Citations

Czech physiologist Penaz tried to overcome limitations of invasive pulse-contour methods (PCM) in clinical applications by a non-invasive method (finger mounted BP cuff) for continuous arterial waveform detection and beat-to-beat analysis. This discovery resulted in significant interest in human physiology and non-invasive examination of hemodynamic parameters, however has limitations because of the distal BP recording using a volume-clamp method. Thus, we propose a validation of beat-to-beat signal analysis acquired by novel a brachial occlusion-cuff (suprasystolic) principle and signal obtained from Finapres during a forced expiratory effort against an obstructed airway (Valsalva maneuver). Twelve healthy adult subjects [2 females, age = (27.2 ± 5.1) years] were in the upright siting position, breathe through the mouthpiece (simultaneously acquisition by brachial blood pressure monitor and Finapres) and at a defined time were asked to generate positive mouth pressure for 20 s (Valsalva). For the purpose of signal analysis, we proposed parameter a “Occlusion Cuff Index” (OCCI). The assumption about similarities between measured signals (suprasystolic brachial pulse waves amplitudes and Finapres’s MAP) were proved by averaged Pearson’s correlation coefficient (r- = 0.60, p < 0.001). The averaged Pearson’s correlation coefficient for the comparative analysis of OCCI between methods was r- = 0.88, p < 0.001. The average percent change of OCCI during maneuver: 8% increase, 19% decrease and percent change of max/min ratio is 35%. The investigation of brachial pulse waves measured by novel brachial blood pressure monitor shows positive correlation with Finapres and the parameter OCCI shows promise as an index, which could describe changes during beat-to-beat cardiac cycles.

Background: Acute myocarditis is an inflammatory condition that may herald the onset of dilated cardiomyopathy (DCM) or arrhythmogenic cardiomyopathy (ACM). We investigated the frequency and clinical consequences of DCM and ACM genetic variants in a population-based cohort of patients with acute myocarditis. Methods: This was a population-based cohort of 336 consecutive patients with acute myocarditis enrolled in London and Maastricht. All participants underwent targeted DNA sequencing for well-characterized cardiomyopathy-associated genes with comparison to healthy controls (n=1053) sequenced on the same platform. Case ascertainment in England was assessed against national hospital admission data. The primary outcome was all-cause mortality. Results: Variants that would be considered pathogenic if found in a patient with DCM or ACM were identified in 8% of myocarditis cases compared with <1% of healthy controls ( P =0.0097). In the London cohort (n=230; median age, 33 years; 84% men), patients were representative of national myocarditis admissions (median age, 32 years; 71% men; 66% case ascertainment), and there was enrichment of rare truncating variants (tv) in ACM-associated genes (3.1% of cases versus 0.4% of controls; odds ratio, 8.2; P =0.001). This was driven predominantly by DSP -tv in patients with normal LV ejection fraction and ventricular arrhythmia. In Maastricht (n=106; median age, 54 years; 61% men), there was enrichment of rare truncating variants in DCM-associated genes, particularly TTN -tv, found in 7% (all with left ventricular ejection fraction <50%) compared with 1% in controls (odds ratio, 3.6; P =0.0116). Across both cohorts over a median of 5.0 years (interquartile range, 3.9–7.8 years), all-cause mortality was 5.4%. Two-thirds of deaths were cardiovascular, attributable to worsening heart failure (92%) or sudden cardiac death (8%). The 5-year mortality risk was 3.3% in genotype-negative patients versus 11.1% for genotype-positive patients ( P adjusted =0.08). Conclusions: We identified DCM- or ACM-associated genetic variants in 8% of patients with acute myocarditis. This was dominated by the identification of DSP -tv in those with normal left ventricular ejection fraction and TTN -tv in those with reduced left ventricular ejection fraction. Despite differences between cohorts, these variants have clinical implications for treatment, risk stratification, and family screening. Genetic counseling and testing should be considered in patients with acute myocarditis to help reassure the majority while improving the management of those with an underlying genetic variant.

Abstract In the following brief report, we highlight the advances in the neuro-oncology space from the ASCO 2022 Annual Meeting. We put into context the phase 2 and 3 trials and how these may alter the standard of care going forward. In addition, we highlight some other earlier work that will lead to future and potentially practice-changing trials.

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P &amp;lt; .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P &amp;lt; .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P &amp;lt; .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Zusammenfassung Hintergrund Die Brustrekonstruktion mittels autologem Gewebe ist fester Bestandteil eines ganzheitlichen Therapiekonzeptes bei Patientinnen mit Mammakarzinom. Während zahlreiche Studien den körperlichen und psychischen Gesundheitszustand von Patientinnen mit Brustkrebs nach Mastektomie und konsekutiver Brustrekonstruktion untersuchen, mangelt es an objektiven Daten zur Beurteilung des Einflusses von Ablatio und Brustrekonstruktion auf die Wahrnehmung von externen Beobachtern. Diese Studie untersucht die Blickmuster bei Betrachtung einer Brust in verschiedenen Stadien der Brustrekonstruktion mittels DIEP Lappenplastik. Material und Methoden Mittels Eye-Tracking-Technologie wurden die Augenbewegungen von 58 Studienteilnehmer*in- nen beim Betrachten von 2D-Fotografien einer Patientin in den verschiedenen Stadien der Brustrekonstruktion (1. Ablatio, 2. Aufbau mittels DIEP Lappenplastik, 3. MAK Rekonstruktion) analysiert. Die Zeit bis zur ersten Fixierung und die Dauer der Fixierung wurde in jedem Bild für die rechte und linke Brust aufgezeichnet. Ergebnisse Die Dauer der kompletten Fixierung der operierten Brust zeigte über die verschiedenen Stadien der Brustrekonstruktion insgesamt eine signifikante Abnahme mit p<0,001. Gleichzeitig zeigte sich keine statistisch signifikante Veränderung der Blickdauer auf der nicht-operierten Gegen- seite mit p=0,174. Die Zeit bis zur ersten Blickfixierung der betroffenen Brust zeigte eine signifikante Zunahme über die verschiedenen Rekonstruktionsschritte, mit p<0,001. Bei der Gegenseite zeigte sich kein statistisch signifikanter Unterschied in der Zeit bis zur ersten Fixierung, mit p=0,344. Schlussfolgerung Die Ablatio mammae und die einzelnen Schritte der Brustrekonstruktion verändern die äußerliche Wahrnehmung von Patientinnen. Im Laufe der einzelnen re- konstruktiven Teilschritte kommt es zu einer zunehmenden Aufhebung der Blickdeviation in Richtung erkrankte Brust.

Background: Myocarditis may predispose to dilated cardiomyopathy (DCM) and sudden cardiac death (SCD). Familial data indicate a potential genetic susceptibility shared with arrhythmogenic cardiomyopathy (ACM). We present the first large-scale genotype-phenotype study of adults with acute myocarditis. Methods: A cohort comprising 336 consecutive patients with acute myocarditis was enrolled in London and Maastricht. All participants underwent targeted DNA sequencing for well-characterised cardiomyopathy-associated genes. The burden of rare protein altering variants (PAV) in ACM genes, DCM genes, and TTN specifically, were compared with local healthy controls sequenced on the same platform (n=1053). Case ascertainment was assessed against national hospital admission data. Results: We identified rare protein-altering variants in 23% of cases compared to 16% in controls (Δ+6.8%; p=0.021), with rare truncating variants (tv) in 6% of cases compared to <1% of controls ((Δ+5%; p=0.0097). In London (n=230; median left ventricular ejection fraction (LVEF) 63%), which was representative of national myocarditis admissions, 4.8% of cases carried rare tv, particularly within ACM genes (3% cases vs 0% controls; odds ratio 8.2; p=0.001). This was predominantly driven by desmoplakin (DSP)-tv in patients with normal LVEF. In Maastricht (n=106; median LVEF 30%), rare tv in DCM genes were enriched, particularly TTN-tv found in 7% (all with LVEF<50%) compared to 1% in controls (OR 3.6; p=0.0116). During a median follow-up of 1.9 years, all-cause mortality was greatest in those with a DCM variant (18% vs 4% with no variant; OR 5.0; p=0.004). Conclusion: We identified enrichment of cardiomyopathy gene variants in acute myocarditis patients, dominated by DSP-tv in those with normal LVEF and TTN-tv in those with reduced LVEF. Incorporation of genetic testing may be beneficial to identify such high-risk individuals and guide family screening in acute myocarditis patients.

Background: The epicardial adipose tissue (EAT) has been identified as a sensitive marker of cardiometabolic risk. Recent evidence suggests efficacy of long-term statin therapy in reducing the EAT in patients with coronary artery disease. Whether the volume of EAT changes in patients with atrial fibrillation (AF) treated with a statin for a short time period is currently unknown. Methods: A population of AF patients undergoing pulmonary vein isolation was randomized to receive either 80 mg/day of atorvastatin (n=51, 44 males, age 55±10 years) or placebo (n=51, 41 males, age 56±10) for a 3 month period. EAT volume was assessed by cardiac computed tomography at baseline and after 3-month follow-up. Results: Patients randomized to statin treatment exhibited significant decreases in EAT volume (baseline vs follow-up: 105.8 ± 52.95 vs 103.05 ± 52.55 cm3, p = 0.05), C-reactive protein (2.97 ± 4.3 mg/L vs 2.03 ± 2.2 mg/L, p < 0.05), total cholesterol (182.5 ± 36.9 vs 129.3 ± 40.6 mg/dL, p < 0.001), and low density lipoprotein-cholesterol (111.88 ± 28 vs 61 ± 32.6 mg/dL, p < 0.001) at follow-up, while the body mass index did not vary (29.42 ± 5.2 vs 29.11 ± 4.8 kg/m2, p = 0.28). No changes were seen in the placebo group. Conclusions: Short-term high-dose statin therapy significantly reduced the volume of EAT in AF patients. EAT volume modulation might be an important mechanism by which statins may influence cardiovascular risk.

Objective With a growing appreciation for interindividual anatomical variability and patient‐specific brain connectivity, advanced imaging sequences offer the opportunity to directly visualize anatomical targets for deep brain stimulation (DBS). The lack of quantitative evidence demonstrating their clinical utility, however, has hindered their broad implementation in clinical practice. Methods Using fast gray matter acquisition T1 inversion recovery (FGATIR) sequences, the present study identified a thalamic hypointensity that holds promise as a visual marker in DBS. To validate the clinical utility of the identified hypointensity, we retrospectively analyzed 65 patients (26 female, mean age = 69.1 ± 12.7 years) who underwent DBS in the treatment of essential tremor. We characterized its neuroanatomical substrates and evaluated the hypointensity's ability to predict clinical outcome using stimulation volume modeling and voxelwise mapping. Finally, we determined whether the hypointensity marker could predict symptom improvement on a patient‐specific level. Results Anatomical characterization suggested that the identified hypointensity constituted the terminal part of the dentatorubrothalamic tract. Overlap between DBS stimulation volumes and the hypointensity in standard space significantly correlated with tremor improvement ( R 2 = 0.16, p = 0.017) and distance to hotspots previously reported in the literature ( R 2 = 0.49, p = 7.9e‐4). In contrast, the amount of variance explained by other anatomical atlas structures was reduced. When accounting for interindividual neuroanatomical variability, the predictive power of the hypointensity increased further ( R 2 = 0.37, p = 0.002). Interpretation Our findings introduce and validate a novel imaging‐based marker attainable from FGATIR sequences that has the potential to personalize and inform targeting and programming in DBS for essential tremor. ANN NEUROL 2022;91:613–628

Abstract Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale &gt;2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men – women) = −0.295 (90% highest posterior density interval = −0.556 to −0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level.