Interventions aimed to increase average 24-h systolic blood pressure reduce blood pressure drops in patients with reflex syncope and orthostatic intolerance.

AIMS: Systolic blood pressure (SBP) drops recorded by 24-h ambulatory blood pressure (BP) monitoring (ABPM) identify patients with susceptibility to reflex syncope and orthostatic intolerance. We tested the hypothesis that treatments aimed to increase BP (reassurance, education, and lifestyle measures plus pharmacological strategies) can reduce SBP drops. METHODS AND RESULTS: This was a multicentre, observational proof-of-concept study performed in patients with reflex syncope and/or orthostatic intolerance and with SBP drops on a screening ABPM. Among 144 eligible patients, 111 underwent a second ABPM on average 2.5 months after start of treatment. Overall, mean 24-h SBP increased from 114.1 ± 12.1 to 121.4 ± 14.5 mmHg (P < 0.0001). The number of SBP drops <90 and <100 mmHg decreased by 61%, 46% during daytime, and by 48% and 37% during 24-h period, respectively (P < 0.0001 for all). The dose-response relationship between difference in 24-h average SBP increase and reduction in number of SBP drops reached a plateau around ∼15 mmHg increase of 24-h SBP. The reduction in SBP drop rate was consistent and significant in patients who underwent deprescription of hypotensive medications (n = 44) and in patients who received BP-rising drugs (n = 67). CONCLUSION: In patients with reflex syncope and/or orthostatic intolerance, an increase in average 24-h SBP, regardless of the implemented strategy, significantly reduced the number of SBP drops and symptom burden. A 13 mmHg increase in 24-h SBP appears to represent the optimal goal for aborting the maximal number of SBP drops, representing a possible target for future interventions. ClincalTrials.gov identifier: NCT05729724.

Tilt table testing, methodology and practical insights for the clinic.

Tilt table testing (TTT) has been used for decades to study short-term blood pressure (BP) and heart rate regulation during orthostatic challenges. TTT provokes vasovagal reflex in many syncope patients as a background of widespread use. Despite the availability of evidence-based practice syncope guidelines, proper application and interpretation of TTT in the day-to-day care of syncope patients remain challenging. In this review, we offer practical information on what is needed to perform TTT, how results should be interpreted including the Vasovagal Syncope International Study classification, why syncope induction on TTT is necessary in patients with unexplained syncope and on indications for TTT in syncope patient care. The minimum requirements to perform TTT are a tilt table with an appropriate tilt-down time, a continuous beat-to-beat BP monitor with at least three electrocardiogram leads and trained staff. We emphasize that TTT remains a valuable asset that adds to history building but cannot replace it, and highlight the importance of recognition when TTT is abnormal even without syncope. Acknowledgement by the patient/eyewitness of the reproducibility of the induced attack is mandatory in concluding a diagnosis. TTT may be indicated when the initial syncope evaluation does not yield a certain, highly likely, or possible diagnosis, but raises clinical suspicion of (1) reflex syncope, (2) orthostatic hypotension (OH), (3) postural orthostatic tachycardia syndrome or (4) psychogenic pseudosyncope. A therapeutic indication for TTT in the patient with a certain, highly likely or possible diagnosis of reflex syncope, may be to educate patients on prodromes. In patients with reflex syncope with OH TTT can be therapeutic to recognize hypotensive symptoms causing near-syncope to perform physical countermanoeuvres for syncope prevention (biofeedback). Detection of hypotensive susceptibility requiring therapy is of special value.

Digital consults to optimize guideline-directed therapy: design of a pragmatic multicenter randomized controlled trial.

AIMS: Many heart failure (HF) patients do not receive optimal guideline-directed medical therapy (GDMT) despite clear benefit on morbidity and mortality outcomes. Digital consults (DCs) have the potential to improve efficiency on GDMT optimization to serve the growing HF population. The investigator-initiated ADMINISTER trial was designed as a pragmatic multicenter randomized controlled open-label trial to evaluate efficacy and safety of DC in patients on HF treatment. METHODS AND RESULTS: Patients (n = 150) diagnosed with HF with a reduced ejection fraction will be randomized to DC or standard care (1:1). The intervention group receives multifaceted DCs including (i) digital data sharing (e.g. exchange of pharmacotherapy use and home-measured vital signs), (ii) patient education via an e-learning, and (iii) digital guideline recommendations to treating clinicians. The consults are performed remotely unless there is an indication to perform the consult physically. The primary outcome is the GDMT prescription rate score, and secondary outcomes include time till full GDMT optimization, patient and clinician satisfaction, time spent on healthcare, and Kansas City Cardiomyopathy Questionnaire. Results will be reported in accordance to the CONSORT statement. CONCLUSIONS: The ADMINISTER trial will offer the first randomized controlled data on GDMT prescription rates, time till full GDMT optimization, time spent on healthcare, quality of life, and patient and clinician satisfaction of the multifaceted patient- and clinician-targeted DC for GDMT optimization.

Variability of cardioinhibition in vasovagal syncope: differences between subgroups during cardioinhibition and beyond.

PURPOSE: We compared hemodynamic parameters between subjects with marked, intermediate and minimal cardioinhibition during vasovagal syncope. METHODS: The study included subjects with a decrease in heart rate while experiencing a complete vasovagal syncope during tilt-table testing. The subjects were classified as having marked, intermediate or minimal cardioinhibition, based on tertile values of the decrease in heart rate. Hemodynamic parameters between these groups were compared before tilt in the supine position, shortly after tilt and during cardioinhibition. RESULTS: A total of 149 subjects with a median age of 43 (interquartile range 24-60) years were included in the study. Among the three groups with different levels of cardioinhibition, the highest heart rate was observed in subjects with marked cardioinhibition both before and shortly after tilt and at the start of cardioinhibition. The heart rate decrease in these subjects was both larger and faster compared to subjects with minimal and intermediate cardioinhibition. CONCLUSION: Subjects with marked cardioinhibition have both a larger and faster decrease in heart rate compared to subjects with intermediate and minimal cardioinhibition, as early as from the start of cardioinhibition. Marked cardioinhibition is related to differences in hemodynamic profiles already present well before the start of cardioinhibition.

Twenty-five years of research on syncope.

Over the last 25 years, the Europace journal has greatly contributed to dissemination of research and knowledge in the field of syncope. More than 400 manuscripts have been published in the journal. They undoubtedly improved our understanding of syncope. This symptom is now clearly differentiated from other forms of transient loss of consciousness. The critical role of vasodepression and/or cardioinhibition as final mechanisms of reflex syncope is emphasized. Current diagnostic approach sharply separates between cardiac and autonomic pathways. Physiologic insights have been translated, through rigorously designed clinical trials, into non-pharmacological or pharmacological interventions and interventional therapies. The following manuscript is intended to give the reader the current state of the art of knowledge of syncope by highlighting landmark contributions of the Europace journal.

Syncope Diagnosis at Referral to a Tertiary Syncope Unit: An in-Depth Analysis of the FAST II.

OBJECTIVE: A substantial number of patients with a transient loss of consciousness (T-LOC) are referred to a tertiary syncope unit without a diagnosis. This study investigates the final diagnoses reached in patients who, on referral, were undiagnosed or inaccurately diagnosed in secondary care. METHODS: This study is an in-depth analysis of the recently published Fainting Assessment Study II, a prospective cohort study in a tertiary syncope unit. The diagnosis at the tertiary syncope unit was established after history taking (phase 1), following autonomic function tests (phase 2), and confirming after critical follow-up of 1.5-2 years, with the adjudicated diagnosis (phase 3) by a multidisciplinary committee. Diagnoses suggested by the referring physician were considered the phase 0 diagnosis. We determined the accuracy of the phase 0 diagnosis by comparing this with the phase 3 diagnosis. RESULTS: 51% (134/264) of patients had no diagnosis upon referral (phase 0), the remaining 49% (130/264) carried a diagnosis, but 80% (104/130) considered their condition unexplained. Of the patients undiagnosed at referral, three major causes of T-LOC were revealed: reflex syncope (69%), initial orthostatic hypotension (20%) and psychogenic pseudosyncope (13%) (sum > 100% due to cases with multiple causes). Referral diagnoses were either inaccurate or incomplete in 65% of the patients and were mainly altered at tertiary care assessment to reflex syncope, initial orthostatic hypotension or psychogenic pseudosyncope. A diagnosis of cardiac syncope at referral proved wrong in 17/18 patients. CONCLUSIONS: Syncope patients diagnosed or undiagnosed in primary and secondary care and referred to a syncope unit mostly suffer from reflex syncope, initial orthostatic hypotension or psychogenic pseudosyncope. These causes of T-LOC do not necessarily require ancillary tests, but can be diagnosed by careful history-taking. Besides access to a network of specialized syncope units, simple interventions, such as guideline-based structured evaluation, proper risk-stratification and critical follow-up may reduce diagnostic delay and improve diagnostic accuracy for syncope.

Applying systems thinking to unravel the mechanisms underlying orthostatic hypotension related fall risk.

Orthostatic hypotension (OH) is an established and common cardiovascular risk factor for falls. An in-depth understanding of the various interacting pathophysiological pathways contributing to OH-related falls is essential to guide improvements in diagnostic and treatment opportunities. We applied systems thinking to multidisciplinary map out causal mechanisms and risk factors. For this, we used group model building (GMB) to develop a causal loop diagram (CLD). The GMB was based on the input of experts from multiple domains related to OH and falls and all proposed mechanisms were supported by scientific literature. Our CLD is a conceptual representation of factors involved in OH-related falls, and their interrelatedness. Network analysis and feedback loops were applied to analyze and interpret the CLD, and quantitatively summarize the function and relative importance of the variables. Our CLD contains 50 variables distributed over three intrinsic domains (cerebral, cardiovascular, and musculoskeletal), and an extrinsic domain (e.g., medications). Between the variables, 181 connections and 65 feedback loops were identified. Decreased cerebral blood flow, low blood pressure, impaired baroreflex activity, and physical inactivity were identified as key factors involved in OH-related falls, based on their high centralities. Our CLD reflects the multifactorial pathophysiology of OH-related falls. It enables us to identify key elements, suggesting their potential for new diagnostic and treatment approaches in fall prevention. The interactive online CLD renders it suitable for both research and educational purposes and this CLD is the first step in the development of a computational model for simulating the effects of risk factors on falls.

A cross-sectional nationwide survey of guideline based syncope units in the Netherlands: the SU-19 score-a novel validation for best practices.

AIMS: We aimed to identify all syncope units (SUs) in the Netherlands and assess the extent to which these SUs fulfil the essential requirements outlined by the consensus statements of the European Heart Rhythm Association and the European Society of Cardiology syncope guidelines. For this, we developed the SU-19 score, a novel guideline based validation tool for best practice. METHODS AND RESULTS: All outpatient clinics of cardiology, neurology, and internal medicine in the Netherlands were screened for presence of any form of structured specialized syncope care. If present, these were included as SUs and requested to complete a questionnaire regarding syncope care. We assessed all SUs using the SU-19 score regarding structure (3 points), available tests (12 points), and initial evaluation (4 points). Twenty SUs were identified in the Netherlands, both academic (5/20) and non-academic hospitals (15/20), 17/20 reported multidisciplinary involvement during initial evaluation. In 19/20, neurology, cardiology, or both were responsible for the syncope management. Non-physicians were involved performing the head-up tilt test (44%) and initial evaluation (40%). The mean SU-19 score was 18.0 ± 1.1, 45% achieved the maximum score of 19 points. Variations were observed in protocols for active standing test, carotid sinus massage, and head-up tilt test. CONCLUSION: There is a network of 20 SUs in the Netherlands. Forty-five per cent fully met the SU-19 score (mean 18.0 ± 1.1). Slight variety existed in protocols for autonomic function tests. Neurology and cardiology were mostly involved in syncope management. Non-physicians play an important role in syncope care.

Estimating axial diffusivity in the NODDI model.

To estimate microstructure-related parameters from diffusion MRI data, biophysical models make strong, simplifying assumptions about the underlying tissue. The extent to which many of these assumptions are valid remains an open research question. This study was inspired by the disparity between the estimated intra-axonal axial diffusivity from literature and that typically assumed by the Neurite Orientation Dispersion and Density Imaging (NODDI) model (d∥=1.7µm2/ms). We first demonstrate how changing the assumed axial diffusivity results in considerably different NODDI parameter estimates. Second, we illustrate the ability to estimate axial diffusivity as a free parameter of the model using high b-value data and an adapted NODDI framework. Using both simulated and in vivo data we investigate the impact of fitting to either real-valued or magnitude data, with Gaussian and Rician noise characteristics respectively, and what happens if we get the noise assumptions wrong in this high b-value and thus low SNR regime. Our results from real-valued human data estimate intra-axonal axial diffusivities of ∼2-2.5µm2/ms, in line with current literature. Crucially, our results demonstrate the importance of accounting for both a rectified noise floor and/or a signal offset to avoid biased parameter estimates when dealing with low SNR data.

Influence of Age on Magnitude and Timing of Vasodepression and Cardioinhibition in Tilt-Induced Vasovagal Syncope.

BACKGROUND: Cardioinhibition may diminish with age, but the changing balance of cardioinhibition and vasodepression with age has not been quantified, leaving the mechanism of vasovagal syncope (VVS) in old age unclear. OBJECTIVES: This study sought to quantify age-related changes of vasodepression and cardioinhibition in tilt-induced VVS. METHODS: We studied 163 cases of tilt-induced VVS, evoked using the Italian protocol with blood pressure, heart rate, and video-electroencephalographic monitoring. Presyncope was excluded. Cardioinhibition was defined as the heart rate decrease before syncope; asystolic pauses (≥3 seconds) were divided into early and late asystole, ie, beginning early enough to or too late to be the major cause of loss of consciousness. The log-ratio method was used to quantify contributions of cardioinhibition and vasodepression, assessed in 2 10-second periods before the onset of cardioinhibition and before syncope. RESULTS: With increasing age, cardioinhibition decreased, ie, heart rate decreased less and more slowly near syncope (P < 0.0001), while vasodepression increased. Asystolic pauses were less frequent in the older one-half of the group than the younger one-half (26% vs 57%; P < 0.00001), but when it did, late asystole occurred more often (58% vs 15%; P < 0.001). CONCLUSIONS: The shift toward less cardioinhibition and more vasodepression with increased age probably reflects a physiological shift in circulatory control. The weakening of cardioinhibition with age may detract from the efficacy of pacing in older patients with VVS. Cardioinhibition-vasodepression balance should be considered in pacing decisions in older subjects with VVS.

[Transient loss of consciousness]. / Wegrakingen.

Although transient loss of consciousness (TLOC) is a common problem, hospital care for patients with TLOC is characterised by high rates of no diagnosis and misdiagnosis, accompanied by unnecessary hospital admissions and tests. We attribute these problems to increasing specialisation as well as to a blind spot for vasovagal syncope, a condition not claimed by any specialty. We suggest that all doctors seeing patients with TLOC, both in primary and secondary care, should be familiar with the presentations of the relatively harmless vasovagal syncope and the alarm symptoms of potentially life-threatening cardiac syncope. In this article we present some practical pointers to recognise these conditions and answer some frequently-asked questions regarding the diagnosis and treatment of TLOC.

Cortical Morphology and White Matter Tractography of Three Phylogenetically Distant Primates: Evidence for a Simian Elaboration.

Comparative neuroimaging has been used to identify changes in white matter architecture across primate species phylogenetically close to humans, but few have compared the phylogenetically distant species. Here, we acquired postmortem diffusion imaging data from ring-tailed lemurs (Lemur catta), black-capped squirrel monkeys (Saimiri boliviensis), and rhesus macaques (Macaca mulatta). We were able to establish templates and surfaces allowing us to investigate sulcal, cortical, and white matter anatomy. The results demonstrate an expansion of the frontal projections of the superior longitudinal fasciculus complex in squirrel monkeys and rhesus macaques compared to ring-tailed lemurs, which correlates with sulcal anatomy and the lemur's smaller prefrontal granular cortex. The connectivity of the ventral pathway in the parietal region is also comparatively reduced in ring-tailed lemurs, with the posterior projections of the inferior longitudinal fasciculus not extending toward parietal cortical areas as in the other species. In the squirrel monkeys we note a very specific occipito-parietal anatomy that is apparent in their surface anatomy and the expansion of the posterior projections of the optical radiation. Our study supports the hypothesis that the connectivity of the prefrontal-parietal regions became relatively elaborated in the simian lineage after divergence from the prosimian lineage.

Adapting the UK Biobank Brain Imaging Protocol and Analysis Pipeline for the C-MORE Multi-Organ Study of COVID-19 Survivors.

SARS-CoV-2 infection has been shown to damage multiple organs, including the brain. Multiorgan MRI can provide further insight on the repercussions of COVID-19 on organ health but requires a balance between richness and quality of data acquisition and total scan duration. We adapted the UK Biobank brain MRI protocol to produce high-quality images while being suitable as part of a post-COVID-19 multiorgan MRI exam. The analysis pipeline, also adapted from UK Biobank, includes new imaging-derived phenotypes (IDPs) designed to assess the possible effects of COVID-19. A first application of the protocol and pipeline was performed in 51 COVID-19 patients post-hospital discharge and 25 controls participating in the Oxford C-MORE study. The protocol acquires high resolution T1, T2-FLAIR, diffusion weighted images, susceptibility weighted images, and arterial spin labelling data in 17 min. The automated imaging pipeline derives 1,575 IDPs, assessing brain anatomy (including olfactory bulb volume and intensity) and tissue perfusion, hyperintensities, diffusivity, and susceptibility. In the C-MORE data, IDPs related to atrophy, small vessel disease and olfactory bulbs were consistent with clinical radiology reports. Our exploratory analysis tentatively revealed some group differences between recovered COVID-19 patients and controls, across severity groups, but not across anosmia groups. Follow-up imaging in the C-MORE study is currently ongoing, and this protocol is now being used in other large-scale studies. The protocol, pipeline code and data are openly available and will further contribute to the understanding of the medium to long-term effects of COVID-19.

Heart rate distribution in paced and non-paced patients with severe recurrent reflex syncope and tilt-induced asystole: Findings from the BIOSync CLS study.

BACKGROUND: Undiagnosed sinus or atrioventricular node dysfunction may bias estimation of the real efficacy of cardiac pacing in preventing vasovagal reflex syncope. We assessed this hypothesis in the BIOSync CLS trial which showed that dual-chamber pacing with closed loop stimulation (CLS) remarkably reduced recurrences of syncope. METHODS AND RESULTS: In the study patients aged 40 years or older with ≥2 episodes of loss of consciousness in the last year and an asystolic response to Tilt-Table test were randomized to pacing ON (DDD-CLS mode) or pacing OFF (ODO mode). We utilized the available pacemaker diagnostic data in a total of 103 patients (52 pacing ON, 51 pacing OFF) to generate cumulative distribution charts for heart rate (HR) and percentage of pacing. At 12 months, we did not find evidence of suspected sinus or atrioventricular node dysfunction. Beats were similarly distributed between groups (p = 0.96), with an average HR of 76 ± 8 bpm (pacing ON) versus 77 ± 7 bpm (pacing OFF). In the active group, the median percentage of atrial and ventricular pacing was 47% and 0%, respectively. Intolerance to high pacing rates was reported in only one patient (1.6%) and was easily resolved by reprogramming the maximum CLS pacing rate. CONCLUSIONS: We did not find evidence of suspected sinus or atrioventricular node dysfunction in the BIOSync CLS patients. The benefit of pacing should be ascribed to pacing prevention of pure vasovagal episodes. CLS algorithm modulated pacing rates over a wide frequency range, consistently competing with sinus node.

Segment length in cine (SLICE) strain analysis: a practical approach to estimate potential benefit from cardiac resynchronization therapy.

BACKGROUND: Segment length in cine (SLICE) strain analysis on standard cardiovascular magnetic resonance (CMR) cine images was recently validated against gold standard myocardial tagging. The present study aims to explore predictive value of SLICE for cardiac resynchronization therapy (CRT) response. METHODS AND RESULTS: Fifty-seven patients with heart failure and left bundle branch block (LBBB) were prospectively enrolled in this multi-center study and underwent CMR examination before CRT implantation. Circumferential strains of the septal and lateral wall were measured by SLICE on short-axis cine images. In addition, timing and strain pattern parameters were assessed. After twelve months, CRT response was quantified by the echocardiographic change in left ventricular (LV) end-systolic volume (LVESV). In contrast to timing parameters, strain pattern parameters being systolic rebound stretch of the septum (SRSsep), systolic stretch index (SSIsep-lat), and internal stretch factor (ISFsep-lat) all correlated significantly with LVESV change (R - 0.56; R - 0.53; and R - 0.58, respectively). Of all strain parameters, end-systolic septal strain (ESSsep) showed strongest correlation with LVESV change (R - 0.63). Multivariable analysis showed ESSsep to be independently related to LVESV change together with age and QRSAREA. CONCLUSION: The practicable SLICE strain technique may help the clinician to estimate potential benefit from CRT by analyzing standard CMR cine images without the need for commercial software. Of all strain parameters, end-systolic septal strain (ESSsep) demonstrates the strongest correlation with reverse remodeling after CRT. This parameter may be of special interest in patients with non-strict LBBB morphology for whom CRT benefit is doubted.

Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge.

BACKGROUND: The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood. METHODS: Fifty-eight COVID-19 patients post-hospital discharge and 30 age, sex, body mass index comorbidity-matched controls were enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments. FINDINGS: At 2-3 months from disease-onset, 64% of patients experienced breathlessness and 55% reported fatigue. On MRI, abnormalities were seen in lungs (60%), heart (26%), liver (10%) and kidneys (29%). Patients exhibited changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domains. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance were significantly reduced. The extent of extra-pulmonary MRI abnormalities and exercise intolerance correlated with serum markers of inflammation and acute illness severity. Patients had a higher burden of self-reported symptoms of depression and experienced significant impairment in all domains of quality of life compared to controls (p<0.0001 to 0.044). INTERPRETATION: A significant proportion of patients discharged from hospital reported symptoms of breathlessness, fatigue, depression and had limited exercise capacity. Persistent lung and extra-pulmonary organ MRI findings are common in patients and linked to inflammation and severity of acute illness. FUNDING: NIHR Oxford and Oxford Health Biomedical Research Centres, British Heart Foundation Centre for Research Excellence, UKRI, Wellcome Trust, British Heart Foundation.

Diagnostic yield and accuracy in a tertiary referral syncope unit validating the ESC guideline on syncope: a prospective cohort study.

AIMS: To assess in patients with transient loss of consciousness the diagnostic yield, accuracy, and safety of the structured approach as described in the ESC guidelines in a tertiary referral syncope unit. METHODS AND RESULTS: Prospective cohort study including 264 consecutive patients (≥18 years) referred with at least one self-reported episode of transient loss of consciousness and presenting to the syncope unit between October 2012 and February 2015. The study consisted of three phases: history taking (Phase 1), autonomic function tests (AFTs) (Phase 2), and after 1.5-year follow-up with assessment by a multidisciplinary committee (Phase 3). Diagnostic yield was assessed after Phases 1 and 2. Empirical diagnostic accuracy was measured for diagnoses according to the ESC guidelines after Phase 3. The diagnostic yield after Phase 1 (history taking) was 94.7% (95% CI: 91.1-97.0%, 250/264 patients) and increased to 97.0% (93.9-98.6%, 256/264 patients) after Phase 2. The overall diagnostic accuracy (as established in Phase 3) of the Phases 1 and 2 diagnoses was 90.6% (95% CI: 86.2-93.8%, 232/256 patients). No life-threatening conditions were missed. Three patients died, two unrelated to the cause of transient loss of consciousness, and one whom remained undiagnosed. CONCLUSION: A clinical work-up at a tertiary syncope unit using the ESC guidelines has a high diagnostic yield, accuracy, and safety. History taking (Phase 1) is the most important diagnostic tool. Autonomic function tests never changed the Phase 1 diagnosis but helped to increase the certainty of the Phase 1 diagnosis in many patients and yield additional diagnoses in patients who remained undiagnosed after Phase 1. Diagnoses were inaccurate in 9.4%, but no serious conditions were missed. This is adequate for clinical practice.

The value of septal rebound stretch analysis for the prediction of volumetric response to cardiac resynchronization therapy.

AIMS: Patient selection for cardiac resynchronization therapy (CRT) may be enhanced by evaluation of systolic myocardial stretching. We evaluate whether systolic septal rebound stretch (SRSsept) derived from speckle tracking echocardiography is a predictor of reverse remodelling after CRT and whether it holds additive predictive value over the simpler visual dyssynchrony assessment by apical rocking (ApRock). METHODS AND RESULTS: The association between SRSsept and change in left ventricular end-systolic volume (ΔLVESV) at 6 months of follow-up was assessed in 200 patients. Subsequently, the additive predictive value of SRSsept over the assessment of ApRock was evaluated in patients with and without left bundle branch block (LBBB) according to strict criteria. SRSsept was independently associated with ΔLVESV (ß 0.221, P = 0.002) after correction for sex, age, ischaemic cardiomyopathy, QRS morphology and duration, and ApRock. A high SRSsept (≥optimal cut-off value 2.4) also coincided with more volumetric responders (ΔLVESV ≥ -15%) than low SRSsept in the entire cohort (70.0% and 56.4%), in patients with strict LBBB (83.3% vs. 56.7%, P = 0.024), and non-LBBB (70.7% vs. 46.3%, P = 0.004). Moreover, in non-LBBB patients, SRSsept held additional predictive information over the assessment of ApRock alone since patients that showed ApRock and high SRSsept were more often volumetric responder than those with ApRock but low SRSsept (82.8% vs. 47.4%, P = 0.001). CONCLUSION: SRSsept is strongly associated with CRT-induced reduction in left ventricular end-systolic volume and holds additive prognostic information over QRS morphology and ApRock. Our data suggest that CRT patient selection may be improved by assessment of SRSsept, especially in the important subgroup without strict LBBB. CLINICAL TRIAL REGISTRATION: The MARC study was registered at clinicaltrials.gov: NCT01519908.

A Symmetric Prior for the Regularisation of Elastic Deformations: Improved anatomical plausibility in nonlinear image registration.

Nonlinear registration is critical to many aspects of Neuroimaging research. It facilitates averaging and comparisons across multiple subjects, as well as reporting of data in a common anatomical frame of reference. It is, however, a fundamentally ill-posed problem, with many possible solutions which minimise a given dissimilarity metric equally well. We present a regularisation method capable of selectively driving solutions towards those which would be considered anatomically plausible by penalising unlikely lineal, areal and volumetric deformations. This penalty is symmetric in the sense that geometric expansions and contractions are penalised equally, which encourages inverse-consistency. We demonstrate that this method is able to significantly reduce local volume changes and shape distortions compared to state-of-the-art elastic (FNIRT) and plastic (ANTs) registration frameworks. Crucially, this is achieved whilst simultaneously matching or exceeding the registration quality of these methods, as measured by overlap scores of labelled cortical regions. Extensive leveraging of GPU parallelisation has allowed us to solve this highly computationally intensive optimisation problem while maintaining reasonable run times of under half an hour.