Exposure to Caper Spurge (Euphorbia lathyris) Sap: A Case of Ocular and Periorbital Toxicity.

Introduction: We aimed to describe a case of bilateral keratoconjunctivitis after exposure to the toxic sap of Euphorbia lathyris. Case Report: A 76-year-old gentleman presented after exposure to E. lathyris whilst he was gardening. He had 6/12 visual acuity in his right eye, and 6/4 in his left. Examination revealed marked periocular dermatitis, conjunctival injection and corneal oedema in the right eye with diffuse punctate epithelial staining. He was treated with ocular irrigation, topical steroids, antibiotics, cycloplegics and lubricants. Over 48 h, his left eye started to become symptomatic. He developed bilateral corneal epithelial defects and anterior chamber inflammation. His visual acuity worsened to 6/36 right and 6/24 left. At his 3-week follow-up, there was marked improvement in the resolution of the toxic keratoconjunctivitis in both eyes. Conclusion: Toxic sap from E. lathyris can cause severe keratoconjunctivitis. Irrigation of both eyes despite unilateral symptoms and early follow-up should be considered signs of toxicity may only become evident after 24-48 h.

A Standardized Protocol of Simultaneous Transepithelial Phototherapeutic Keratectomy (PTK) Followed by Corneal Collagen Crosslinking for Keratoconus.

PURPOSE: To report outcomes in patients with progressive keratoconus who underwent a standardized protocol of transepithelial phototherapeutic keratectomy (t-PTK) laser followed by accelerated corneal collagen crosslinking (CXL). METHODS: All patients with progressive keratoconus undergoing our protocol at a London clinic between 2019 and 2023 were included. The protocol involved t-PTK at 58-µm central ablation depth at a 9-mm treatment zone on the Schwind Amaris 1050RS platform. Preoperative K readings of 43.0D (both K1 and K2) were inputted for all cases. Patients then underwent CXL with a pulsed-light accelerated protocol (30 mW/cm2 for 8 minutes of UVA exposure time with 1 second on/1 second off). RESULTS: Seventy-nine eyes from 55 patients were included with an average follow-up of 12 months (range 6-24 months). Both mean uncorrected distance visual acuity (UDVA) and best spectacle-corrected visual acuity improved significantly from 0.42 preoperatively to 0.29 postoperatively (P < 0.01) and 0.11 to 0.06 postoperatively (P < 0.01), respectively. The refractive cylinder reduced significantly from -3.07D to -2.63D (P < 0.05). The mean Km improved from 46.15D to 45.44D (P < 0.01) and mean Kmax from 54.03D to 52.52D (P < 0.01). 77% of eyes (n = 61) exhibited Kmax improvement postoperatively, and 56% showed an improvement in UDVA (n = 44). 16% (n = 13) had worsening of vision, but of these, only 1 patient had visual loss of more than 2 lines. No eyes had corneal haze reported at the final follow-up, and none required additional treatment. CONCLUSIONS: This standardized simultaneous t-PTK and CXL protocol is safe and effective for the treatment of progressive keratoconus, providing visual, refractive, and topographic improvements.

Fluctuating hypermetropia due to intraocular lens displacement caused by iris pigment epithelial cyst.

Purpose: To report a case of hyperopic shift following lens replacement surgery due to an enlarging iris pigment epithelial (IPE) cyst. Observations: A gentleman presented with reduced visual acuity (Snellen unaided 20/25) 12 months followed lens replacement surgery. Examination revealed a retro-pupillary iris lesion that appeared to be displacing the posterior chamber intraocular lens (IOL) and was causing a hyperopic shift (refraction +2.00). Anterior segment optical coherence tomography imaging confirmed this to be an IPE cyst with a posteriorly displaced IOL body. After observation over 30 months, the IPE cyst spontaneously reduced in size and the IOL returned to a more physiological position. Unaided visual acuity improved to Snellen 20/16 and refraction improved to +0.50. Conclusions and Importance: To our knowledge, an IPE cyst that shows growth following intraocular surgery has not previously been reported. This growth resulted in a hyperopic shift due to posterior displacement of the IOL. This case demonstrates spontaneous regression of the cyst, and suggests that over time these cysts can change in size.

Transepithelial phototherapeutic keratectomy for treatment-resistant recurrent corneal erosion syndrome.

BACKGROUND: To evaluate the efficacy and safety of trans-epithelial phototherapeutic keratectomy (TE-PTK) as a treatment for recurrent corneal erosion syndrome (RCES) in patients with symptoms refractory to conventional treatments. METHODS: All patients who received TE-PTK treatment for RCES had failed 3 or more conventional treatments and were reviewed, and if met criteria, approved by healthcare workers of the British Columbia public health authority (Medical Services Plan (MSP). A retrospective chart review and telephone survey were conducted at the Pacific Laser Eye Centre (PLEC). Exclusion criteria were ocular co-morbidities potentially affecting treatment efficacy. RESULTS: This study included 593 eyes of 555 patients (46.2% male; 50.9 ± 14.2 years old) who underwent TE-PTK. The leading identified causes of RCES were trauma (45.7%) and anterior basement membrane dystrophy (44.2%). The most common pre-PTK interventions were ocular lubricants (90.9%), hypertonic solutions (77.9%), and bandage contact lenses (50.9%). Thirty-six eyes had undergone surgical interventions such as stromal puncture, epithelial debridement, or diamond burr polishing. Post-PTK, 78% of patients did not require any subsequent therapies and 20% required ongoing drops. Six patients (1.1%) reported no symptom improvement and required repeat TE-PTK for ongoing RCES symptoms after initial TE-PTK. All 6 eyes were successfully retreated with TE-PTK (average time to retreatment was 11.3 ± 14.9 months). There was no significant difference in best corrected visual acuity pre- vs. post-operatively. The mean post-operative follow-up was 60.5 months (range: 5-127 months). CONCLUSION: TE-PTK has a good efficacy and safety profile for treatment-resistant RCES. The third-party public health-reviewed nature of this study, the low recurrence rate of RCES, and the low PTK retreatment rate suggest that TE-PTK might be considered for wider use in the management of RCES.

Local anaesthesia as a standard of care for penetrating keratoplasty?

BACKGROUND/OBJECTIVES: To determine preferences in the use of local anaesthesia (LA) versus general anaesthesia (GA) for penetrating keratoplasty (PK), and to examine the safety of LA for PK. SUBJECTS/METHODS: A retrospective analysis of PKs performed at an ophthalmology department in Canada from 01/01/2008 to 01/01/2020 was conducted to investigate rate of major complications. A questionnaire was also sent out to cornea specialists in the United Kingdom (UK) and Canada to determine trends in anaesthesia use for PK. Data on anaesthesia use in keratoplasty data was also obtained from the National Health Service Blood and Tissue (NHSBT) register. RESULTS: The retrospective study found that 2143 PKs were performed under LA by 4 surgeons. The following complications were revealed: 1 acute anxiety attack with tachycardia, 3 extraocular myotoxicity cases requiring squint surgery, 1 expulsive suprachoroidal haemorrhage and 1 retrobulbar haemorrhage. The survey revealed 92% of cornea specialists in Canada preferred LA to GA. In the UK, 4.5% of specialists preferred LA, with most preferring GA due to suprachoroidal haemorrhage risk. NHSBT data revealed that 86.6% of 6181 PKs performed in UK between 01/04/2015 and 31/03/2020 were done under GA. CONCLUSIONS: LA is preferred for PK in Canada, in contrast to the UK where GA is preferred. Our retrospective study suggests a low incidence of LA-related complications. We suggest that LA should be considered for most cornea transplant techniques, including optical penetrating keratoplasty. Rising worldwide keratoplasty numbers, ageing populations and risks of pandemics (e.g. COVID-19) give more reason for reduced reliance on GA.

Surgery for idiopathic epiretinal membrane.

BACKGROUND: Epiretinal membrane is an abnormal sheet of avascular fibrocellular tissue that develops on the inner surface of the retina. Epiretinal membrane can cause impairment of sight as a consequence of progressive distortion of retinal architecture. OBJECTIVES: To determine the effects of surgery compared to no intervention for epiretinal membrane. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, ISRCTN registry, US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). There were no restrictions to language or year of publication. The databases were last searched on 20 May 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) assessing surgical removal of idiopathic epiretinal membrane compared to placebo, no treatment or sham treatment. Paired or within-person studies were included, as well as those where both eyes of a single participant were treated. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane, and assessed certainty using the GRADE system. We considered the following five outcome measures: mean change in best corrected visual acuity (BCVA) in the study eye between baseline (before randomisation), 6 months and 12 months later; proportion of people with a gain of 0.3 logMAR or more of visual acuity in the study eye as measured by a logMAR chart at a starting distance of 4 m at 6 months and 12 months after randomisation; proportion of people with a loss of 0.3 logMAR or more of visual acuity in the study eye as measured by a logMAR chart at a starting distance of 4 m at 6 months and 12 months after randomisation; mean quality of life score at 6 months and 12 months following surgery, measured using a validated questionnaire; and any harm identified during follow-up. MAIN RESULTS: We included one study in the review. This was a RCT including 53 eyes of 53 participants with mild symptomatic epiretinal membrane and BCVA of 65 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Participants were randomly allocated to immediate surgery or to watchful waiting with deferred surgery if indicated by evidence of disease progression. The study was limited by imprecision owing to the small number of participants and was at some risk of bias owing to inconsistencies in the time points for outcome assessment and in the management of lens opacity. At 12 months, the visual acuity in the immediate surgery group was higher by a mean of 2.1 (95% confidence interval (CI) -2.0 to 6.2 ETDRS letters; 53 participants; low-certainty evidence) than the watchful waiting/deferred surgery group. The evidence of the effect of immediate surgery on gains of 0.3 logMAR or more of visual acuity is very uncertain (risk ratio (RR) 0.55, 95% CI 0.06 to 4.93; 53 participants; very low-certainty evidence). At 12 months, no participant in either group sustained a loss of 0.3 logMAR or more of visual acuity (53 participants; low-certainty evidence). The included study did not measure quality of life. At 12 months, no serious adverse event was identified in any participant. One participant developed chronic minimal cystoid macular oedema following immediate surgery (53 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: We found no RCT that directly investigated the effect of surgery compared to no intervention. For severe disabling epiretinal membrane, the lack of a RCT comparing surgery to no intervention may reflect evidence from non-randomised studies in favour of surgery; a RCT may be considered unnecessary and ethically unacceptable because a superior effect of surgery is widely accepted. For mild symptomatic epiretinal membrane, however, the value of surgery is uncertain. Low-certainty evidence from this review suggests that watchful waiting or deferred surgery may offer outcomes as favourable as immediate surgery. However, this finding needs to be confirmed in further RCTs with appropriate statistical power, masking of treatment allocation, consistent management of cataract, and measurement of outcomes including patient-reported quality of life over a more extended time frame.

Topography-Guided Photorefractive Keratectomy for Postkeratoplasty Astigmatism: Long-Term Outcomes.

PURPOSE: To evaluate the long-term efficacy and safety of topography-guided photorefractive keratectomy (TG-PRK) for postkeratoplasty refractive error correction. METHODS: A retrospective interventional case series of 54 eyes of 50 patients who underwent previous corneal transplants. Unaided distance visual acuity (UDVA) and best corrected visual acuity (CDVA), manifest refraction, mean central keratometric value, mean keratometric astigmatism, and postoperative complications were reviewed. RESULTS: Final follow-up was at mean 31 (±17) months. Sixteen point seven percent of eyes underwent more than 1 surface ablation. Mean UDVA improved from 0.96 ± 0.06 logarithm of the minimum angle of resolution (LogMAR) preoperatively to 0.46 ± 0.05 LogMAR of resolution at the final follow-up (Bonferroni, P < 0.0001). Mean UDVA improved by 4.4 Snellen lines. Improvement in CDVA was not significant, although a significant improvement was noted when eyes with preoperative CDVA <20/40 were analyzed separately (t test, P = 0.005). Mean astigmatism improved from -4.4 ± 0.26 D preoperatively to -2.4 ± 0.26 D at the final follow-up (Bonferroni, P < 0.0001), whereas mean SEQ improved from -2.5 ± 0.39 D preoperatively to -1.1 ± 0.25 D (Bonferroni, P = 0.02). In total, 9% at the preoperative visit and 55% at the final visit had less than 2 D of astigmatism, respectively. Keratometric astigmatism decreased from 5.24 ± 0.36 D preoperatively to 2.98 ± 0.34 D at the final follow-up (t test, P < 0.0001). No eyes developed clinically significant haze, 14.8% developed regression, and 13% had a reduction of 2 or more CDVA lines. CONCLUSIONS: Postkeratoplasty topography-guided photorefractive keratectomy has good long-term efficacy and safety, resulting in significant UDVA, refractive, and keratometric improvement. Regression can occur after the first year of treatment, emphasizing the importance of long-term follow-up.

An update on chemical eye burns.

Ocular chemical injuries vary in severity, with the more severe end of the spectrum having profound visual consequences and medicolegal implications. Grading of ocular injuries is critical for determining acute treatment and visual prognosis. Poor immediate management results in more challenging treatment of acute disease. Similarly, poorly controlled acute disease results in more treatment-resistant chronic ocular disease. Despite several decades of research and public health initiatives, simple and effective interventions such as wearing protective eyewear and immediate irrigation of eyes remain as key challenges. Education and prevention are therefore important public health messages. Hurdles in the acute management of disease include poor evidence-base for commonly used treatments (e.g. based on experimental animal studies), reduced treatment adherence rates and high clinic non-attendance rates. The evolution of treatment strategies, particularly limbal stem cell transplantation, has revolutionised the visual and cosmetic outcomes in chronic phases of disease. It is therefore increasingly important to consider tertiary referral for patients with limbal stem cell failure or vision-limiting corneal scarring.

Adherence to Treatment and Follow-Up in Patients with Severe Chemical Eye Burns.

INTRODUCTION: To investigate the demographics, acute management and compliance rates of severe chemical eye burn cases that presented to the largest eye hospital in the United Kingdom (UK). METHODS: All patients presenting to the Moorfields Eye Hospital emergency department are registered on the electronic patient administration system (PAS). A search of the PAS for patients assigned a preset diagnosis of 'chemical injury' was performed for the period from 1 January to 31 March 2016. The results of the PAS search and handwritten clerking notes were reviewed. Eyes that were found to have ≥ 33% limbal ischaemia or limbal staining, or corneal haze that obscured the details of the iris, were recorded as having severe chemical injuries. RESULTS: 55 patients had mild chemical eye burns, and 11 eyes of 10 patients had severe burns. Average patient age was 37 years (SD 22 years) and 22 years (SD 10 years) for mild and severe chemical injuries, respectively. 53% of the mild injuries and 90% of the severe injuries were in males. 7 (70%) of the 10 severe injuries were assault-related. In the severe chemical injuries group, first presentation to the emergency department was 24 h or more postinjury in 50% of the patients, 33% stopped ascorbate and citrate drops (ocular pain), 40% stopped attending clinical follow-up sessions, and 45% of the eyes had a final best corrected visual acuity (BCVA) of 6/18 or worse. CONCLUSION: A significant proportion of the severe ocular chemical burns were assault-related. Delayed presentation and poor treatment adherence and follow-up attendance rates are significant challenges in patients with severe chemical burns. Patient education and public health awareness are important strategies. These findings also raise the question of whether these patients, who are mostly young males, should be admitted to improve treatment adherence rates and visual outcome.

Intracameral Phenylephrine to Arrest Intraoperative Intraocular Bleeding: A New Technique.

Intraoperative intraocular bleeding can present a major challenge during anterior segment operations, such as cataract and glaucoma surgery. In the presence of significant intraocular bleeding, the surgeon may be unable to proceed if the bleeding cannot be controlled. Uncontrolled bleeding may also result in intraoperative or postoperative complications. Intracameral injection of phenylephrine was used in three consecutive cases of intraoperative anterior chamber bleeding during cataract surgery, one of which was combined with CyPass® Micro-Stent insertion. This resulted in complete cessation of bleeding within a minute of the injection. No further intraoperative or postoperative hemorrhage was seen. As far as we know, this is the first report of intracameral phenylephrine use intraoperatively to successfully stop anterior chamber bleeding, enabling safe completion of surgery.

Nerf gun eye injuries: traumatic hyphema.

Three unrelated patients attended the accident and emergency department with pain and blurred vision after ocular injury with a Nerf gun. Two were adults and one was a child, all of which presented within a 3 months' period. All three cases were found to have ≥1 mm of traumatic hyphema (pooling of blood in anterior chamber of the eye), indicating significant ocular trauma. The two adult patients had formed hyphema and uveitis. The 11-year-old child had formed hyphema, corneal oedema, anterior uveitis, localised angle recession and commotio retinae, which further highlight the severity of the ocular trauma. Significant Nerf gun ocular injuries are not reported in the literature, as far as we know. This case series serves to raise awareness of the seriousness of Nerf gun ocular injuries. It encourages further exploration of reasons for such injuries, as well as a review of protective measures against ocular trauma.

Non-amyloidogenic effects of α2 adrenergic agonists: implications for brimonidine-mediated neuroprotection.

The amyloid beta (Aß) pathway is strongly implicated in neurodegenerative conditions such as Alzheimer's disease and more recently, glaucoma. Here, we identify the α2 adrenergic receptor agonists (α2ARA) used to lower intraocular pressure can prevent retinal ganglion cell (RGC) death via the non-amyloidogenic Aß-pathway. Neuroprotective effects were confirmed in vivo and in vitro in different glaucoma-related models using α2ARAs brimonidine (BMD), clonidine (Clo) and dexmedetomidine. α2ARA treatment significantly reduced RGC apoptosis in experimental-glaucoma models by 97.7% and 92.8% (BMD, P<0.01) and 98% and 92.3% (Clo, P<0.01)) at 3 and 8 weeks, respectively. A reduction was seen in an experimental Aß-induced neurotoxicity model (67% BMD and 88.6% Clo, both P<0.01, respectively), and in vitro, where α2ARAs significantly (P<0.05) prevented cell death, under both hypoxic (CoCl2) and stress (UV) conditions. In experimental-glaucoma, BMD induced ninefold and 25-fold and 36-fold and fourfold reductions in Aß and amyloid precursor protein (APP) levels at 3 and 8 weeks, respectively, in the RGC layer, with similar results with Clo, and in vitro with all three α2ARAs. BMD significantly increased soluble APPα (sAPPα) levels at 3 and 8 weeks (2.1 and 1.6-fold) in vivo and in vitro with the CoCl2 and UV-light insults. Furthermore, treatment of UV-insulted cells with an sAPPα antibody significantly reduced cell viability compared with BMD-treated control (52%), co-treatment (33%) and untreated control (27%). Finally, we show that α2ARAs modulate levels of laminin and MMP-9 in RGCs, potentially linked to changes in Aß through APP processing. Together, these results provide new evidence that α2ARAs are neuroprotective through their effects on the Aß pathway and sAPPα, which to our knowledge, is the first description. Studies have identified the need for α-secretase activators and sAPPα-mimetics in neurodegeneration; α2ARAs, already clinically available, present a promising therapy, with applications not only to reducing RGC death in glaucoma but also other neurodegenerative processes involving Aß.

A semi-automated technique for labeling and counting of apoptosing retinal cells.

BACKGROUND: Retinal ganglion cell (RGC) loss is one of the earliest and most important cellular changes in glaucoma. The DARC (Detection of Apoptosing Retinal Cells) technology enables in vivo real-time non-invasive imaging of single apoptosing retinal cells in animal models of glaucoma and Alzheimer's disease. To date, apoptosing RGCs imaged using DARC have been counted manually. This is time-consuming, labour-intensive, vulnerable to bias, and has considerable inter- and intra-operator variability. RESULTS: A semi-automated algorithm was developed which enabled automated identification of apoptosing RGCs labeled with fluorescent Annexin-5 on DARC images. Automated analysis included a pre-processing stage involving local-luminance and local-contrast "gain control", a "blob analysis" step to differentiate between cells, vessels and noise, and a method to exclude non-cell structures using specific combined 'size' and 'aspect' ratio criteria. Apoptosing retinal cells were counted by 3 masked operators, generating 'Gold-standard' mean manual cell counts, and were also counted using the newly developed automated algorithm. Comparison between automated cell counts and the mean manual cell counts on 66 DARC images showed significant correlation between the two methods (Pearson's correlation coefficient 0.978 (p < 0.001), R Squared = 0.956. The Intraclass correlation coefficient was 0.986 (95% CI 0.977-0.991, p < 0.001), and Cronbach's alpha measure of consistency = 0.986, confirming excellent correlation and consistency. No significant difference (p = 0.922, 95% CI: -5.53 to 6.10) was detected between the cell counts of the two methods. CONCLUSIONS: The novel automated algorithm enabled accurate quantification of apoptosing RGCs that is highly comparable to manual counting, and appears to minimise operator-bias, whilst being both fast and reproducible. This may prove to be a valuable method of quantifying apoptosing retinal cells, with particular relevance to translation in the clinic, where a Phase I clinical trial of DARC in glaucoma patients is due to start shortly.

A novel method of assessing quality of postgraduate psychiatry training: experiences from a large training programme.

BACKGROUND: Most assessments of the quality of postgraduate training are based on anonymised questionnaires of trainees. We report a comprehensive assessment of the quality of training at a large postgraduate psychiatry training institute using non-anonymised face-to-face interviews with trainees and their trainers. METHODS: Two consultant psychiatrists interviewed 99 trainees and 109 trainers. Scoring of interview responses was determined by using a pre-defined criteria. Additional comments were recorded as free text. Interviews covered 13 domains, including: Clinical, teaching, research and management opportunities, clinical environment, clinical supervision, adequacy of job description, absence of bullying and job satisfaction. Multiple interview domain scores were combined, generating a 'Combined' score for each post. RESULTS: The interview response rate was 97% for trainers 88% for trainees. There was a significant correlation between trainee and trainer scores for the same interview domains (Pearson's r = 0.968, p< 0.001). Overall scores were significantly higher for specialist psychiatry posts as compared to general adult psychiatry posts (Two tailed t-test, p < 0.001, 95% CI: -0.398 to -0.132), and significantly higher for liaison psychiatry as compared to other specialist psychiatry posts (t-test: p = 0.038, 95% CI: -0.3901, -0.0118). Job satisfaction scores of year 1 to year 3 core trainees showed a significant increase with increasing seniority (Linear regression coefficient = 0.273, 95% CI: 0.033 to 0.513, ANOVA p= 0.026). CONCLUSIONS: This in-depth examination of the quality of training on a large psychiatry training programme successfully elicited strengths and weakness of our programme. Such an interview scheme could be easily implemented in smaller schemes and may well provide important information to allow for targeted improvement of training. Additionally, trends in quality of training and job satisfaction amongst various psychiatric specialities were identified; specifically speciality posts and liaison posts in psychiatry were revealed to be the most popular with trainees.

Khat: social habit or cultural burden? A survey and review.

The aim of this article was to investigate the psychological and socioeconomic ramifications of Khat on its users and their communities. A thorough literature review was undertaken and a questionnaire was distributed among a Somali community in South London. From the 62 individuals surveyed, 79% were born in Somalia and 15% in the United Kingdom. Participants were asked to answer specific questions about their Khat use, their attitudes toward Khat use, and its perceived effect on their communities. The harms of Khat use are numerous, although they are not well recognized by its users. Khat's legal status means that it is widely available. Measures to reconsider its legality should be considered given the harm on its users.

Effect of atrioventricular optimization on circulating N-terminal pro brain natriuretic peptide following cardiac resynchronization therapy.

AIMS: Following CRT, atrioventricular (AV) optimization is not routinely practised. To evaluate its clinical utility, we examined the effect of AV delay optimization on the prognostic biomarker NT-proBNP. METHODS AND RESULTS: We prospectively studied 72 patients (mean age 73 ± 12.5 years, 70.8% male, 55.6% ischaemic) undergoing iterative AV optimization. Patients were divided into those whose nominal setting appeared ideal and not changed (Group 1, n = 22) and those whose AV delay was optimized (Group 2, n = 50). All patients underwent NT-proBNP assessment prior to CRT, and pre- and a median 5 days post-optimization. Compared with Group 1, NT-proBNP fell significantly in Group 2 patients (median 474 pg/mL) following optimization (P = 0.00001). A significant change in filling pattern (defined as a change in AV delay >50 ms) was required in 30% of patients, and it was this subgroup that derived the greater reduction in NT-proBNP levels [-1407 pg/mL, interquartile range (IQR) -3042 to -346 pg/mL] compared with those requiring <50 ms AV delay change (-125 pg/mL, IQR -1038 to 6 pg/mL), P = 0.0011. The benefit of AV optimization was principally observed in reverse remodelling non-responders (median -2167 pg/mL, IQR -3042 to -305 pg/mL) and in patients with a pseudonormal or restrictive filling pattern (median -1407 pg/mL, IQR -2809 to -342 pg/mL), compared with those with more benign diastolic filling (median - 264 pg/mL, IQR -1038 to -21 pg/mL), P = 0.033. CONCLUSIONS: In one-third of patients, major filling pattern changes are achieved with AV optimization, associated with subsequent rapid falls in NT-proBNP. The greater the AV delay change, the larger the NT-proBNP fall, and non-responders and those with restrictive or pseudonormal filling despite CRT are most likely to benefit.

Obesity, inflammation and brachial artery flow-mediated dilatation: therapeutic targets in patients with microvascular angina (cardiac syndrome X).

BACKGROUND: The pathophysiology of microvascular angina (cardiac syndrome X, CSX), (effort-induced angina, a positive response to exercise stress testing and angiographically normal coronary arteries) has not been fully elucidated. Various pathogenic mechanisms have been proposed, amongst which coronary microvascular dysfunction features prominently. Management of patients with microvascular angina is often challenging as a substantial number of patients does not respond to conventional anti-anginal therapy. In this study, we sought to assess the association between brachial artery FMD, high-sensitive C-reactive protein (hs-CRP) and cardiovascular risk factors including obesity in patients with cardiac syndrome X. METHODS AND RESULTS: Thirty-four consecutive CSX patients (29 female, mean age 60 ± 9 years) were recruited from a specialised CSX clinic. Twelve asymptomatic subjects (10 female, mean age 51 ± 12 years) with comparable cardiovascular risk factor profile served as controls. All participants underwent standardized computer-assisted FMD measurements and assessment of hs-CRP concentrations at study entry. Body mass index (BMI), used as a general measure of obesity was calculated as weight (kilograms) divided by height (meters squared). Compared to controls, CSX patients had significantly higher hs-CRP concentrations (p = 0.003) and impaired FMD (p < 0.01). Moreover, among the CSX patients, a correlation between FMD and hs-CRP (r = -0.66, p < 0.01), FMD and BMI (r = 0.377, p = 0.028), and hs-CRP and BMI (r = -0.372, p = 0.030) was found. CONCLUSION: Impaired brachial artery FMD is significantly associated with elevated hs-CRP concentrations and BMI in patients with CSX. The results support the concept that low-grade inflammation and obesity may promote vascular dysfunction in these patients representing therapeutic targets for future research investigations.

Utility of high and standard right precordial leads during ajmaline testing for the diagnosis of Brugada syndrome.

AIMS: The authors sought to assess the value of the high right precordial leads (RPL) to detect the Type I Brugada ECG pattern in patients suspected of carrying Brugada syndrome (BrS). METHODS: Ajmaline testing using 15-lead ECGs was performed in 183 patients suspected of carrying BrS. Standard 12-lead ECG with V1-V3 recorded from the fourth intercostal space and an additional three leads placed over V1-V3 recorded from the third intercostal space were analysed. ECGs were analysed for a Type I ECG pattern in either the standard or high RPLs. RESULTS: Of the 183 tests, 31 (17%) were positive, and 152 were negative. In all positive studies, at least one high RPL became positive. In 13/31 (42%) cases, the Type I ECG pattern could be observed only in the high RPLs. Standard or high V3 were never positive before standard or high V1-V2. In seven patients, a Type I pattern was seen in one standard and one high RPL (vertical relationship). CONCLUSIONS: The high RPLs are more sensitive than the conventional 12-lead ECG alone and initial observations suggest that they remain specific for BrS, while standard and high lead V3 offer redundant data. A vertical relationship of type 1 patterns may have a similar diagnostic value to that of a horizontal pair.