An investigator-sponsored pragmatic randomized controlled trial of AntiCoagulation vs AcetylSalicylic Acid after Transcatheter Aortic Valve Implantation: Rationale and design of ACASA-TAVI.

BACKGROUND: The optimal antithrombotic therapy after transcatheter aortic valve implantation (TAVI) is unknown. Bioprosthetic valve dysfunction (BVD) is associated with adverse outcomes and may be prevented by anticoagulation therapy. A dedicated randomized trial comparing monotherapy NOAC to single antiplatelet therapy has not been performed previously. We hypothesize that therapy with any anti-factor Xa NOAC will reduce BVD compared to antiplatelet therapy, without compromising safety. METHODS: ACASA-TAVI is a multicenter, prospective, randomized, open-label, blinded endpoint, all-comers trial comparing a monotherapy anti-factor Xa NOAC strategy (intervention arm) with a single antiplatelet therapy strategy (control arm) after successful TAVI. Three-hundred and sixty patients without indication for oral anticoagulation will be randomized in a 1:1 ratio to either apixaban 5 mg twice per day, edoxaban 60 mg daily, or rivaroxaban 20 mg daily for 12 months followed by acetylsalicylic acid 75 mg daily indefinitely, or to acetylsalicylic acid 75 mg daily indefinitely. The 2 co-primary outcomes are (1) incidence of Hypo-Attenuated Leaflet Thickening (HALT) on 4-dimensional cardiac CT at 12 months, and (2) a Safety Composite of VARC-3 bleeding events, thromboembolic events (myocardial infarction and stroke), and death from any cause, at 12 months. RESULTS: The first 100 patients had a mean age of 74 ± 3.6 years, 33% were female, the average body-mass index was 27.9 ± 4.4 kg/m2, and 15% were smokers. A balloon-expanded valve was used in 82% and a self-expandable valve in 18%. CONCLUSIONS: The trial is planned, initiated, funded, and conducted without industry involvement. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT05035277.

Safety and efficacy of hybrid vascular closure technique using both a suture- and collagen-mediated closure device after transfemoral transcatheter aortic valve implantation.

OBJECTIVES: To evaluate the clinical utility and feasibility of a hybrid technique for obtaining vascular hemostasis by combining a suture- and a collagen-mediated system after transfemoral transcatheter aortic valve implantation (TF TAVI) in a real-world setting. METHODS: In 75 consecutive TF TAVI procedures, we investigated a hybrid closing method to achieve hemostasis at the large bore puncture site using a combination of one presuture closure system (ProGlide) and one collagen-mediated system (Angio-Seal). Vascular complications at puncture site were recorded until discharge. RESULTS: Successful hemostasis by the hybrid technique was achieved in 74 out of 75 patients, and the method was well tolerated by all patients. In 73 patients, (97.3%) neither puncture site related complications nor serious early or late bleedings were observed during a median hospital stay of 2 days postprocedure. CONCLUSION: This single-center registry study indicates that a percutaneous hybrid closure technique is safe and efficacious in closing large bore arteriotomies. It is an easy and reliable technique that may contribute to simplifying TAVI procedures. STUDY REGISTRATION: The data was collected from an internal quality control registry on treatment of patients with valvular heart disease with or without coronary artery disease, No 2014/17280, Oslo University Hospital, Ullevål.

Left ventricular and proximal aorta coupling in magnetic resonance imaging: aging together?

The importance of aorta-ventricular coupling in cardiovascular disease is recognized but underestimated. The contribution of the age-related decline in ascending aortic function compared with characteristic impedance and total peripheral resistance on left ventricular function and remodeling is poorly studied. Our aim was to evaluate the relation of proximal aortic distensibility and impedance with left ventricular geometry and function in asymptomatic individuals. We prospectively studied 100 subjects (47 men, 53 women, age: 20-84 yr). Aortic strain, distensibility, arch pulse wave velocity, characteristic impedance (Zc), total peripheral resistance, left ventricular (LV) volumes and mass, wall stress, and peak global circumferential myocardial strain and strain rates were determined by MRI. Central pressures were measured from tonometry. Ea/Ev, an index of vascular-ventricular coupling, and LV wall stress were preserved across age- or aortic-stiffness-stratified groups. Static and pulsatile components of aortic load were differentially associated with age. Increased total vascular resistance was associated with decreased LV strain and increased concentric remodeling [ratio of LV mass to end-diastolic volume (M/V ratio)] in all individuals. In younger individuals (<45 yr), aortic distensibility was related to LV strain and concentric remodeling (M/V ratio), whereas Zc was related to LV strain and concentric remodeling (M/V ratio) in older individuals (>45 yr). Early age-related stiffening of the ascending aorta is a component of LV afterload subsequently associated with increased aortic impedance and alterations in LV geometry, namely concentric remodeling, decreased myocardial strain, and increased stroke work such that LV wall stress and arterial-ventricular coupling are preserved. NEW & NOTEWORTHY Local flow and deformation can both be assessed with high precision noninvasively in the ascending aorta using MRI. Combined with central pressure measurement, they provide distensibility and impedance and simultaneous reference assessment of left ventricular deformation and geometry, hence a comprehensive evaluation of arterial-ventricular coupling to study physiology and disease.

Catheter-based left atrial appendage closure. / Kateterbasert lukking av venstre atriums aurikkel.

BAKGRUNN: Atrieflimmer er en vanlig tilstand i befolkningen og gir økt risiko for hjerneslag. Antikoagulasjonsbehandling er effektivt for å forebygge tromboembolisme ved atrieflimmer, men av ulike grunner blir mange atrieflimmerpasienter med indikasjon for antikoagulasjonsbehandling ikke behandlet. Kateterbasert lukking av venstre atriums aurikkel er en ny metode for å forebygge hjerneslag ved atrieflimmer. MATERIALE OG METODE: I perioden september 2014-april 2016 gjennomgikk 27 pasienter med atrieflimmer og høy risiko for hjerneslag forsøk på kateterbasert lukking av venstre atriums aurikkel ved Oslo universitetssykehus. Antikoagulasjonsbehandling var vurdert som kontraindisert hos 26 av pasientene. Vi presenterer resultater fra prosedyre, ekkokardiografikontroller og kliniske hendelser i oppfølgingsperioden på ett år. RESULTATER: Aurikkelplugg ble vellykket implantert hos 26 pasienter. To pasienter fikk komplikasjoner i forbindelse med prosedyren: En fikk hjerneslag og en fikk transfusjonskrevende lyskeblødning. En pasient fikk hjertetamponade fem måneder etter prosedyren. En pasient som grunnet anatomisk vanskelige forhold ikke fikk implantert aurikkelplugg, døde av hjerneslag i oppfølgingsperioden. Tre pasienter hadde klinisk transitorisk iskemisk anfall (TIA). Det var ingen forekomst av intrakranial eller gastrointestinal blødning. FORTOLKNING: Kateterbasert lukking av venstre atriums aurikkel er gjennomførbart, men innebærer risiko for komplikasjoner og bør forbeholdes pasienter med høy risiko for hjerneslag og kontraindikasjon mot antikoagulasjonsbehandling.

Myocardial strain imaging: how useful is it in clinical decision making?

Myocardial strain is a principle for quantification of left ventricular (LV) function which is now feasible with speckle-tracking echocardiography. The best evaluated strain parameter is global longitudinal strain (GLS) which is more sensitive than left ventricular ejection fraction (LVEF) as a measure of systolic function, and may be used to identify sub-clinical LV dysfunction in cardiomyopathies. Furthermore, GLS is recommended as routine measurement in patients undergoing chemotherapy to detect reduction in LV function prior to fall in LVEF. Intersegmental variability in timing of peak myocardial strain has been proposed as predictor of risk of ventricular arrhythmias. Strain imaging may be applied to guide placement of the LV pacing lead in patients receiving cardiac resynchronization therapy. Strain may also be used to diagnose myocardial ischaemia, but the technology is not sufficiently standardized to be recommended as a general tool for this purpose. Peak systolic left atrial strain is a promising supplementary index of LV filling pressure. The strain imaging methodology is still undergoing development, and further clinical trials are needed to determine if clinical decisions based on strain imaging result in better outcome. With this important limitation in mind, strain may be applied clinically as a supplementary diagnostic method.

Left atrial structure and functional quantitation using cardiovascular magnetic resonance and multimodality tissue tracking: validation and reproducibility assessment.

BACKGROUND: Left atrium (LA) strain, volume and function are important markers of cardiovascular disease and myocardial impairment. We aimed to assess the accuracy of LA biplane volume and function measured by Multimodality Tissue Tracking (MTT). Also we assessed the inter-study reproducibility for cardiovascular magnetic resonance (CMR) derived LA volume and function parameters. METHODS: Thirty subjects (mean age: 71.3 ± 8.7, 87% male) including twenty subjects with cardiovascular events and ten healthy subjects, with CMR were evaluated in the Multi-Ethnic Study of Atherosclerosis (MESA). LA volumes were computed by the modified biplane method from 2- and 4-chamber projections and the Simpson's method from short-axis slices using both methods - manual and semi-automated delineation using MTT. LA total, active and passive ejection fractions were calculated. Pearson's correlation and Bland-Altman analysis were used to compare the measurements. In a second sample of 25 subjects (age: 65.7 ± 7.1, 72% males) inter study, intra and inter reader reliability analysis was performed. The intra-class correlation coefficient (ICC) was evaluated. RESULTS: Left atrial MTT structural and functional parameters were not different from manual delineation, yet image analysis was only half as time consuming on average with MTT. Maximal volume MTT was not different between the Simpson's and Biplane methods, functional parameters, however were different. MTT allowed us to measure multiple LA parameters with good-excellent (ICC; 0.88- 0.98, p < 0.001) intra-and inter reader reproducibility and fair-good (ICC; 0.44-0.82, p < 0.05-0.001) inter study reproducibility. CONCLUSIONS: MTT derived LA biplane volume and function is accurate and reproducible and is suited for use in longitudinal studies.

Strain, strain rate, torsion, and twist: echocardiographic evaluation.

Deformation imaging by tissue Doppler imaging (TDI) and speckle-tracking echocardiography (STE) are emerging clinical methods. TDI- and STE-derived parameters, such as myocardial strain and strain rate, as well as torsion and twist, provide detailed information about myocardial function and are associated with cardiovascular morbidity and mortality. However, only echocardiographic laboratories with experience in deformation imaging have included these methods in daily clinical practice. In this review, we describe myocardial deformation parameters and relevant echocardiographic methods and address recent developments in the clinical application of deformation imaging.

Prognostic value of myocardial circumferential strain for incident heart failure and cardiovascular events in asymptomatic individuals: the Multi-Ethnic Study of Atherosclerosis.

AIMS: Left ventricular (LV) circumferential strain (Ecc) is a sensitive index of regional myocardial function. Currently, no studies have assessed its prognostic value in general population. We sought to investigate whether Ecc has a prognostic value for predicting incident heart failure (HF) and other major cardiovascular events in asymptomatic individuals without a history of previous cardiovascular diseases. METHODS AND RESULTS: We, prospectively, assessed incident HF and atherosclerotic events during a 5.5 ± 1.3-year period in 1768 asymptomatic individuals aged 45-84 (mean age 65 years; 47% female) who underwent tagged magnetic resonance imaging for strain determination. During the follow-up period, 39 (2.2%) participants experienced incident HF and 108 (6.1%) participants had atherosclerotic cardiovascular events. Average of peak Ecc of 12-LV segments (Ecc-global) and mid-slice (Ecc-mid) was -17.0 ± 2.4 and -17.5 ± 2.7%, respectively. Participants with average absolute Ecc-mid lower than -16.9% had a higher cumulative hazard of incident HF (log-rank test, P = 0.001). In cox regression analysis, Ecc-mid predicted incident HF independent of age, diabetes status, hypertension, interim myocardial infarction, LV mass index, and LV ejection fraction (hazard ratio 1.15 per 1%, 95% CI: 1.01-1.31, P = 0.03). This relationship remained significant after adjustment for LV-end-systolic wall stress into covariates. In addition, by adding Ecc-mid to risk factors, LV ejection fraction, and the LV mass index, both the global χ(2) value (76.6 vs. 82.4, P = 0.04) and category-less net-reclassification index (P = 0.01, SE = 0.18, z = 2.53) were augmented for predicting HF. Circumferential strain was also significantly related to the composite atherosclerotic cardiovascular events, but its relationship was attenuated after introducing the LV mass index. CONCLUSION: Circumferential shortening provides robust, independent, and incremental predictive value for incident HF in asymptomatic subjects without any history of previous clinical cardiovascular disease. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00005487.

Myocardial relaxation, restoring forces, and early-diastolic load are independent determinants of left ventricular untwisting rate.

BACKGROUND: Peak left ventricular (LV) untwisting rate (UTR) has been introduced as a clinical marker of diastolic function. This study investigates if early-diastolic load and restoring forces are determinants of UTR in addition to the rate of LV relaxation. METHODS AND RESULTS: In 10 anesthetized dogs we measured UTR by sonomicrometry and speckle tracking echocardiography at varying LV preloads, increased contractility, and myocardial ischemia. UTR was calculated as the time derivative of LV twist. Because preload modified end-diastolic twist, LV systolic twist was calculated in absolute terms with reference to the end-diastolic twist configuration at baseline. Relaxation rate was measured as the time constant (τ) of LV isovolumic pressure decay. Early-diastolic load was measured as LV pressure at the time of mitral valve opening. Circumferential-longitudinal shear strain was used as an index of restoring forces. In a multivariable mixed model analysis a strong association was observed between UTR and LV pressure at the time of mitral valve opening (parameter estimate [ß]=6.9; P<0.0001), indicating an independent effect of early-diastolic load. Furthermore, the associations between UTR and circumferential-longitudinal shear strain (ß=-11.3; P<0.0001) and τ (ß=-1.6, P<0.003) were consistent with independent contributions from restoring forces and rate of relaxation. Maximal UTR before mitral valve opening, however, was determined only by relaxation rate and restoring forces. CONCLUSIONS: The present study indicates that early-diastolic load, restoring forces, and relaxation rate are independent determinants of peak UTR. However, only relaxation rate and restoring forces contributed to UTR during isovolumic relaxation.

A novel clinical method for quantification of regional left ventricular pressure-strain loop area: a non-invasive index of myocardial work.

AIMS: Left ventricular (LV) pressure-strain loop area reflects regional myocardial work and metabolic demand, but the clinical use of this index is limited by the need for invasive pressure. In this study, we introduce a non-invasive method to measure LV pressure-strain loop area. METHODS AND RESULTS: Left ventricular pressure was estimated by utilizing the profile of an empiric, normalized reference curve which was adjusted according to the duration of LV isovolumic and ejection phases, as defined by timing of aortic and mitral valve events by echocardiography. Absolute LV systolic pressure was set equal to arterial pressure measured invasively in dogs (n = 12) and non-invasively in patients (n = 18). In six patients, myocardial glucose metabolism was measured by positron emission tomography (PET). First, we studied anaesthetized dogs and observed an excellent correlation (r = 0.96) and a good agreement between estimated LV pressure-strain loop area and loop area by LV micromanometer and sonomicrometry. Secondly, we validated the method in patients with various cardiac disorders, including LV dyssynchrony, and confirmed an excellent correlation (r = 0.99) and a good agreement between pressure-strain loop areas using non-invasive and invasive LV pressure. Non-invasive pressure-strain loop area reflected work when incorporating changes in local LV geometry (r = 0.97) and showed a strong correlation with regional myocardial glucose metabolism by PET (r = 0.81). CONCLUSIONS: The novel non-invasive method for regional LV pressure-strain loop area corresponded well with invasive measurements and with directly measured myocardial work and it reflected myocardial metabolism. This method for assessment of regional work may be of clinical interest for several patients groups, including LV dyssynchrony and ischaemia.

High-sensitivity C-reactive protein as an independent predictor of progressive myocardial functional deterioration: the multiethnic study of atherosclerosis.

BACKGROUND: Systemic inflammation has been linked to the development of heart failure in population studies including Multi-Ethnic Study of Atherosclerosis (MESA), but little evidence exists regarding potential mechanism of this relationship. In this study, we used longitudinal magnetic resonance imaging follow-up analysis to examine whether C-reactive protein (CRP) levels relate to progressive myocardial functional deterioration as a potential mechanism of incident heart failure. METHODS: Regional myocardial functional data from MESA participants who had baseline CRP measurement and also underwent tagged cardiac magnetic resonance imaging both at baseline and at 5-year follow-up were analyzed. Left ventricular midwall and midslice peak circumferential strain (Ecc), of which a more negative value denotes stronger regional myocardial function, was measured. Circumferential strain change was calculated as the difference between baseline and follow-up Ecc. RESULTS: During the follow-up period, participants (n = 785) with elevated CRP experienced a decrease in strain, independent of age, gender, and ethnicity (B = 0.081, ∆Ecc change per 1 mg/L CRP change, 95% CI 0.036-0.126, P < .001, model 1) and, additionally, beyond systolic blood pressure, heart rate, diabetes, smoking status, body mass index, current medication, and glomerular filtration rate (B = 0.099, 0.052-0.145, P < .001, model 2). The relationship remained statistically significant after further adjustment for left ventricular mass, coronary calcium score, and interim clinical coronary events (B = 0.098, 0.049-0.147, P < .001, model 3). CONCLUSION: Higher CRP levels are related to progressive myocardial functional deterioration independent of subclinical atherosclerosis and clinical coronary events in asymptomatic individuals without previous history of heart disease.

Interleukin-6 inhibition in ST-elevation myocardial infarction: Immune cell profile in the randomised ASSAIL-MI trial.

BACKGROUND: We recently showed that interleukin (IL)-6 inhibition by tocilizumab improves myocardial salvage in ST-elevation myocardial infarction (STEMI). However, the mechanisms for this effect are not clear. METHODS: In this exploratory sub-study of the ASSAIL-MI trial, we examined leukocyte differential counts and their relation to myocardial salvage and peak troponin T (TnT) in STEMI patients randomised to tocilizumab (n = 101) or placebo (n = 98). We performed RNA-sequencing on whole blood (n = 40) and T cells (n = 20). B and T cell subpopulations were examined by flow cytometry (n = 69). FINDINGS: (i) STEMI patients had higher neutrophil counts at hospitalisation compared with stable angina patients. (ii) After percutaneous coronary intervention there was a gradual decline in neutrophils, which was significantly more pronounced in the tocilizumab group. (iii) The decrease in neutrophils in the tocilizumab group was associated with improved myocardial salvage and lower peak TnT. (iv) RNA-sequencing suggested that neutrophil function was also attenuated by tocilizumab. (v) B and T cell sub-populations changed only minimally after STEMI with minor effects of tocilizumab, supported as well by RNA-sequencing analyses of T cells. (vi) However, a low CD8+ count was associated with improved myocardial salvage in patients admitted to the hospital > 3 h after symptom onset. INTERPRETATION: Tocilizumab induced a rapid reduction in neutrophils and seemed to attenuate neutrophil function in STEMI patients potentially related to the beneficial effects of tocilizumab on myocardial salvage. FUNDING: South-Eastern Norway Regional Health Authority (Nos. 2019067, 2017084), the Central Norway Regional Health Authority and Norwegian Research Council (No. 283867).

Mechanics of left ventricular relaxation, early diastolic lengthening, and suction investigated in a mathematical model.

We investigated the determinants of ventricular early diastolic lengthening and mechanics of suction using a mathematical model of the left ventricle (LV). The model was based on a force balance between the force represented by LV pressure (LVP) and active and passive myocardial forces. The predicted lengthening velocity (e') from the model agreed well with measurements from 10 dogs during 5 different interventions (R = 0.69, P < 0.001). The model showed that e' was increased when relaxation rate and systolic shortening increased, when passive stiffness was decreased, and when the rate of fall of LVP during early filling was decreased relative to the rate of fall of active stress. We first defined suction as the work the myocardium performed to pull blood into the ventricle. This occurred when contractile active forces decayed below and became weaker than restoring forces, producing a negative LVP. An alternative definition of suction is filling during falling pressure, commonly believed to be caused by release of restoring forces. However, the model showed that this phenomenon also occurred when there had been no systolic compression below unstressed length and therefore in the absence of restoring forces. In conclusion, relaxation rate, LVP, systolic shortening, and passive stiffness were all independent determinants of e'. The model generated a suction effect seen as lengthening occurring during falling pressure. However, this was not equivalent with the myocardium performing pulling work on the blood, which was performed only when restoring forces were higher than remaining active fiber force, corresponding to a negative transmural pressure.

Mechanism of prolonged electromechanical delay in late activated myocardium during left bundle branch block.

During left bundle branch block (LBBB), electromechanical delay (EMD), defined as time from regional electrical activation (REA) to onset shortening, is prolonged in the late-activated left ventricular lateral wall compared with the septum. This leads to greater mechanical relative to electrical dyssynchrony. The aim of this study was to determine the mechanism of the prolonged EMD. We investigated this phenomenon in an experimental LBBB dog model (n = 7), in patients (n = 9) with biventricular pacing devices, in an in vitro papillary muscle study (n = 6), and a mathematical simulation model. Pressures, myocardial deformation, and REA were assessed. In the dogs, there was a greater mechanical than electrical delay (82 ± 12 vs. 54 ± 8 ms, P = 0.002) due to prolonged EMD in the lateral wall vs. septum (39 ± 8 vs.11 ± 9 ms, P = 0.002). The prolonged EMD in later activated myocardium could not be explained by increased excitation-contraction coupling time or increased pressure at the time of REA but was strongly related to dP/dt at the time of REA (r = 0.88). Results in humans were consistent with experimental findings. The papillary muscle study and mathematical model showed that EMD was prolonged at higher dP/dt because it took longer for the segment to generate active force at a rate superior to the load rise, which is a requirement for shortening. We conclude that, during LBBB, prolonged EMD in late-activated myocardium is caused by a higher dP/dt at the time of activation, resulting in aggravated mechanical relative to electrical dyssynchrony. These findings suggest that LV contractility may modify mechanical dyssynchrony.

Is radial artery occlusion and local vascular complications following transradial coronary procedures affected by the type of haemostasis device used? A non-inferiority Randomized Controlled Trial (RadCom trial).

AIMS: Vascular access site complications following transradial coronary procedures are less common and severe compared to femoral approach. Radial artery occlusion is considered the main adverse effect. As radial access is gaining more acknowledgement, complication awareness, and understanding is important. The aim was to assess complication rates following transradial coronary procedures and to compare two radial compression devices in a non-inferiority randomized controlled trial. METHODS AND RESULTS: Four hundred and ninety-nine patients were randomized to radial compression with a new device (RY Stop, n = 248) or the reference device (TR Band, n = 251) following transradial coronary procedures. Radial artery occlusion persistent at 90 days was the primary endpoint. Discomfort and accounts of vascular complications at access site were secondary endpoints. Radial artery occlusion was observed in 5% (n = 26) for the entire cohort with no difference between groups (RY Stop 6% vs. TR Band 5%; P = 0.69). Patients overall reported low levels of discomfort and the median scores were similar in both groups; RY Stop: 7 vs. TR Band: 10 (P = 0.90). There were few incidents of bleeding (7%), however, they were significantly more frequent with the RY Stop (12%) than with the TR Band (3%; P = 0.001). Few patients (4%) developed access site haematomas, and the incidence was similar in the two groups (P = 0.98). CONCLUSION: We observed a radial artery occlusion rate of 5% at 90 days post-procedure. Access site discomfort and vascular complication rates were low. Overall, the RY Stop compression device was not inferior to the TR Band except occurrences of bleeding.

Randomized Trial of Interleukin-6 Receptor Inhibition in Patients With Acute ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Prompt myocardial revascularization with percutaneous coronary intervention (PCI) reduces infarct size and improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI). However, as much as 50% of the loss of viable myocardium may be attributed to the reperfusion injury and the associated inflammatory response. OBJECTIVES: This study sought to evaluate the effect of the interleukin-6 receptor inhibitor tocilizumab on myocardial salvage in acute STEMI. METHODS: The ASSAIL-MI trial was a randomized, double-blind, placebo-controlled trial conducted at 3 high-volume PCI centers in Norway. Patients admitted with STEMI within 6 h of symptom onset were eligible. Consenting patients were randomized in a 1:1 fashion to promptly receive a single infusion of 280 mg tocilizumab or placebo. The primary endpoint was the myocardial salvage index as measured by magnetic resonance imaging after 3 to 7 days. RESULTS: We randomized 101 patients to tocilizumab and 98 patients to placebo. The myocardial salvage index was larger in the tocilizumab group than in the placebo group (adjusted between-group difference 5.6 [95% confidence interval: 0.2 to 11.3] percentage points, p = 0.04). Microvascular obstruction was less extensive in the tocilizumab arm, but there was no significant difference in the final infarct size between the tocilizumab arm and the placebo arm (7.2% vs. 9.1% of myocardial volume, p = 0.08). Adverse events were evenly distributed across the treatment groups. CONCLUSIONS: Tocilizumab increased myocardial salvage in patients with acute STEMI. (ASSessing the effect of Anti-IL-6 treatment in Myocardial Infarction [ASSAIL-MI]; NCT03004703).

Determinants of left ventricular early-diastolic lengthening velocity: independent contributions from left ventricular relaxation, restoring forces, and lengthening load.

BACKGROUND: Peak early-diastolic mitral annulus velocity (e') by tissue Doppler imaging has been introduced as a clinical marker of diastolic function. This study investigates whether lengthening load (early-diastolic load) and restoring forces are determinants of e' in addition to rate of left ventricular (LV) relaxation. METHODS AND RESULTS: In 10 anesthetized dogs, we measured e' by sonomicrometry and tissue Doppler imaging during baseline, volume loading, caval constriction, dobutamine infusion, and occlusion of the left anterior descending coronary artery. Relaxation was measured as the time constant (tau) of LV pressure decay by micromanometer. Lengthening load was measured as LV transmural pressure at mitral valve opening (LVP(MVO)). Restoring forces were quantified by 2 different indices: (1) As the difference between minimum and unstressed LV diameter (Lmin-L0) and (2) as the estimated fully relaxed LV transmural pressure (FRP(Est)) at minimum diameter. In the overall analysis, a strong association was observed between e' and LVP(MVO) (beta=0.49; P<0.001), which indicates an independent effect of lengthening load, as well as between e' and Lmin-L0 (beta=-0.38; P<0.002) and between e' and FRP(Est) (beta=-0.31; P<0.002), consistent with an independent contribution of restoring forces. A direct effect of rate of relaxation on e' was observed in a separate analysis of baseline, dobutamine, and ischemia when postextrasystolic beats were included (beta=-0.06, P<0.01). CONCLUSIONS: The present study indicates that in the nonfailing ventricle, in addition to LV relaxation, restoring forces and lengthening load are important determinants of early-diastolic lengthening velocity.

Suicidal intention, psychosocial factors and referral to further treatment: a one-year cross-sectional study of self-poisoning.

BACKGROUND: Patients treated for self-poisoning have an increased risk of death, both by natural and unnatural causes. The follow-up of these patients is therefore of great importance. The aim of this study was to explore the differences in psychosocial factors and referrals to follow-up among self-poisoning patients according to their evaluated intention. METHODS: A cross-sectional multicenter study of all 908 admissions to hospital because of self-poisoning in Oslo during one year was completed. Fifty-four percent were females, and the median age was 36 years. The patients were grouped according to evaluated intention: suicide attempts (moderate to high suicide intent), appeals (low suicide intent) and substance-use related poisonings. Multinomial regression analyses compared patients based on their evaluated intention; suicide attempts were used as the reference. RESULTS: Of all self-poisoning incidents, 37% were suicide attempts, 26% were appeals and 38% were related to substance use. Fifty-five percent of the patients reported previous suicide attempts, 58% reported previous or current psychiatric treatment and 32% reported daily substance use. Overall, patients treated for self-poisoning showed a lack of social integration. Only 33% were employed, 34% were married or cohabiting and 53% were living alone. Those in the suicide attempt and appeal groups had more previous suicide attempts and reported more psychiatric treatment than those with poisoning related to substance use. One third of all patients with substance use-related poisoning reported previous suicide attempts, and one third of suicide attempt patients reported daily substance use. Gender distribution was the only statistically significant difference between the appeal patients and suicide attempt patients. Almost one in every five patients was discharged without any plans for follow-up: 36% of patients with substance use-related poisoning and 5% of suicide attempt patients. Thirty-eight percent of all suicide attempt patients were admitted to a psychiatric ward. Only 10% of patients with substance use-related poisoning were referred to substance abuse treatment. CONCLUSIONS: All patients had several risk factors for suicidal behavior. There were only minor differences between suicide attempt patients and appeal patients. If the self-poisoning was evaluated as related to substance use, the patient was often discharged without plans for follow-up.

Mechanisms of preejection and postejection velocity spikes in left ventricular myocardium: interaction between wall deformation and valve events.

BACKGROUND: Normal left ventricular myocardium demonstrates distinct spikes in the velocity trace before and after left ventricular ejection. We tested the hypothesis that the preejection and postejection velocity spikes reflect early systolic shortening and late systolic lengthening that are interrupted by mitral and aortic valve closure, respectively. METHODS AND RESULTS: In 11 anesthetized dogs, timing of valve closure was determined by pressure variables; left ventricular dimensions were determined by sonomicrometry. Myocardial shortening started 20+/-10 ms (mean+/-SD; P<0.001) before mitral valve closure and was interrupted at the time of mitral valve closure (time difference, 4+/-7 ms). Similarly, myocardial lengthening started 31+/-15 ms (P<0.001) before aortic valve closure and was interrupted at the time of aortic valve closure (time difference, 0+/-3 ms). Prevention of mitral (n=4) and aortic (n=4) valve closure by stenting the valves abolished the preejection and postejection velocity spikes, respectively. Echocardiographic measurements of patients (n=15) with severe mitral regurgitation showed that the preejection velocity spike was reduced after prosthetic valve replacement (43+/-25 versus 32+/-15 mm/s; P=0.036), indicating that preejection shortening was larger with a leaking valve. Similarly, late systolic lengthening was reduced in patients (n=15) with severe aortic regurgitation after prosthetic valve replacement; minimum postejection velocity spike was increased from -32+/-11 to -17+/-11 mm/s; P=0.0003). Asynchronous onset of contraction/relaxation and atrioventricular interaction were investigated as alternative mechanisms of the velocity spikes in dogs and patient groups but were found implausible. CONCLUSIONS: This study supports the hypothesis that normal left ventricular preejection and postejection velocity spikes are attributed to valve closures that interrupt early systolic shortening and late systolic lengthening, respectively.