Importance of operator training and rest perfusion on the diagnostic accuracy of stress perfusion cardiovascular magnetic resonance.

BACKGROUND: Clinical evaluation of stress perfusion cardiovascular magnetic resonance (CMR) is currently based on visual assessment and has shown high diagnostic accuracy in previous clinical trials, when performed by expert readers or core laboratories. However, these results may not be generalizable to clinical practice, particularly when less experienced readers are concerned. Other factors, such as the level of training, the extent of ischemia, and image quality could affect the diagnostic accuracy. Moreover, the role of rest images has not been clarified. The aim of this study was to assess the diagnostic accuracy of visual assessment for operators with different levels of training and the additional value of rest perfusion imaging, and to compare visual assessment and automated quantitative analysis in the assessment of coronary artery disease (CAD). METHODS: We evaluated 53 patients with known or suspected CAD referred for stress-perfusion CMR. Nine operators (equally divided in 3 levels of competency) blindly reviewed each case twice with a 2-week interval, in a randomised order, with and without rest images. Semi-automated Fermi deconvolution was used for quantitative analysis and estimation of myocardial perfusion reserve as the ratio of stress to rest perfusion estimates. RESULTS: Level-3 operators correctly identified significant CAD in 83.6% of the cases. This percentage dropped to 65.7% for Level-2 operators and to 55.7% for Level-1 operators (p < 0.001). Quantitative analysis correctly identified CAD in 86.3% of the cases and was non-inferior to expert readers (p = 0.56). When rest images were available, a significantly higher level of confidence was reported (p = 0.022), but no significant differences in diagnostic accuracy were measured (p = 0.34). CONCLUSIONS: Our study demonstrates that the level of training is the main determinant of the diagnostic accuracy in the identification of CAD. Level-3 operators performed at levels comparable with the results from clinical trials. Rest images did not significantly improve diagnostic accuracy, but contributed to higher confidence in the results. Automated quantitative analysis performed similarly to level-3 operators. This is of increasing relevance as recent technical advances in image reconstruction and analysis techniques are likely to permit the clinical translation of robust and fully automated quantitative analysis into routine clinical practice.

Chronic subthreshold subdural cortical stimulation for the treatment of focal epilepsy originating from eloquent cortex.

Medically refractory epilepsy remains a major medical problem worldwide. Although some patients are eligible for surgical resection of seizure foci, a proportion of patients are ineligible for a variety of reasons. One such reason is that the foci reside in eloquent cortex of the brain and therefore resection would result in significant morbidity. This retrospective study reports our experience with a novel neurostimulation technique for the treatment of these patients. We identified three patients who were ineligible for surgical resection of the intracranially identified seizure focus because it resided in eloquent cortex, who underwent therapeutic trial of focal cortical stimulation delivered through the subdural monitoring grid. All three patients had a significant reduction in seizures, and two went on to permanent implantation, which resulted in long-term reduction in seizure frequency. In conclusion, this small case report provides some evidence of proof of concept of the role of targeted continuous neocortical neurostimulation in the treatment of medically refractory focal epilepsy, and provides support for ongoing investigations into this treatment modality.

Prevalence of myocardial crypts in a large retrospective cohort study by cardiovascular magnetic resonance.

BACKGROUND: Myocardial crypts are discrete clefts or fissures in otherwise compacted myocardium of the left ventricle (LV). Recent reports suggest a higher prevalence of crypts in patients with hypertrophic cardiomyopathy (HCM) and also within small samples of genotype positive but phenotype negative relatives. The presence of a crypt has been suggested to be a predictor of gene carrier status. However, the prevalence and clinical significance of crypts in the general population is unclear. We aimed to determine the prevalence of myocardial crypts in a large cohort of subjects using clinical cardiovascular magnetic resonance (CMR). METHODS: Consecutive subjects referred for clinical CMR during a 12-month period (n = 1020, age 52.6 ± 17, males: 61%) were included. Crypts were defined as >50% invagination into normal myocardium and their overall prevalence, location and shape was investigated and compared between different patient groups. RESULTS: The overall prevalence of crypts was 64/1020 (6.3%). In a predefined 'normal' control group the prevalence was lower (11/306, 3.6%, p = 0.031), but were equally prevalent in ischemic heart disease (12/236, 5.1%, p = n/s) and the combined non-ischemic cardiomyopathy (NICM) groups (24/373; 6.4%, p = n/s). Within the NICM group, crypts were significantly more common in HCM (9/76, 11.7%, p = 0.04) and hypertensive CM subjects (3/11, 27%, p = 0.03). In patients referred for CMR for family screening of inherited forms of CM, crypts were significantly more prevalent (10/41, 23%, p < 0.001), including a smaller group with a first degree relative with HCM (3/9, 33%, p = 0.01). CONCLUSION: Myocardial crypts are relatively common in the normal population, and increasingly common in HCM and hypertensive cardiomyopathy. Crypts are also more frequently seen in normal phenotype subjects referred because of a family history of an inherited cardiomyopathy and HCM specifically. It is uncertain what the significance of crypts are in this group, and because of variability in the imaging protocols used and their relative frequency within the normal population, should not be used to clinically stratify these patients. Prospective studies are required to confirm the clinical significance of myocardial crypts, as their significance remains unclear.

Reference values for healthy human myocardium using a T1 mapping methodology: results from the International T1 Multicenter cardiovascular magnetic resonance study.

BACKGROUND: T1 mapping is a robust and highly reproducible application to quantify myocardial relaxation of longitudinal magnetisation. Available T1 mapping methods are presently site and vendor specific, with variable accuracy and precision of T1 values between the systems and sequences. We assessed the transferability of a T1 mapping method and determined the reference values of healthy human myocardium in a multicenter setting. METHODS: Healthy subjects (n=102; mean age 41 years (range 17-83), male, n=53 (52%)), with no previous medical history, and normotensive low risk subjects (n=113) referred for clinical cardiovascular magnetic resonance (CMR) were examined. Further inclusion criteria for all were absence of regular medication and subsequently normal findings of routine CMR. All subjects underwent T1 mapping using a uniform imaging set-up (modified Look- Locker inversion recovery, MOLLI, using scheme 3(3)3(3)5)) on 1.5 Tesla (T) and 3 T Philips scanners. Native T1-maps were acquired in a single midventricular short axis slice and repeated 20 minutes following gadobutrol. Reference values were obtained for native T1 and gadolinium-based partition coefficients, λ and extracellular volume fraction (ECV) in a core lab using standardized postprocessing. RESULTS: In healthy controls, mean native T1 values were 950±21 msec at 1.5 T and 1052±23 at 3 T. λ and ECV values were 0.44±0.06 and 0.25±0.04 at 1.5 T, and 0.44±0.07 and 0.26±0.04 at 3 T, respectively. There were no significant differences between healthy controls and low risk subjects in routine CMR parameters and T1 values. The entire cohort showed no correlation between age, gender and native T1. Cross-center comparisons of mean values showed no significant difference for any of the T1 indices at any field strength. There were considerable regional differences in segmental T1 values. λ and ECV were found to be dose dependent. There was excellent inter- and intraobserver reproducibility for measurement of native septal T1. CONCLUSION: We show transferability for a unifying T1 mapping methodology in a multicenter setting. We provide reference ranges for T1 values in healthy human myocardium, which can be applied across participating sites.

Neuronal intranuclear inclusion disease in New Zealand: A novel discovery.

Neuronal intranuclear inclusion disease, caused by a GGC repeat expansion in the 5'-untranslated region of NOTCH2NLC, is a rare neurodegenerative condition with highly variable clinical manifestations. In recent years, the number of reported cases have increased dramatically in East Asia. We report the first four genetically confirmed cases of neuronal intranuclear inclusion disease in New Zealand, all having Polynesian ancestry (three New Zealand Maori and one Cook Island Maori). Phenotypically, they resemble cases reported from recent large East Asian cohorts.

Modelling accessibility of adult neurology care in Australia, 2020-2034.

Introduction: In 2015/2016, annual national expenditure on neurological conditions exceeded $A3 billion. However, a comprehensive study of the Australian neurological workforce and supply/demand dynamics has not previously been undertaken. Methods: Current neurological workforce was defined using neurologist survey and other sources. Workforce supply modelling used ordinary differential equations to simulate neurologist influx and attrition. Demand for neurology care was estimated by reference to literature regarding incidence and prevalence of selected conditions. Differences in supply versus demand for neurological workforce were calculated. Potential interventions to increase workforce were simulated and effects on supply versus demand estimated. Results: Modelling of the workforce from 2020 to 2034 predicted an increase in neurologist number from 620 to 89. We estimated a 2034 capacity of 638 024 Initial and 1 269 112 Review encounters annually, and deficits against demand estimated as 197 137 and 881 755, respectively. These deficits were proportionately greater in regional Australia, which has 31% of Australia's population (Australian Bureau of Statistics) but is served by only 4.1% of its neurologists as determined by our 2020 survey of Australia and New Zealand Association of Neurologists members. Nationally, simulated additions to the neurology workforce had some effect on the review encounter supply deficit (37.4%), but in Regional Australia, this impact was only 17.2%. Interpretation: Modelling of the neurologist workforce in Australia for 2020-2034 demonstrates a significant shortfall of supply relative to current and projected demand. Interventions to increase neurologist workforce may attenuate this shortfall but will not eliminate it. Thus, additional interventions are needed, including improved efficiency and additional use of support staff.

Convergent ablation for persistent atrial fibrillation: outcomes from a single-centre real-world experience.

OBJECTIVES: Atrial fibrillation (AF) is common and can cause significant morbidity and detriment to quality of life. Success rates for conventional catheter ablation are suboptimal in persistent AF (PsAF), especially when longstanding. Convergent hybrid ablation combines endoscopic surgical epicardial and endocardial catheter ablation. It offers promise in treating PsAF. We aimed to evaluate outcomes at our centre following convergent ablation. METHODS: We conducted an observational study of patients undergoing ablation from 2012 to 2019 at a London cardiac centre. Sixty-seven patients underwent convergent ablation entailing epicardial ablation, mostly via sub-xiphoid access, followed by endocardial left atrial catheter ablation. Baseline and follow-up data were obtained retrospectively from clinical records. Primary outcome was freedom from AF on/off anti-arrhythmic drugs after 12-month follow-up. Secondary outcomes included freedom from AF over the entire follow-up, freedom from anti-arrhythmic drugs, freedom from atrial arrhythmias, symptom status, repeat ablation and complications. RESULTS: At baseline, 80.6% had PsAF >1 year (80.6%), 49.3% had body mass index >30 kg/m2 at baseline and 19.4% had left ventricular ejection fraction of 40% or less. The median follow-up was 2.3 (1.4-3.7) years. Freedom from AF recurrence was 81.3% at 1 year and 61.5% over overall follow-up. Eleven patients (16.4%) required redo AF ablation. Prolonged AF duration was associated with increased recurrence at 12 months and duration >5 years with a shorter time to recurrence on Kaplan-Meier analysis, but this and other factors did not significantly impact the AF recurrence during the overall follow-up period. CONCLUSIONS: Convergent ablation had good 1-year and overall success rates for treating PsAF. Our results in a diverse, real-world population support the potential of convergent ablation in patients with challenging to treat PsAF.

Time-Averaged Wavefront Analysis Demonstrates Preferential Pathways of Atrial Fibrillation, Predicting Pulmonary Vein Isolation Acute Response.

Electrical activation during atrial fibrillation (AF) appears chaotic and disorganised, which impedes characterisation of the underlying substrate and treatment planning. While globally chaotic, there may be local preferential activation pathways that represent potential ablation targets. This study aimed to identify preferential activation pathways during AF and predict the acute ablation response when these are targeted by pulmonary vein isolation (PVI). In patients with persistent AF (n = 14), simultaneous biatrial contact mapping with basket catheters was performed pre-ablation and following each ablation strategy (PVI, roof, and mitral lines). Unipolar wavefront activation directions were averaged over 10 s to identify preferential activation pathways. Clinical cases were classified as responders or non-responders to PVI during the procedure. Clinical data were augmented with a virtual cohort of 100 models. In AF pre-ablation, pathways originated from the pulmonary vein (PV) antra in PVI responders (7/7) but not in PVI non-responders (6/6). We proposed a novel index that measured activation waves from the PV antra into the atrial body. This index was significantly higher in PVI responders than non-responders (clinical: 16.3 vs. 3.7%, p = 0.04; simulated: 21.1 vs. 14.1%, p = 0.02). Overall, this novel technique and proof of concept study demonstrated that preferential activation pathways exist during AF. Targeting patient-specific activation pathways that flowed from the PV antra to the left atrial body using PVI resulted in AF termination during the procedure. These PV activation flow pathways may correspond to the presence of drivers in the PV regions.

Cardiac stereotactic ablative radiotherapy for control of refractory ventricular tachycardia: initial UK multicentre experience.

BACKGROUND: Options for patients with ventricular tachycardia (VT) refractory to antiarrhythmic drugs and/or catheter ablation remain limited. Stereotactic radiotherapy has been described as a novel treatment option. METHODS: Seven patients with recurrent refractory VT, deemed high risk for either first time or redo invasive catheter ablation, were treated across three UK centres with non-invasive cardiac stereotactic ablative radiotherapy (SABR). Prior catheter ablation data and non-invasive mapping were combined with cross-sectional imaging to generate radiotherapy plans with aim to deliver a single 25 Gy treatment. Shared planning and treatment guidelines and prospective peer review were used. RESULTS: Acute suppression of VT was seen in all seven patients. For five patients with at least 6 months follow-up, overall reduction in VT burden was 85%. No high-grade radiotherapy treatment-related side effects were documented. Three deaths (two early, one late) occurred due to heart failure. CONCLUSIONS: Cardiac SABR showed reasonable VT suppression in a high-risk population where conventional treatment had failed.

Evaluation of the reentry vulnerability index to predict ventricular tachycardia circuits using high-density contact mapping.

BACKGROUND: Identifying arrhythmogenic sites to improve ventricular tachycardia (VT) ablation outcomes remains unresolved. The reentry vulnerability index (RVI) combines activation and repolarization timings to identify sites critical for reentrant arrhythmia initiation without inducing VT. OBJECTIVE: The purpose of this study was to provide the first assessment of RVI's capability to identify VT sites of origin using high-density contact mapping and comparison with other activation-repolarization markers of functional substrate. METHODS: Eighteen VT ablation patients (16 male; 72% ischemic) were studied. Unipolar electrograms were recorded during ventricular pacing and analyzed offline. Activation time (AT), activation-recovery interval (ARI), and repolarization time (RT) were measured. Vulnerability to reentry was mapped based on RVI and spatial distribution of AT, ARI, and RT. The distance from sites identified as vulnerable to reentry to the VT site of origin was measured, with distances <10 mm and >20 mm indicating accurate and inaccurate localization, respectively. RESULTS: The origins of 18 VTs (6 entrainment, 12 pace-mapping) were identified. RVI maps included 1012 (408-2098) (median, 1st-3rd quartiles) points per patient. RVI accurately localized 72.2% VT sites of origin, with median distance of 5.1 (3.2-10.1) mm. Inaccurate localization was significantly less frequent for RVI than AT (5.6% vs 33.3%; odds ratio 0.12; P = .035). Compared to RVI, distance to VT sites of origin was significantly larger for sites showing prolonged RT and ARI and were nonsignificantly larger for sites showing highest AT and ARI gradients. CONCLUSION: RVI identifies vulnerable regions closest to VT sites of origin. Activation-repolarization metrics may improve VT substrate delineation and inform novel ablation strategies.

Mortality in adult intensive care patients with severe systemic inflammatory response syndromes is strongly associated with the hypo-immune TNF -238A polymorphism.

The systemic inflammatory response syndrome (SIRS) is associated with activation of innate immunity. We studied the association between mortality and measures of disease severity in the intensive care unit (ICU) and functional polymorphisms in genes coding for Toll-like receptor 4 (TLR4), macrophage migratory inhibitory factor (MIF), tumour necrosis factor (TNF) and lymphotoxin-alpha (LTA). Two hundred thirty-three patients with severe SIRS were recruited from one general adult ICU in a tertiary centre in the UK. DNA from patients underwent genotyping by 5' nuclease assay. Genotype was compared to phenotype. Primary outcome was mortality in ICU. Minor allele frequencies were TLR4 +896G 7%, MIF 173C 16%, TNF -238A 10% and LTA +252G 34%. The frequency of the hypoimmune minor allele TNF -238A was significantly higher in patients who died in ICU compared to those who survived (p = 0.0063) as was the frequency of the two haplotypes LTA +252G, TNF -1031T, TNF -308G, TNF -238A and LTA +252G, TNF-1031T, TNF-308A and TNF-238A (p = 0.0120 and 0.0098, respectively). These findings re-enforce the view that a balanced inflammatory/anti-inflammatory response is the most important determinant of outcome in sepsis. Genotypes that either favour inflammation or its counter-regulatory anti-inflammatory response are likely to influence mortality and morbidity.

Caseous Intracardiac Calcification: A Diagnostic Enigma.

Intramyocardial calcification is a rare phenomenon often only discovered on postmortem. We describe the case of a healthy 69-year-old lady diagnosed with idiopathic caseous intracardiac calcification extending from the mitral valve annulus. We present high-quality images and propose an investigatory template for future cases.

Left ventricular activation-recovery interval variability predicts spontaneous ventricular tachyarrhythmia in patients with heart failure.

BACKGROUND: Enhanced beat-to-beat variability of repolarization is strongly linked to arrhythmogenesis and is largely due to variation in ventricular action potential duration (APD). Previous studies in humans have relied on QT interval measurements; however, a direct relationship between beat-to-beat variability of APD and arrhythmogenesis in humans has yet to be demonstrated. OBJECTIVE: This study aimed to explore the beat-to-beat repolarization dynamics in patients with heart failure at the level of ventricular APD. METHODS: Forty-three patients with heart failure and implanted cardiac resynchronization therapy - defibrillator devices were studied. Activation-recovery intervals as a surrogate for APD were recorded from the left ventricular epicardial lead while pacing from the right ventricular lead to maintain a constant cycle length. RESULTS: During a mean follow-up of 23.6±13.6 months, 11 patients sustained ventricular fibrillation/ventricular tachycardia (VT/VF) and received appropriate implantable cardioverter-defibrillator therapies (antitachycardia pacing or shock therapy). Activation-recovery interval variability (ARIV) was significantly greater in patients with subsequent VT/VF than in those without VT/VF (3.55±1.3 ms vs 2.77±1.09 ms; P=.047). Receiver operating characteristic curve analysis (area under the curve 0.71; P=.046) suggested high- and low-risk ARIV groups for VT/VF. Kaplan-Meier survival analysis demonstrated that the time until first appropriate therapy for VT/VF was significantly shorter in the high-risk ARIV group (P=.028). ARIV was a predictor for VT/VF in the multivariate Cox model (hazard ratio 1.623; 95% confidence interval 1.1-2.393; P=.015). CONCLUSION: Increased left ventricular ARIV is associated with an increased risk of VT/VF in patients with heart failure.

Unraveling the Underlying Arrhythmia Mechanism in Persistent Atrial Fibrillation: Results From the STARLIGHT Study.

BACKGROUND: The mechanisms that initiate and sustain persistent atrial fibrillation are not well characterized. Ablation results remain significantly worse than in paroxysmal atrial fibrillation in which the mechanism is better understood and subsequent targeted therapy has been developed. The aim of this study was to characterize and quantify patterns of activation during atrial fibrillation using contact mapping. METHODS: Patients with persistent atrial fibrillation (n=14; mean age, 61±8 years; ejection fraction, 59±10%) underwent simultaneous biatrial contact mapping with 64 electrode catheters. The atrial electrograms were transformed into phase, and subsequent spatiotemporal mapping was performed to identify phase singularities (PSs). RESULTS: PSs were located in both atria, but we observed more PSs in the left atrium compared with the right atrium (779±302, 552±235; P=0.015). Although some PSs of duration sufficient to complete >1 rotation were detected, the maximum PS duration was only 1150 ms, and the vast majority (97%) of PSs persisted for too short a period to complete a full rotation. Although in selected patients there was evidence of PS local clustering, overall, PSs were distributed globally throughout both chambers with no clear anatomic predisposition. In a subset of patients (n=7), analysis was repeated using an alternative established atrial PS mapping technique, which confirmed our initial findings. CONCLUSIONS: No sustained rotors or localized drivers were detected, and instead, the mechanism of arrhythmia maintenance was consistent with the multiple wavelet hypothesis, with passive activation of short-lived rotational activity. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01765075.

Comparison of MOLLI, shMOLLLI, and SASHA in discrimination between health and disease and relationship with histologically derived collagen volume fraction.

Aims: To determine the bioequivalence of several T1 mapping sequences in myocardial characterization of diffuse myocardial fibrosis. Methods and results: We performed an intra-individual sequence comparison of three types of T1 mapping sequences [MOdified Look-Locker Inversion recovery (MOLLI), Shortened MOdified Look-Locker Inversion recovery ((sh)MOLLI), and SAturation recovery single-SHot Acquisition (SASHA)]. We employed two model diseases of diffuse interstitial fibrosis [patients with non-ischaemic dilated cardiomyopathy (NIDCM), n = 32] and aortic stenosis [(AS), n = 25)]. Twenty-six healthy individuals served as controls. Relationship with collagen volume fraction (CVF) was assessed using endomyocardial biopsies (EMB) intraoperatively in 12 AS patients. T2 mapping (GraSE) was also performed. Myocardial native T1 with MOLLI and shMOLLI showed, firstly, an excellent discriminatory accuracy between health and disease [area under the curves (P-value): 0.94 (0.88-0.99); 0.87 (0.79-0.94); 0.61 (0.49-0.72)], secondly, relationship between histological CVF [native T1 MOLLI vs. shMOLLI vs. SASHA: r = 0.582 (P = 0.027), r = 0.524 (P = 0.046), r = 0.443 (P = 0.150)], and thirdly, with native T2 [r = 0.628(P < 0.001), r = 0.459 (P = 0.003), r = 0.211 (P = 0.083)]. The respective relationships for extracellular volume fraction with CVF [r = 0.489 (P = 0.044), r = 0.417 (0.071), r = 0.353 (P = 0.287)] were significant for MOLLI, but not other sequences. In AS patients, native T2 was significantly higher compared to controls, and associated with levels of C-reactive protein and troponin. Conclusion: T1 mapping sequences differ in their bioequivalence for discrimination between health and disease as well as associations with diffuse myocardial fibrosis.

How to achieve ultrasound-guided femoral venous access: the new standard of care in the electrophysiology laboratory.

PURPOSE: Bedside vascular ultrasound machines are increasingly available. They are used to facilitate safer vascular access across a number of different specialties. In the electrophysiology laboratory however, where patients are frequently anticoagulated and require the insertion of multiple venous sheaths, anatomical landmark techniques predominate. Despite the high number of vascular complications associated with electrophysiological procedures and the increasing evidence to support its use in electrophysiology, ultrasound remains underutilised. A new standard of care is required. A comprehensive technical report, providing a detailed explanation of this important technique, will provide other electrophysiology centres with the knowledge and justification for adopting ultrasound guidance as their standard practice. METHOD: We review the increasing body of evidence which demonstrates that routine ultrasound usage can substantially improve the safety of femoral venous access in the electrophysiology laboratory. We offer a comprehensive technical report to guide operators through the process of ultrasound-guided venous access, with a specific focus on the electrophysiology laboratory. Additionally, we detail a novel technique which utilises real-time colour Doppler ultrasound to accurately identify needle tip location during venous puncture. CONCLUSIONS: The use of vascular ultrasound to guide femoral venous cannulation is rapid, inexpensive and easily learnt. Ultrasound is readily available and offers the potential to significantly reduce vascular complications in the unique setting of the electrophysiology laboratory. Ultrasound guidance to achieve femoral venous access should be the new standard of care in electrophysiology.