Disruptive CHD8 mutations define a subtype of autism early in development.

Autism spectrum disorder (ASD) is a heterogeneous disease in which efforts to define subtypes behaviorally have met with limited success. Hypothesizing that genetically based subtype identification may prove more productive, we resequenced the ASD-associated gene CHD8 in 3,730 children with developmental delay or ASD. We identified a total of 15 independent mutations; no truncating events were identified in 8,792 controls, including 2,289 unaffected siblings. In addition to a high likelihood of an ASD diagnosis among patients bearing CHD8 mutations, characteristics enriched in this group included macrocephaly, distinct faces, and gastrointestinal complaints. chd8 disruption in zebrafish recapitulates features of the human phenotype, including increased head size as a result of expansion of the forebrain/midbrain and impairment of gastrointestinal motility due to a reduction in postmitotic enteric neurons. Our findings indicate that CHD8 disruptions define a distinct ASD subtype and reveal unexpected comorbidities between brain development and enteric innervation.

Convergent ablation for persistent atrial fibrillation: A UK multicentre perspective.

Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide and remains a major cause of morbidity and mortality. Unfortunately, a significant proportion of patients have persistent AF, for which conventional catheter ablation is less effective. However, convergent ablation has emerged in recent years as a hybrid treatment targeting both the epicardium and endocardium in a multidisciplinary joint cardiothoracic and electrophysiology procedure, with promising efficacy outcomes in recent studies. This treatment is increasingly being performed in the United Kingdom. This review article discusses the rationale and evidence behind convergent ablation, along with factors that need to be considered when setting up a successful ablation service.

Cost-effectiveness analysis of leadless cardiac resynchronization therapy.

BACKGROUND: The Wireless Stimulation Endocardially for CRT (WiSE-CRT) system is a novel technology used to treat patients with dyssynchronous heart failure (HF) by providing leadless cardiac resynchronization therapy (CRT). Observational studies have demonstrated its safety and efficacy profile, however, the treatment cost-effectiveness has not previously been examined. METHODS: A cost-effectiveness evaluation of the WiSE-CRT System was performed using a cohort-based economic model adopting a "proportion in state" structure. In addition to the primary analysis, scenario analyses and sensitivity analyses were performed to test for uncertainty in input parameters. Outcomes were quantified in terms of quality-adjusted life year (QALY) differences. RESULTS: The primary analysis demonstrated that treatment with the WiSE-CRT system is likely to be cost-effective over a lifetime horizon at a QALY reimbursement threshold of £20 000, with a net monetary benefit (NMB) of £3781 per QALY. Cost-effectiveness declines at time horizons shorter than 10 years. Sensitivity analyses demonstrated that average system battery life had the largest impact on potential cost-effectiveness. CONCLUSION: Within the model limitations, these findings support the use of WiSE-CRT in indicated patients from an economic standpoint. However, improving battery technology should be prioritized to maximize cost-effectiveness in times when health services are under significant financial pressures.

Predictors of Outcome in Patients with Pulmonary Hypertension Undergoing Mitral and Tricuspid Valve Surgery.

Background and Objectives: Pulmonary hypertension (PH) secondary to left-sided valvular heart disease is associated with poor cardiac surgical outcome compared with patients without PH. Our objective was to investigate the prognostic factors of surgical outcome in patients with PH undergoing mitral valve (MV) and tricuspid valve (TV) surgery, in order to risk stratify their management. Materials and Methods: This is a retrospective observational study on patients with PH who underwent MV and TV surgery from 2011 to 2019. The primary outcome was all-cause mortality. The secondary outcomes were post-op respiratory and renal complications, length of intensive care unit stay and length of hospital stay. Results: Seventy-six patients were included in this study. The all-cause mortality was 13% (n = 10), with mean survival of 92.6 months. Among the patients, 9.2% (n = 7) had post-op renal failure requiring renal replacement therapy and 6.6% (n = 5) had post-op respiratory failure requiring intubation. Univariate analysis demonstrated that pre-operative left ventricular ejection fraction (LVEF), peak systolic tissue velocity at the tricuspid annulus (S') and etiology of MV disease were associated with respiratory and renal failure. Tricuspid annular plane systolic excursion (TAPSE) was associated with respiratory failure only. S', type of operation, LVEF, urgency of surgery, and etiology of MV disease were found to be predictive of mortality. After excluding redo mitral surgery, all statistically significant findings remain unchanged, with the addition of right ventricular (RV) size being associated with respiratory failure. In the subgroup analysis of routine cases (n = 56), patients with primary mitral regurgitation who underwent mitral valve repair had better survival outcome. Conclusions: Urgency of surgery, etiology of MV disease, type of operation (replacement or repair), S' and pre-op LVEF are prognostic indicators in this small cohort of patients with PH undergoing MV and TV surgery. A larger prospective study is warranted to validate our findings.

Brainstem enlargement in preschool children with autism: Results from an intermethod agreement study of segmentation algorithms.

The intermethod agreement between automated algorithms for brainstem segmentation is investigated, focusing on the potential involvement of this structure in Autism Spectrum Disorders (ASD). Inconsistencies highlighted in previous studies on brainstem in the population with ASD may in part be a result of poor agreement in the extraction of structural features between different methods. A sample of 76 children with ASD and 76 age-, gender-, and intelligence-matched controls was considered. Volumetric analyses were performed using common tools for brain structures segmentation, namely FSL-FIRST, FreeSurfer (FS), and Advanced Normalization Tools (ANTs). For shape analysis SPHARM-MAT was employed. Intermethod agreement was quantified in terms of Pearson correlations between pairs of volumes obtained by the different methods. The degree of overlap between segmented masks was quantified in terms of the Dice index. Both Pearson correlations and Dice indices, showed poor agreement between FSL-FIRST and the other methods (ANTs and FS), which by contrast, yielded Pearson correlations greater than 0.93 and average Dice indices greater than 0.76 when compared with each other. As with volume, shape analyses exhibited discrepancies between segmentation methods, with particular differences noted between FSL-FIRST and the others (ANT and FS), with under- and over-segmentation in specific brainstem regions. These data suggest that research on brain structure alterations should cross-validate findings across multiple methods. We consistently detected an enlargement of brainstem volume in the whole sample and in the male cohort across multiple segmentation methods, a feature particularly driven by the subgroup of children with idiopathic intellectual disability associated with ASD.

Prolonged lead dwell time and lead burden predict bailout transfemoral lead extraction.

BACKGROUND: Transvenous lead extraction (TLE) may be performed by superior approach using the original implant vein or via a femoral approach; however, limited comparative data exists. We compare outcomes between femoral versus nonfemoral TLE approaches and determine predictors of bailout transfemoral lead extraction in patients undergoing initial TLE via the original implant vein by a superior approach. METHODS: All consecutive TLEs between October 2000 and March 2018 were prospectively collected (n = 1052). Patients were dichotomized into femoral (n = 118) and nonfemoral (n = 934) groups. RESULTS: Demographics were balanced between femoral vs nonfemoral groups. Patients in the femoral group had significantly higher mean lead dwell times (11.6 ± 9.7 vs 6.6 ± 6.6 years, P < .001), mean number of leads extracted (2.7 ± 1.3 vs 2.0 ± 1.0, P < .001), 30-day procedure related major complications (including deaths) (8.5% vs 1.1%, P < .001) and emergency thoracotomy rates (4.2% vs 0.7%, P = .007). All-cause 30-day mortality rates were similar between groups (3.4% vs 2.0%, P = .315). Prolonged lead dwell time and increased number of leads extracted were predictive of a bailout transfemoral approach at multivariable analysis. CONCLUSION: Femoral approach TLE is associated with increased risk of 30-day procedure related major complications but not 30-day all-cause mortality. Prolonged lead dwell time and increased number of leads extracted are independent predictors for bailout transfemoral lead extraction. Such patients should be considered high risk of major complications and performed by high-volume lead extraction centers with experience in multiple approaches and techniques including experience with transfemoral lead extraction.

The impact of automated hippocampal volumetry on diagnostic confidence in patients with suspected Alzheimer's disease: A European Alzheimer's Disease Consortium study.

INTRODUCTION: Hippocampal volume is a core biomarker of Alzheimer's disease (AD). However, its contribution over the standard diagnostic workup is unclear. METHODS: Three hundred fifty-six patients, under clinical evaluation for cognitive impairment, with suspected AD and Mini-Mental State Examination ≥20, were recruited across 17 European memory clinics. After the traditional diagnostic workup, diagnostic confidence of AD pathology (DCAD) was estimated by the physicians in charge. The latter were provided with the results of automated hippocampal volumetry in standardized format and DCAD was reassessed. RESULTS: An increment of one interquartile range in hippocampal volume was associated with a mean change of DCAD of -8.0% (95% credible interval: [-11.5, -5.0]). Automated hippocampal volumetry showed a statistically significant impact on DCAD beyond the contributions of neuropsychology, 18F-fluorodeoxyglucose positron emission tomography/single-photon emission computed tomography, and cerebrospinal fluid markers (-8.5, CrI: [-11.5, -5.6]; -14.1, CrI: [-19.3, -8.8]; -10.6, CrI: [-14.6, -6.1], respectively). DISCUSSION: There is a measurable effect of hippocampal volume on DCAD even when used on top of the traditional diagnostic workup.

Integrating longitudinal information in hippocampal volume measurements for the early detection of Alzheimer's disease.

BACKGROUND: Structural MRI measures for monitoring Alzheimer's Disease (AD) progression are becoming instrumental in the clinical practice, and more so in the context of longitudinal studies. This investigation addresses the impact of four image analysis approaches on the longitudinal performance of the hippocampal volume. METHODS: We present a hippocampal segmentation algorithm and validate it on a gold-standard manual tracing database. We segmented 460 subjects from ADNI, each subject having been scanned twice at baseline, 12-month and 24month follow-up scan (1.5T, T1 MRI). We used the bilateral hippocampal volume v and its variation, measured as the annualized volume change Λ=δv/year(mm(3)/y). Four processing approaches with different complexity are compared to maximize the longitudinal information, and they are tested for cohort discrimination ability. Reference cohorts are Controls vs. Alzheimer's Disease (CTRL/AD) and CTRL vs. Mild Cognitive Impairment who subsequently progressed to AD dementia (CTRL/MCI-co). We discuss the conditions on v and the added value of Λ in discriminating subjects. RESULTS: The age-corrected bilateral annualized atrophy rate (%/year) were: -1.6 (0.6) for CTRL, -2.2 (1.0) for MCI-nc, -3.2 (1.2) for MCI-co and -4.0 (1.5) for AD. Combined (v, Λ) discrimination ability gave an Area under the ROC curve (auc)=0.93 for CTRL vs AD and auc=0.88 for CTRL vs MCI-co. CONCLUSIONS: Longitudinal volume measurements can provide meaningful clinical insight and added value with respect to the baseline provided the analysis procedure embeds the longitudinal information.

Killer-specific secretory (Ksp37) gene expression in subjects with Down's syndrome.

Down syndrome is characterized by dysmorphic features, mental retardation and problems of immune deficiency. Chronic infection by Epstein-Barr virus is frequently present in subjects with Down syndrome. Ksp37 gene is commonly expressed by NK, CD8(+) T, γδ T and CD4(+) T cells; these data suggest that Ksp37 have cytotoxic properties. An increase of Ksp37 protein serum levels it has been showed during the acute phase of Epstein-Barr virus. In this study, we evaluated the expression of Ksp37 mRNA, in fibroblasts and leukocytes of DS subjects and in normal subjects with realtime reverse transcription-PCR. This analysis shows that in fibroblasts and leukocytes of Down syndrome subjects the KSP37 gene expression was increased compared with control subjects. The results of this study suggest that the expression of Ksp37 gene might be associated with increased susceptibility of individuals with Down syndrome to EBV infections and autoimmune problems.

LDOC1 Gene Expression in Men With Klinefelter Syndrome.

Klinefelter syndrome (KS) results from an extra chromosome X, which is due to the failure of normal chromosomal segregation during meiosis. Patients with KS have gynecomastia, small testes, and azoospermia. Apoptosis is a mechanism responsible for the normal regulation of spermatogenesis. LDOC1 gene is a known regulator of nuclear factor mediated pathway to apoptosis through inhibition of nuclear factor kappa B (NF-kappaB). Furthermore, the transcription factor myeloid zinc finger gene 1 (MZF-1) has been shown to interact with LDOC1 and to enhance LDOC1 activity favoring apoptosis. We investigated the expression of LDOC1 gene mRNA, by quantitative reverse transcription polymerase chain reaction (qRT-PCR), in peripheral blood leukocytes of 13 patients with KS compared to 13 healthy men chosen as controls. LDOC1 expression was higher in 9 of the 13 KS patient compared to normal controls. These finding led us to hypothesize that LDOC1 gene upregulation may play a role in the spermatogenesis derangement observed in patients with KS.

Expression of Phosphodiesterase 4B cAMP-Specific Gene in Subjects With Cryptorchidism and Down's Syndrome.

Cryptorchidism represents a risk factor for infertility and germ cell testicular neoplasia. An increased rate of cryptorchidism has been reported in subjects with Down's syndrome. Cyclic nucleotide phosphodiesterases (PDEs) are important messengers that regulate and mediate a number of cellular responses to extracellular signals, such as neurotransmitters and hormones. PDE4B, cAMP-specific (PDE4B) gene which maps to chromosome 1p31.3 appears to be involved in schizophrenia, chronic psychiatric illness, learning, memory, and mood disturbances. Expression of PDE4 enzymes have been studied in testes of cryptorchid rats. Expression of PDE4B protein examination showed marked degenerative changes in the epithelial lining of the seminiferous tubules. These findings led us to evaluate PDE4 mRNA expression in leukocytes of peripheral blood of five men with DS and cryptorchidism and eleven subjects with DS without cryptorchidism compared with healthy men (controls) by quantitative Real Time PCR (qRT-PCR). This study showed that the PDE4B gene was downexpressed in men with DS and cryptorchidism compared to normal controls and DS without cryptorchidism. A lower expression of the PDE4B gene may be involved in the neurological abnormalities in subjects with Down's syndrome. Moreover, PDE4B gene may be involved in the testicular abnormalities of men with DS and cryptorchidism.

An inflammatory and trophic disconnect biomarker profile revealed in Down syndrome plasma: Relation to cognitive decline and longitudinal evaluation.

INTRODUCTION: Given that Alzheimer's pathology develops silently over decades in Down syndrome (DS), prognostic biomarkers of dementia are a major need. METHODS: We investigated the plasma levels of Aß, proNGF, tPA, neuroserpin, metallo-proteases and inflammatory molecules in 31 individuals with DS (with and without dementia) and in 31 healthy controls. We examined associations between biomarkers and cognitive decline. RESULTS: Aß40 and Aß42 were elevated in DS plasma compared to controls, even in DS individuals without dementia. Plasma Aß correlated with the rate of cognitive decline across 2 years. ProNGF, MMP-1, MMP-3, MMP-9 activity, TNF-α, IL-6, and IL-10 were higher in DS plasma, even at AD-asymptomatic stages. Declining plasma Aß42 and increasing proNGF levels correlated with cognitive decline. A combined measure of Aß and inflammatory molecules was a strong predictor of prospective cognitive deterioration. CONCLUSIONS: Our findings support the combination of plasma and cognitive assessments for the identification of DS individuals at risk of dementia.

Excess of runs of homozygosity is associated with severe cognitive impairment in intellectual disability.

PURPOSE: The harmful effects of inbreeding are well known by geneticists, and several studies have already reported cases of intellectual disability caused by recessive variants in consanguineous families. Nevertheless, the effects of inbreeding on the degree of intellectual disability are still poorly investigated. Here, we present a detailed analysis of the homozygosity regions in a cohort of 612 patients with intellectual disabilities of different degrees. METHODS: We investigated (i) the runs of homozygosity distribution between syndromic and nonsyndromic ID (ii) the effect of runs of homozygosity on the ID degree, using the intelligence quotient score. RESULTS: Our data revealed no significant differences in the first analysis; instead we detected significantly larger runs of homozygosity stretches in severe ID compared to nonsevere ID cases (P = 0.007), together with an increase of the percentage of genome covered by runs of homozygosity (P = 0.03). CONCLUSION: In accord with the recent findings regarding autism and other neurological disorders, this study reveals the important role of autosomal recessive variants in intellectual disability. The amount of homozygosity seems to modulate the degree of cognitive impairment despite the intellectual disability cause.

The EADC-ADNI Harmonized Protocol for manual hippocampal segmentation on magnetic resonance: evidence of validity.

BACKGROUND: An international Delphi panel has defined a harmonized protocol (HarP) for the manual segmentation of the hippocampus on MR. The aim of this study is to study the concurrent validity of the HarP toward local protocols, and its major sources of variance. METHODS: Fourteen tracers segmented 10 Alzheimer's Disease Neuroimaging Initiative (ADNI) cases scanned at 1.5 T and 3T following local protocols, qualified for segmentation based on the HarP through a standard web-platform and resegmented following the HarP. The five most accurate tracers followed the HarP to segment 15 ADNI cases acquired at three time points on both 1.5 T and 3T. RESULTS: The agreement among tracers was relatively low with the local protocols (absolute left/right ICC 0.44/0.43) and much higher with the HarP (absolute left/right ICC 0.88/0.89). On the larger set of 15 cases, the HarP agreement within (left/right ICC range: 0.94/0.95 to 0.99/0.99) and among tracers (left/right ICC range: 0.89/0.90) was very high. The volume variance due to different tracers was 0.9% of the total, comparing favorably to variance due to scanner manufacturer (1.2), atrophy rates (3.5), hemispheric asymmetry (3.7), field strength (4.4), and significantly smaller than the variance due to atrophy (33.5%, P < .001), and physiological variability (49.2%, P < .001). CONCLUSIONS: The HarP has high measurement stability compared with local segmentation protocols, and good reproducibility within and among human tracers. Hippocampi segmented with the HarP can be used as a reference for the qualification of human tracers and automated segmentation algorithms.

The MTRR 66A>G polymorphism and maternal risk of birth of a child with Down syndrome in Caucasian women: a case-control study and a meta-analysis.

We performed a large case-control study and a meta-analysis of the literature to address the role of the methionine synthase reductase (MTRR) c.66A>G polymorphism as a maternal risk factor for the birth of a child with Down Syndrome (DS) among Caucasian women. A total of 253 mothers of a DS child (MDS) and 298 control mothers of Italian origin were included in the case-control study. The meta-analysis of previous and present data involved a total of seven studies performed in Caucasian populations (971 MDS and 1,387 control mothers). Results from the meta-analysis indicated overall a positive significant association between MTRR c.66A>G genotype [OR 1.36 (95 % CI 1.10-1.68), dominant model] and allele frequencies [OR 1.26 (95 % CI 1.04-1.51), allele contrast model] and maternal risk of birth of a child with DS. A sensitivity analysis revealed some interesting differences between Europeans, Caucasians of European descent, and inhabitants of Mediterranean regions, suggesting the possibility of population-specific modifying factors. The case-control study revealed association of the polymorphism with increased folate levels, and a possible interaction with the methionine synthase (MTR) c.2756A>G one, that resulted in a borderline significant maternal risk of birth of a child with DS for the double heterozygous MTR 2756AG/MTRR 66AG genotype [OR 1.79 (95 % CI 1.00-3.18)]. Overall, present data suggest that the MTRR c.66A>G polymorphism represents a risk factor for the birth of a child with DS among white Caucasian women. However, the combined presence of other genetic factors and interactions with geographic and environmental ones, can modify the effect of the single polymorphism alone, leading to population specific effect sizes.

"Postural first" principle when balance is challenged in elderly people.

Human cognitive processing limits can lead to difficulties in performing two tasks simultaneously. This study aimed to evaluate the effect of cognitive load on both simple and complex postural tasks. Postural control was evaluated in 128 noninstitutionalized elderly people (mean age = 73.6 ± 5.6 years) using a force platform on a firm support in control condition (CC) and mental counting condition (MCC) with eyes open (EO) and eyes closed (EC). Then, the same tests were performed on a foam support. Sway path traveled and area covered by the center of foot pressure were recorded, low values indicating efficient balance. On firm support, sway path was higher in MCC than in CC both in EO and EC conditions (p < 0.001). On foam support, sway path was higher in CC than in MCC in EC condition (p < 0.001), area being higher in CC than in MCC both in EO (p < 0.05) and EC (p < 0.001) conditions. The results indicate that cognitive load alters balance control in a simple postural task (i.e. on firm support), which is highlighted by an increase of energetic expenditure (i.e. increase of the sway path covered) to balance. Awareness may not be increased and the attentional demand may be shared between balance and mental task. Conversely, cognitive load does not perturb the realization of a new complex postural task. This result showed that postural control is prioritized ("postural first" principle) when seriously challenged.

Automatic temporal lobe atrophy assessment in prodromal AD: Data from the DESCRIPA study.

BACKGROUND: In the framework of the clinical validation of research tools, this investigation presents a validation study of an automatic medial temporal lobe atrophy measure that is applied to a naturalistic population sampled from memory clinic patients across Europe. METHODS: The procedure was developed on 1.5-T magnetic resonance images from the Alzheimer's Disease Neuroimaging Initiative database, and it was validated on an independent data set coming from the DESCRIPA study. All images underwent an automatic processing procedure to assess tissue atrophy that was targeted at the hippocampal region. For each subject, the procedure returns a classification index. Once provided with the clinical assessment at baseline and follow-up, subjects were grouped into cohorts to assess classification performance. Each cohort was divided into converters (co) and nonconverters (nc) depending on the clinical outcome at follow-up visit. RESULTS: We found the area under the receiver operating characteristic curve (AUC) was 0.81 for all co versus nc subjects, and AUC was 0.90 for subjective memory complaint (SMCnc) versus all co subjects. Furthermore, when training on mild cognitive impairment (MCI-nc/MCI-co), the classification performance generally exceeds that found when training on controls versus Alzheimer's disease (CTRL/AD). CONCLUSIONS: Automatic magnetic resonance imaging analysis may assist clinical classification of subjects in a memory clinic setting even when images are not specifically acquired for automatic analysis.

Novel Techniques and Technologies for Surgical Aortic Valve Replacement: A Large Retrospective Cohort Analysis.

Background/Objectives: In an era of growing evidence for transaortic valve implantation (TAVI), our research topic was the evaluation of how surgical aortic valve replacements (SAVRs) are performing in terms of short- and long-term outcomes in different risk categories. Methods: This was a single centre, prospective, and observational cohort study of consecutive patients with aortic valve stenosis, undergoing isolated aortic valve replacement using a biological or mechanical prosthesis, Freestyle™ (Medtronic, Minneapolis, MN, USA) graft, homograft, or Ross procedure. The participant data were collected by review of an internal database. The primary endpoints were all-cause operative mortality (in hospital and at 30 days) and late mortality at the follow-up date. The secondary composite endpoint was the incidence of postoperative complications. Results: 1501 patients underwent SAVR; the mean age was 67 years (SD: 12.6). The in-hospital mortality was 1% (n = 16). At a median follow-up of 60 months, the survival rate was 98.7%. The main predictors for mortality were operative urgency and cardiogenic shock. The overall incidence of PPM was 2.3% (n = 34). Patients who underwent Ross procedure were younger (mean age: 20 years (SD: 1.7)), had a lower incidence of postoperative complications, and were all alive at follow-up. Conclusions: SAVR shows an excellent survival rate and a low rate of postoperative complications despite an increasing surgical risk. Recent advancements in technology, like sutureless/rapid deployment prostheses and minimally invasive techniques, are shown to have favourable effects on outcomes.

Time-of-flight MRA of intracranial vessels at 7 T.

BACKGROUND: Three-dimensional time-of-flight magnetic resonance angiography (TOF-MRA) is a largely adopted non-invasive technique for assessing cerebrovascular diseases. We aimed to optimize the 7-T TOF-MRA acquisition protocol, confirm that it outperforms conventional 3-T TOF-MRA, and compare 7-T TOF-MRA with digital subtraction angiography (DSA) in patients with different vascular pathologies. METHODS: Seven-tesla TOF-MRA sequences with different spatial resolutions acquired in four healthy subjects were compared with 3-T TOF-MRA for signal-to-noise and contrast-to-noise ratios as well as using a qualitative scale for vessel visibility and the quantitative Canny algorithm. Four patients with cerebrovascular disease (primary arteritis of the central nervous system, saccular aneurism, arteriovenous malformation, and dural arteriovenous fistula) underwent optimized 7-T TOF-MRA and DSA as reference. Images were compared visually and using the complex-wavelet structural similarity index. RESULTS: Contrast-to-noise ratio was higher at 7 T (4.5 ± 0.8 (mean ± standard deviation)) than at 3 T (2.7 ± 0.9). The mean quality score for all intracranial vessels was higher at 7 T (2.89) than at 3 T (2.28). Angiogram quality demonstrated a better vessel border detection at 7 T than at 3 T (44,166 versus 28,720 pixels). Of 32 parameters used for diagnosing cerebrovascular diseases on DSA, 27 (84%) were detected on 7-T TOF-MRA; the similarity index ranged from 0.52 (dural arteriovenous fistula) to 0.90 (saccular aneurysm). CONCLUSIONS: Seven-tesla TOF-MRA outperformed conventional 3-T TOF-MRA in evaluating intracranial vessels and exhibited an excellent image quality when compared to DSA. Seven-tesla TOF-MRA might improve the non-invasive diagnostic approach to several cerebrovascular diseases. RELEVANCE STATEMENT: An optimized TOF-MRA sequence at 7 T outperforms 3-T TOF-MRA, opening perspectives to its clinical use for noninvasive diagnosis of paradigmatic pathologies of intracranial vessels. KEY POINTS: • An optimized 7-T TOF-MRA protocol was selected for comparison with clinical 3-T TOF-MRA for assessing intracranial vessels. • Seven-tesla TOF-MRA outperformed 3-T TOF-MRA in both quantitative and qualitative evaluation. • Seven-tesla TOF-MRA is comparable to DSA for the diagnosis and characterization of intracranial vascular pathologies.

Optimizing electrical efficacy of leadless cardiac resynchronization therapy and leadless left ventricular septal pacing: Insights on left and right ventricular activation from electrocardiographic imaging.

Background: Leadless cardiac resynchronization therapy (CRT) is an emerging heart failure treatment. An implanted electrode delivers lateral or septal endocardial left ventricular (LV) pacing (LVP) upon detection of a right ventricular (RV) pacing stimulus from a coimplanted device, thus generating biventricular pacing (BiVP). Electrical efficacy data regarding this therapy, particularly leadless LV septal pacing (LVSP) for potential conduction system capture, are limited. Objectives: The purpose of this study was to evaluate the acute performance of leadless CRT using electrocardiographic imaging (ECGi) and assess the optimal pacing modality (OPM) of LVSP on the basis of RV and LV activation. Methods: Ten WiSE-CRT recipients underwent an ECGi study testing: RV pacing, BiVP, LVP only, and LVP with an optimized atrioventricular delay (LV-OPT). BiV, LV, and RV activation times (shortest time taken to activate 90% of the ventricles [BIVAT-90], shortest time taken to activate 95% of the LV, and shortest time taken to activate 90% of the RV) plus LV and BiV dyssynchrony index (standard deviation of LV activation times and standard deviation of all activation times) were calculated from reconstructed epicardial electrograms. The individual OPM yielding the greatest improvement from baseline was determined. Results: BiVP generated a 23.7% improvement in BiVAT-90 (P = .002). An improvement of 43.3% was observed at the OPM (P = .0001), primarily through reductions in shortest time taken to activate 90% of the RV. At the OPM, BiVAT-90 improved in patients with lateral (43.3%; P = .0001; n = 5) and septal (42.4%; P = .009; n = 5) LV implants. The OPM varied by individual. LVP and LV-OPT were mostly superior in patients with LVSP, and in those with sinus rhythm and left bundle branch block (n = 4). Conclusion: Leadless CRT significantly improves acute ECGi-derived activation and dyssynchrony metrics. Using an individualized OPM improves efficacy in selected patients. Effective LVSP is feasible, with fusion pacing at LV-OPT mitigating the potential deleterious effects on RV activation.