Impact of left ventricular ejection fraction and aortic valve gradient on mortality following transcatheter aortic valve intervention.

BACKGROUND: Data regarding the impact of reduced left ventricular ejection fraction (LVEF) and/or reduced mean aortic valve gradient (AVG) on outcomes following transcatheter aortic valve intervention (TAVI) have been conflicting. We sought to assess the relationship between LVEF, AVG, and 1-year mortality in patients undergoing TAVI. METHODS: We prospectively evaluated 298 consecutive adults undergoing TAVI from 2015 to 2018 at an academic tertiary medical center. Patients were categorized according to LVEF and mean AVG. The primary outcome of interest was all-cause mortality at 1 year. RESULTS: Of 298 adults undergoing TAVI, 66 (22.1%) had baseline LVEF ≤45% while 232 (77.9%) had baseline LVEF >45%; 173 (58.1%) had baseline AVG < 40mmHg while 125 (41.9%) had baseline AVG ≥ 40mmHg. Rates of 1-year all-cause mortality were significantly higher in patients with LVEF ≤45% (28.8% vs 12.1%, p = 0.001) and those with AVG < 40mmHg (19.7% vs 10.4%, p = 0.031) compared to those with LVEF >45% and AVG ≥ 40mmHg respectively. In multivariable analysis, higher AVG (per mmHg) (OR 0.97, 95% CI 0.94-0.99, p = 0.026) was noted to be independently associated with lower rates of 1-year mortality, while LVEF was not (OR 0.98, 95% CI 0.96-1.01). CONCLUSIONS: In this prospective, contemporary registry of adults undergoing TAVI, while 1-year unadjusted mortality rates are significantly higher in patients with reduced LVEF and reduced AVG, risk-adjusted mortality at 1 year is only higher in those with reduced AVG - not in those with reduced LVEF.

Transcatheter aortic valve replacement in heart failure.

Patients with severe aortic stenosis (AS) may develop heart failure (HF), the presence of which has traditionally been deemed as a final stage in AS progression with poor outcomes. The use of transcatheter aortic valve replacement (TAVR) has become the preferred therapy for most patients with AS and concomitant HF. With its instant afterload reduction, TAVR offers patients with HF significant haemodynamic benefits, with corresponding changes in left ventricular structure and improved mortality and quality of life. The prognostic covariates and optimal timing of TAVR in patients with less than severe AS remain unclear. The purpose of this review is to describe the association between TAVR and outcomes in patients with HF, particularly in the setting of left ventricular systolic dysfunction, acute HF, and right ventricular systolic dysfunction, and to highlight areas for future research.

The role of structured inpatient lipid protocols in optimizing non-statin lipid lowering therapy: a review and single-center experience.

Dyslipidemia is a leading contributor to atherosclerotic cardiovascular disease (ASCVD). There has been a significant improvement in the treatment of dyslipidemia in the past 10 years with the development of new pharmacotherapies. The intent of this review is help enhance clinicians understanding of non-statin lipid lowering therapies in accordance with the 2022 American College of Cardiology Expert Consensus Clinical Decision Pathway on the Role of Non-statin Therapies for LDL-Cholesterol Lowering. We also present a single-center experience implementing a systematic inpatient protocol for lipid lowering therapy for secondary prevention of ASCVD.

Structural correlates of survival in progressive supranuclear palsy.

INTRODUCTION: Many studies of the Richardson's syndrome phenotype of progressive supranuclear palsy (PSP) have elucidated regions of progressive atrophy and neural correlates of clinical severity. However, the neural correlates of survival and how these differ according to variant phenotypes are poorly understood. We set out to identify structural changes that predict severity and survival from scanning date to death. METHODS: Structural magnetic resonance imaging data from 112 deceased people with clinically defined 'probable' or 'possible' PSP were analysed. Neuroanatomical regions of interest volumes, thickness and area were correlated with 'temporal stage', defined as the ratio of time from symptom onset to death, time from scan to death ('survival from scan'), and in a subset of patients, clinical severity, adjusting for age and total intracranial volume. Forty-nine participants had post mortem confirmation of the diagnosis. RESULTS: Using T1-weighted magnetic resonance imaging, we confirmed the midbrain, and bilateral cortical structural correlates of contemporary disease severity. Atrophy of the striatum, cerebellum and frontotemporal cortex correlate with temporal stage and survival from scan, even after adjusting for severity. Subcortical structure-survival relationships were stronger in Richardson's syndrome than variant phenotypes. CONCLUSIONS: Although the duration of PSP varies widely between people, an individual's progress from disease onset to death (their temporal stage) reflects atrophy in striatal, cerebellar and frontotemporal cortical regions. Our findings suggest magnetic resonance imaging may contribute to prognostication and stratification of patients with heterogenous clinical trajectories and clarify the processes that confer mortality risk in PSP.

Standardized Definitions for Cardiogenic Shock Research and Mechanical Circulatory Support Devices: Scientific Expert Panel From the Shock Academic Research Consortium (SHARC).

The Shock Academic Research Consortium is a multi-stakeholder group, including representatives from the US Food and Drug Administration and other government agencies, industry, and payers, convened to develop pragmatic consensus definitions useful for the evaluation of clinical trials enrolling patients with cardiogenic shock, including trials evaluating mechanical circulatory support devices. Several in-person and virtual meetings were convened between 2020 and 2022 to discuss the need for developing the standardized definitions required for evaluation of mechanical circulatory support devices in clinical trials for cardiogenic shock patients. The expert panel identified key concepts and topics by performing literature reviews, including previous clinical trials, while recognizing current challenges and the need to advance evidence-based practice and statistical analysis to support future clinical trials. For each category, a lead (primary) author was assigned to perform a literature search and draft a proposed definition, which was presented to the subgroup. These definitions were further modified after feedback from the expert panel meetings until a consensus was reached. This manuscript summarizes the expert panel recommendations focused on outcome definitions, including efficacy and safety.

Predictive Contribution of the Superficial Neck Muscles to Short-Latency Rate of Force Development of the Head and Neck.

PURPOSE: To evaluate the contribution of splenius capitis, sternocleidomastoid, and upper fibers of trapezius activation to the gains in rate of force development (RFD) of the head and neck during maximum voluntary ballistic contractions. METHODS: RFD gain was facilitated by a single-session intervention for maximum voluntary ballistic contractions in the anterior direction, oriented at 45° to the midsagittal plane, which require active restraint of axial rotation. Muscle activation for the agonist (sternocleidomastoid) and 2 antagonists (splenius capitis and upper fibers of trapezius) was evaluated. The study sample included 12 physically active men (mean age, 22.6 y). RFD (N·m·s-1; 0-100 ms) and integrated muscle activity (50 ms before and 100 ms after force onset) were measured at 10 minutes, 20 minutes, and 2 days postintervention, relative to baseline. Muscle activation predictive of RFD gains was evaluated by linear regression analysis. RFD reproducibility was evaluated using the coefficient of variation of the typical error. RESULTS: The intervention yielded a 1.95- to 2.39-fold RFD gain (P ≤ .05), with greater RFD gain for participants with a lower peak moment of force (<10.9 N·m) than those with a higher peak moment (≥10.9 N·m) at baseline (P ≤ .002). For the low group, 65% to 74% of the RFD gain was predicted by ipsilateral sternocleidomastoid activation, with ipsilateral splenius capitis activation predicting 77% to 92% of RFD gain for the high group. Absolute peak and impulse of static force were greater for the high than for the low group (P ≤ .04). RFD reproducibility was high (coefficient of variation of the typical error ≤ 14.4%). CONCLUSIONS: The agonist- and antagonist-focused synergies might reflect different functional priorities, higher RFD gain compared with higher head-neck force.

Network connectivity and structural correlates of survival in progressive supranuclear palsy and corticobasal syndrome.

There is a pressing need to understand the factors that predict prognosis in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), with high heterogeneity over the poor average survival. We test the hypothesis that the magnitude and distribution of connectivity changes in PSP and CBS predict the rate of progression and survival time, using datasets from the Cambridge Centre for Parkinson-plus and the UK National PSP Research Network (PROSPECT-MR). Resting-state functional MRI images were available from 146 participants with PSP, 82 participants with CBS, and 90 healthy controls. Large-scale networks were identified through independent component analyses, with correlations taken between component time series. Independent component analysis was also used to select between-network connectivity components to compare with baseline clinical severity, longitudinal rate of change in severity, and survival. Transdiagnostic survival predictors were identified using partial least squares regression for Cox models, with connectivity compared to patients' demographics, structural imaging, and clinical scores using five-fold cross-validation. In PSP and CBS, between-network connectivity components were identified that differed from controls, were associated with disease severity, and were related to survival and rate of change in clinical severity. A transdiagnostic component predicted survival beyond demographic and motion metrics but with lower accuracy than an optimal model that included the clinical and structural imaging measures. Cortical atrophy enhanced the connectivity changes that were most predictive of survival. Between-network connectivity is associated with variability in prognosis in PSP and CBS but does not improve predictive accuracy beyond clinical and structural imaging metrics.

Varicella zoster virus cerebellitis without skin manifestations in an immunocompetent adult.

The varicella zoster virus (VZV) is a ubiquitous, neurotropic pathogen capable of reactivation from sensory ganglion cells to cause dermatomal herpes zoster infection, alongside a range of pathologies within the central nervous system. The presence of VZV cerebellitis without skin manifestations, however, is exceedingly rare in immunocompetent adults.We report a case of VZV cerebellitis in an immunocompetent woman in her 70s, in the absence of a rash. The patient presented with a 2-week history of progressive gait ataxia, headache and mild confusion. Serological tests and neuroimaging were unremarkable. Diagnosis was confirmed through cerebrospinal fluid (CSF) analysis which revealed lymphocytosis and the presence of VZV DNA on PCR analysis. The patient showed symptomatic improvement following empirical acyclovir treatment, corroborated by favourable CSF analysis 10 days post-treatment initiation.Infective aetiology, including VZV, should be considered in patients presenting with acute cerebellar ataxia, even in immunocompetent adults with an absence of dermatological signs.

Temporal dynamics predict symptom onset and cognitive decline in familial frontotemporal dementia.

INTRODUCTION: We tested whether changes in functional networks predict cognitive decline and conversion from the presymptomatic prodrome to symptomatic disease in familial frontotemporal dementia (FTD). METHODS: For hypothesis generation, 36 participants with behavioral variant FTD (bvFTD) and 34 controls were recruited from one site. For hypothesis testing, we studied 198 symptomatic FTD mutation carriers, 341 presymptomatic mutation carriers, and 329 family members without mutations. We compared functional network dynamics between groups, with clinical severity and with longitudinal clinical progression. RESULTS: We identified a characteristic pattern of dynamic network changes in FTD, which correlated with neuropsychological impairment. Among presymptomatic mutation carriers, this pattern of network dynamics was found to a greater extent in those who subsequently converted to the symptomatic phase. Baseline network dynamic changes predicted future cognitive decline in symptomatic participants and older presymptomatic participants. DISCUSSION: Dynamic network abnormalities in FTD predict cognitive decline and symptomatic conversion. HIGHLIGHTS: We investigated brain network predictors of dementia symptom onset Frontotemporal dementia results in characteristic dynamic network patterns Alterations in network dynamics are associated with neuropsychological impairment Network dynamic changes predict symptomatic conversion in presymptomatic carriers Network dynamic changes are associated with longitudinal cognitive decline.

Position Statement on Vascular Access Safety for Percutaneous Devices in AMI Complicated by Cardiogenic Shock.

In the United States, the frequency of using percutaneous mechanical circulatory support devices for acute myocardial infarction complicated by cardiogenic shock is increasing. These devices require large-bore vascular access to provide left, right, or biventricular cardiac support, frequently under urgent/emergent circumstances. Significant technical and logistical variability exists in device insertion, care, and removal in the cardiac catheterization laboratory and in the cardiac intensive care unit. This variability in practice may contribute to adverse outcomes observed in centers that receive patients with cardiogenic shock, who are at higher risk for circulatory insufficiency, venous stasis, bleeding, and arterial hypoperfusion. In this position statement, we aim to: 1) describe the public health impact of bleeding and vascular complications in cardiogenic shock; 2) highlight knowledge gaps for vascular safety and provide a roadmap for a regulatory perspective necessary for advancing the field; 3) propose a minimum core set of process elements, or "vascular safety bundle"; and 4) develop a possible study design for a pragmatic trial platform to evaluate which structured approach to vascular access drives most benefit and prevents vascular and bleeding complications in practice.

The Effect of the FIFA 11 + with Added Neck Exercises on Maximal Isometric Neck Strength and Peak Head Impact Magnitude During Heading: A Pilot Study.

BACKGROUND: Higher neck strength has been postulated to reduce head impact magnitude during purposeful heading in football. OBJECTIVES: This pilot trial explored the effect of a neck exercise programme on (1) neck strength and (2) head impact magnitude during heading in male and female adolescent football players. METHODS: Boys and girls (aged 12-17 years) were randomised by team to the intervention (5 weeks of supervised neuromuscular neck exercises integrated into part 2 of the FIFA 11 + , completed three times per week) or the control group (usual part 2 of the FIFA 11 + , no neck exercises). Outcomes included isometric neck strength and head impact magnitude (peak linear acceleration and peak angular velocity) during standardised heading from a throw-in (at baseline and 6 weeks) plus completion of an evaluation survey by intervention players and coaches. RESULTS: In total, 52 players (n = 31 intervention; n = 21 control) completed the study. Mixed-model analysis of variance (ANOVA) revealed significant differences in neck strength variables (p < 0.001), peak linear acceleration (p = 0.04) and peak angular velocity (p = 0.04) between the intervention and control groups over time. Intervention players demonstrated increases in mean composite neck strength (53.8% intervention vs 15.6% control) as well as decreases in mean peak linear head acceleration during heading (- 11.8% vs - 5.0%) from baseline to follow-up. Reduction in peak angular velocity was more pronounced in girls (- 27.7%) than boys (- 11.5%) in the intervention group. The addition of neck exercises into part 2 of the FIFA 11 + was feasible and accepted by players and coaches. CONCLUSION: On average, players who completed neck exercises demonstrated an increase in isometric neck strength and a decrease in head impact magnitude during heading. These exercises were easily incorporated into usual training. Australian New Zealand Clinical Trials Registry (no: ACTRN12619001375145).