary volatile organic compounds as novel diagnostic and surveillance biomarkers of bladder cancer.

BACKGROUND: The diagnosis and surveillance of urothelial bladder cancer (UBC) require cystoscopy. There is a need for biomarkers to reduce the frequency of cystoscopy in surveillance; urinary volatile organic compound (VOC) analysis could fulfil this role. This cross-sectional study compared the VOC profiles of patients with and without UBC, to investigate metabolomic signatures as biomarkers. METHODS: Urine samples were collected from haematuria clinic patients undergoing diagnostic cystoscopy and UBC patients undergoing surveillance. Urinary headspace sampling utilised solid-phase microextraction and VOC analysis applied gas chromatography-mass spectrometry; the output underwent metabolomic analysis. RESULTS: The median participant age was 70 years, 66.2% were male. Of the haematuria patients, 21 had a new UBC diagnosis, 125 had no cancer. In the surveillance group, 75 had recurrent UBC, 84 were recurrence-free. A distinctive VOC profile was observed in UBC patients compared with controls. Ten VOCs had statistically significant abundances useful to classify patients (false discovery rate range 1.9 × 10-7-2.8 × 10-2). Two prediction models were evaluated using internal validation. An eight-VOC diagnostic biomarker panel achieved AUROC 0.77 (sensitivity 0.71, specificity 0.72). A six-VOC surveillance biomarker panel obtained AUROC 0.80 (sensitivity 0.71 and specificity 0.80). CONCLUSIONS: Urinary VOC analysis could aid the diagnosis and surveillance of UBC.

Application of a solid-phase microextraction-gas chromatography-mass spectrometry/metal oxide sensor system for detection of antibiotic susceptibility in urinary tract infection-causing Escherichia coli - A proof of principle study.

PURPOSE: Antibiotic resistance is widespread throughout the world and represents a serious health concern. There is an urgent need for the development of novel tools for rapidly distinguishing antibiotic resistant bacteria from susceptible strains. Previous work has demonstrated that differences in antimicrobial susceptibility can be reflected in differences in the profile of volatile organic compounds (VOCs) produced by dissimilar strains. The aim of this study was to investigate the effect of the presence of cephalosporin antibiotics on the VOC profile of extended spectrum beta-lactamase (ESBL) and non-ESBL producing strains of Escherichia coli. MATERIAL AND METHODS: In this study, VOCs from strains of Escherichia coli positive and negative for the most commonly encountered ESBL, CTX-M in the presence of cephalosporin antibiotics were assessed using solid-phase microextraction (SPME) coupled with a combined gas chromatography-mass spectrometry/metal oxide sensor (GC-MS/MOS) system. RESULTS: Our proof-of-concept study allowed for distinguishing CTX-M positive and negative bacteria within 2 â€‹h after the addition of antibiotics. One MOS signal (RT: 22.6) showed a statistically significant three-way interaction (p â€‹= â€‹0.033) in addition to significant two-way interactions for culture and additive (p â€‹= â€‹0.046) plus time and additive (p â€‹= â€‹0.020). There were also significant effects observed for time (p â€‹= â€‹0.009), culture (p â€‹= â€‹0.030) and additive (p â€‹= â€‹0.028). No effects were observed in the MS data. CONCLUSIONS: The results of our study showed the potential of VOC analysis using SPME combined with a GC-MS/MOS system for the early detection of CTX-M-producing, antibiotic-resistant E. coli, responsible for urinary tract infections (UTIs).

Hyphenated Mass Spectrometry versus Real-Time Mass Spectrometry Techniques for the Detection of Volatile Compounds from the Human Body.

Mass spectrometry (MS) is an analytical technique that can be used for various applications in a number of scientific areas including environmental, security, forensic science, space exploration, agri-food, and numerous others. MS is also continuing to offer new insights into the proteomic and metabolomic fields. MS techniques are frequently used for the analysis of volatile compounds (VCs). The detection of VCs from human samples has the potential to aid in the diagnosis of diseases, in monitoring drug metabolites, and in providing insight into metabolic processes. The broad usage of MS has resulted in numerous variations of the technique being developed over the years, which can be divided into hyphenated and real-time MS techniques. Hyphenated chromatographic techniques coupled with MS offer unparalleled qualitative analysis and high accuracy and sensitivity, even when analysing complex matrices (breath, urine, stool, etc.). However, these benefits are traded for a significantly longer analysis time and a greater need for sample preparation and method development. On the other hand, real-time MS techniques offer highly sensitive quantitative data. Additionally, real-time techniques can provide results in a matter of minutes or even seconds, without altering the sample in any way. However, real-time MS can only offer tentative qualitative data and suffers from molecular weight overlap in complex matrices. This review compares hyphenated and real-time MS methods and provides examples of applications for each technique for the detection of VCs from humans.

A literature survey of all volatiles from healthy human breath and bodily fluids: the human volatilome.

This paper comprises an updated version of the 2014 review which reported 1846 volatile organic compounds (VOCs) identified from healthy humans. In total over 900 additional VOCs have been reported since the 2014 review and the VOCs from semen have been added. The numbers of VOCs found in breath and the other bodily fluids are: blood 379, breath 1488, faeces 443, milk 290, saliva 549, semen 196, skin 623 and urine 444. Compounds were assigned CAS registry numbers and named according to a common convention where possible. The compounds have been included in a single table with the source reference(s) for each VOC, an update on our 2014 paper. VOCs have also been grouped into tables according to their chemical class or functionality to permit easy comparison. Careful use of the database is needed, as a number of the identified VOCs only have level 2-putative assignment, and only a small fraction of the reported VOCs have been validated by standards. Some clear differences are observed, for instance, a lack of esters in urine with a high number in faeces and breath. However, the lack of compounds from matrices such a semen and milk compared to breath for example could be due to the techniques used or reflect the intensity of effort e.g. there are few publications on VOCs from milk and semen compared to a large number for breath. The large number of volatiles reported from skin is partly due to the methodologies used, e.g. by collecting skin sebum (with dissolved VOCs and semi VOCs) onto glass beads or cotton pads and then heating to a high temperature to desorb VOCs. All compounds have been included as reported (unless there was a clear discrepancy between name and chemical structure), but there may be some mistaken assignations arising from the original publications, particularly for isomers. It is the authors' intention that this work will not only be a useful database of VOCs listed in the literature but will stimulate further study of VOCs from healthy individuals; for example more work is required to confirm the identification of these VOCs adhering to the principles outlined in the metabolomics standards initiative. Establishing a list of volatiles emanating from healthy individuals and increased understanding of VOC metabolic pathways is an important step for differentiating between diseases using VOCs.

The Australia and New Zealand Cardio-Oncology Registry: evaluation of chemotherapy-related cardiotoxicity in a national cohort of paediatric cancer patients.

Cancer therapy related cardiac dysfunction (CTRCD) is an area of increasing focus, particularly during the survivorship period, for paediatric, adolescent and adult cancer survivors. With the advent of immunotherapy and targeted therapy, there is a new set of mechanisms from which paediatric and young adult patients with cancer may suffer cardiovascular injury. Furthermore, cardiovascular disease is the leading cause of morbidity and mortality in the survivorship period. The recently established Australian Cardio-Oncology Registry is the largest and only population-based cardiotoxicity database of paediatric and adolescent and young adult oncology patients in the world, and the first paediatric registry that will document cardiotoxicity caused by chemotherapy and novel targeted therapies using a prospective approach. The database is designed for comprehensive data collection and evaluation of the Australian practice in terms of diagnosis and management of CTRCD. Using the Australian Cardio-Oncology Registry critical clinical information will be collected regarding predisposing factors for the development of CTRCD, the rate of subclinical left ventricular dysfunction and transition to overt heart failure, further research into protectant molecules against cardiac dysfunction and aid in the discovery of which genetic variants predispose to CTRCD. A health economic arm of the study will assess the cost/benefit of both the registry and cardio-oncology clinical implementation. Finally, an imaging arm will establish if exercise cardiac magnetic resonance imaging and VO2 max testing is a more sensitive predictor of cardiac reserve in paediatric and adolescent and young adult oncology patients exposed to cardiac toxic therapies.

Can post-mortem coronary artery calcium scores aid diagnosis in young sudden death?

This study sought to explore the feasibility and utility of post-mortem coronary artery calcium (CAC) scoring in identifying patients with ischemic heart disease as cause of sudden death. 100 deceased patients aged 18-50 years underwent post-mortem examination in the setting of sudden death. At post-mortem, fifty cases were determined to have ischemic heart disease, and fifty had death attributed to trauma or unascertained causes. The CAC score was calculated in a blinded manner from post-mortem CTs performed on all cases. CAC scores were assessable in 97 non-decomposed cases (feasibility 97%). The median CAC score was 88 Agatston units [IQR 0-286] in patients deceased from ischemic heart disease vs 0 [IQR 0-0] in patients deceased from other causes (p < 0.0001). Presence of any coronary calcification differed significantly between ischemic heart disease and non-ischemic groups (adjusted odds ratio 10.7, 95% CI 3.2-35.5). All cases with a CAC score > 100 (n = 22) had ischemic heart disease as the cause of death. Fifteen cases had a CAC score of zero but severe coronary disease at post-mortem examination. Post-mortem CAC scoring is highly feasible. An elevated CAC score in cases 18-50 years old with sudden death predicts ischemic heart disease at post-mortem examination. However, a CAC score of zero does not exclude significant coronary artery disease. Post-mortem CAC score may be considered as a further assessment tool to help predict likely cause of death when there is an objection to or unavailability of post-mortem examination.

Catheter Ablation Versus Medication in Atrial Fibrillation and Systolic Dysfunction: Late Outcomes of CAMERA-MRI Study.

OBJECTIVES: This study sought to determine the long-term outcomes of restoring sinus rhythm with catheter ablation (CA). BACKGROUND: The CAMERA-MRI (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Heart Failure-An MRI-Guided Multicenter Randomized Controlled Trial) study demonstrated that restoration of sinus rhythm with CA significantly improved left ventricular ejection fraction (LVEF) compared with medical rate control (MRC) at 6 months in persistent atrial fibrillation and otherwise unexplained systolic heart failure. However, the long-term outcomes have not been reported. METHODS: Patients enrolled in the CAMERA-MRI study were followed for 4 years with echocardiogram and cardiac magnetic resonance. CA involved pulmonary vein isolation and posterior left atrial wall isolation in 94%. Patients crossed over to CA after 6-month study duration. Arrhythmia burden was determined with implanted cardiac monitors or cardiac devices. RESULTS: Sixty-six patients (age 62 ± 10 years, atrial fibrillation duration of 22 ± 16 months, and LVEF 33 ± 9%) were randomized 1:1 to CA versus MRC. Eighteen of 33 patients crossed over from MRC group to CA group. At 4.0 ± 0.9 years, atrial fibrillation recurred in 27 patients (57%) in the CA group with a mean burden of 10.6 ± 21.2% after 1.4 ± 0.6 procedures. There was an absolute increase in LVEF with CA of 16.4 ± 13.3% compared with 8.6 ± 7.6% in MRC (p = 0.001). In the CA group, the absence of ventricular late gadolinium enhancement was associated with a greater improvement in absolute LVEF (19 ± 13% vs. 10 ± 11% in the late gadolinium enhancement-positive group; p = 0.04) and LVEF normalization in 19 patients (58%) versus 4 patients (18%) in the late gadolinium enhancement-positive group (p = 0.008) at 4.0 ± 0.9 years follow-up. CONCLUSIONS: CA is superior to MRC in improving LVEF in the long term in patients with atrial fibrillation and systolic heart failure. The greatest recovery in systolic function was demonstrated in the absence of ventricular fibrosis on cardiac magnetic resonance.

Towards the Identification of Antibiotic-Resistant Bacteria Causing Urinary Tract Infections Using Volatile Organic Compounds Analysis-A Pilot Study.

Antibiotic resistance is an unprecedented threat to modern medicine. The analysis of volatile organic compounds (VOCs) from bacteria potentially offers a rapid way to determine antibiotic susceptibility in bacteria. This study aimed to find the optimal conditions to obtain the maximum number of VOCs detected which next allowed the assessment of differences in VOC profiles between susceptible and resistant isolates of Escherichia coli causing urinary tract infections. The analysis of VOCs in the headspace above the bacterial cultures allowed the distinguishing of resistant and susceptible bacteria based on the abundance of six VOCs with 85.7% overall accuracy. The results of this preliminary study are promising, and with development could lead to a practical, faster diagnostic method for use in routine microbiology.

An Optimization of Liquid-Liquid Extraction of Urinary Volatile and Semi-Volatile Compounds and Its Application for Gas Chromatography-Mass Spectrometry and Proton Nuclear Magnetic Resonance Spectroscopy.

Urinary volatile compounds (VCs) have been recently assessed for disease diagnoses. They belong to very diverse chemical classes, and they are characterized by different volatilities, polarities and concentrations, complicating their analysis via a single analytical procedure. There remains a need for better, lower-cost methods for VC biomarker discovery. Thus, there is a strong need for alternative methods, enabling the detection of a broader range of VCs. Therefore, the main aim of this study was to optimize a simple and reliable liquid-liquid extraction (LLE) procedure for the analysis of VCs in urine using gas chromatography-mass spectrometry (GC-MS), in order to obtain the maximum number of responses. Extraction parameters such as pH, type of solvent and ionic strength were optimized. Moreover, the same extracts were analyzed using Proton Nuclear Magnetic Resonance Spectroscopy (1H-NMR), to evaluate the applicability of a single urine extraction for multiplatform purposes. After the evaluation of experimental conditions, an LLE protocol using 2 mL of urine in the presence of 2 mL of 1 M sulfuric acid and sodium sulphate extracted with dichloromethane was found to be optimal. The optimized method was validated with the external standards and was found to be precise and linear, and allowed for detection of >400 peaks in a single run present in at least 50% of six samples-considerably more than the number of peaks detected by solid-phase microextracton fiber pre-concentration-GC-MS (328 ± 6 vs. 234 ± 4). 1H-NMR spectroscopy of the polar and non-polar extracts extended the range to >40 more (mainly low volatility compounds) metabolites (non-destructively), the majority of which were different from GC-MS. The more peaks detectable, the greater the opportunity of assessing a fingerprint of several compounds to aid biomarker discovery. In summary, we have successfully demonstrated the potential of LLE as a cheap and simple alternative for the analysis of VCs in urine, and for the first time the applicability of a single urine solvent extraction procedure for detecting a wide range of analytes using both GC-MS and 1H-NMR analysis to enhance putative biomarker detection. The proposed method will simplify the transport between laboratories and storage of samples, as compared to intact urine samples.

Breath analysis for detection of viral infection, the current position of the field.

The COVID-19 pandemic has highlighted the importance of rapid, cost effective, accurate, and non-invasive testing for viral infections. Volatile compounds (VCs) have been suggested for several decades as fulfilling these criteria. However currently very little work has been done in trying to diagnose viral infections using VCs. Much of the work carried out to date involves the differentiation of bacterial and viral sources of infection and often the detection of bacterial and viral co-infection. However, this has usually been done in vitro and very little work has involved the use of human participants. Viruses hijack the host cell metabolism and do not produce their own metabolites so identifying virus specific VCs is at best a challenging task. However, there are proteins and lipids that are potential candidates as markers of viral infection. The current understanding is that host cell glycolysis is upregulated under viral infection to increase the available energy for viral replication. There is some evidence that viral infection leads to the increase of production of fatty acids, alkanes, and alkanes related products. For instance, 2,3-butandione, aldehydes, 2,8-dimethyl-undecane and n-propyl acetate have all been correlated with viral infection. Currently, the literature points to markers of oxidative stress (e.g. nitric oxide, aldehydes etc) being the most useful in the determination of viral infection. The issue, however, is that there are also many other conditions that can lead to oxidative stress markers being produced. In this review a range of (mainly mass spectrometric) methods are discussed for viral detection in breath, including breath condensate. Currently MALDI-ToF-MS is likely to be the preferred method for the identification of viral strains and variants of those strains, however it is limited by its need for the viral strains to have been sequenced and logged in a database.

A mechanistic study and review of volatile products from peroxidation of unsaturated fatty acids: an aid to understanding the origins of volatile organic compounds from the human body.

The assessment of volatile compounds (VOCs) for disease diagnosis is a growing area of research. There is a need to provide hard evidence i.e. biochemical routes, to justify putative VOC biomarkers, as in many cases this remains uncertain, which weakens their authenticity. Recently reports of volatile hydrocarbons and or aldehydes in bodily fluids and breath have been attributed to oxidative stress, although as discussed here, fewer compounds have been reported than expected from a mechanistic examination. Oxidative stress can result from many disease states which produce inflammation, and a better understanding of the interconnection between oxidative stress and the release of VOCs from target diseased and healthy organs could greatly help diagnoses. It is generally considered that oxidation of unsaturated fatty acids are a major source of these VOCs. An investigation listing the many possible volatile oxidation products has not been undertaken. This is described here using a mechanistic analysis (based on the literature) of the compounds derived from molecular cleavage and the results compared with a recent review of all the VOCs emanating from the human body, which satisfactorily explains the presence of at least 100 VOCs. Six important unsaturated fatty acids, oleic, palmitoleic, linoleic, linolenic, arachidonic, and cervonic acids have been shown to be capable of producing up to 18 n+6 unique breakdown products (where n = the number of alkene double bonds in the fatty acid hydrocarbon chain), in total 299 compounds. In many cases these have not been reported. We suggest several reasons for this: these VOCs have not been expected, so researchers are not looking for them and importantly some are not present in the mass spectral libraries, or they are too low a concentration to have been detected, or are not present. Furthermore a theoretical explanation for the origins of branched aldehydes and other compounds arising from bacterial oxidative metabolism of unsaturated fatty acids are described.