40 research outputs found
Molecular Mechanisms of Myocardial Hypertrophy and Heart Failure : Experimental Studies on Cardiac G Protein-Coupled Receptor Signaling with Emphasis on Endothelin-1
Lege og forsker Thomas Gero von Lueder har i sitt doktorgradsarbeid funnet nye mekanismer bak hjertesvikt, og identifisert nye potensielle mÄl for behandling. Forekomsten av hjertesvikt Þker betydelig i hele den vestlige hemisfÊren, og pÄfÞrer samfunnet enorme kostnader. Hjertesvikt er en uhelbredelig tilstand som kjennetegnes ved at hjertemuskelens evne til Ä pumpe blod blir svekket, f.eks etter et hjerteinfarkt. Leveutsikten ved hjertesvikt er redusert pÄ linje med alvorlig kreftsykdom, selv med de mest moderne medisiner. Man antar at kroniske endringer i signalsystemer som endrer hjertets muskelmasse, pumpekraft og slagfrekvens over tid spiller en viktig rolle. I sin avhandling "Molecular Mechanisms of Myocardial Hypertrophy and Heart Failure ; Experimental studies on cardiac G protein-coupled receptor signalling with emphasis on endothelin-1" har Thomas Gero von Lueder og medarbeidere studert slike omdannelsesprosesser i hjertet, sÄkalt remodellering. Som en av flere involverte hormonsystemer er plasmanivÄer av endothelin-1 betydelig Þkt ved hjertesvikt, og gruppen kunne nÄ i en grisemodell fastslÄ at lungene er den viktigste endothelin-1 kilde. I et oppfÞlgende arbeid ble betennelsesceller i lungenene (makrofager) som har evne til endothelin-1 produksjon hemmet. Hemming av makrofager reduserte endothelin-1 nivÄer og bedret hjertefunksjon hos rotter med alvorlig hjertesvikt. Signalstoffer som adrenalin innvirker pÄ hjertet via mottagermolekyler (receptorer). Effekten slas av etter kort tid av enyzmer kalt GRK. Transgene mus der denne "bryter" funksjon via enzymet GRK3 var blokkert hadde styrket hjertefunksjon sammenlignet med normale kontrollmus. GRK3 hemming fÞrte dessuten til at musene tolererte kraftig og langvarig overbelastning pÄ hjertet mye bedre, og var beskyttet mot utvikling av hjertesvikt. Avhandlingen har fÞrt til Þkt kunnskap om Ärsaksforhold ved hjertesvikt og samtidig identifisert en rekke nye potensielle angrepspunkter for bedret behandling
Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction:An individual patient-level analysis of double-blind randomized trials
Aims: Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEFââ„â50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials. Methods and results: Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3âyears median follow-up, with an intention-to-treat analysis. For 14â262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21-33%), including 575 patients with LVEF 40-49% and 244ââ„â50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except for those in the small subgroup with LVEFââ„â50%. For LVEF 40-49%, death occurred in 21/292 [7.2%] randomized to beta-blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.34-1.03]. Cardiovascular death occurred in 13/292 [4.5%] with beta-blockers and 26/283 [9.2%] with placebo; adjusted HR 0.48 (95% CI 0.24-0.97). Over a median of 1.0âyears following randomization (nâ=â4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEFââ„50%. For patients in atrial fibrillation at baseline (nâ=â3050), beta-blockers increased LVEF whenâ<â50% at baseline, but did not improve prognosis. Conclusion: Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEFâ<â40%, but similar benefit was observed in the subgroup of patients with LVEF 40-49%
The Prognostic Role of Serum Uric Acid (SUA) in Coronary Artery Disease: PerSUAsive Data Plea for a Large Morbidity-Mortality Trial
International audienc
Left ventricular biomechanics in professional football players
Chronic exercise induces adaptive changes of left ventricular (LV) ejection and filling capacities which may be detected by novel speckleâtracking echocardiography (STE) and tissue Doppler imaging (TDI)âbased techniques. A total of 103 consecutive male elite Norwegian soccer players and 46 ageâmatched healthy controls underwent echocardiography at rest. STE was used to assess LV torsional mechanics and LV systolic longitudinal strain (LS). Diastolic function was evaluated by transâmitral blood flow, mitral annular velocities by TDI, and LV inflow propagation velocity by color Mâmode. Despite similar global LS, players displayed lower basal wall and higher apical wall LS values vs controls, resulting in an incremental baseâtoâapex gradient of LS. Color Mâmode and TDIâderived data were similar in both groups. Peak systolic twist rate (TWR) was significantly lower in players (86.4±2.8 vs controls 101.9±5.2 deg/s, P<.01). Diastolic untwisting rate (UTWR) was higher in players (â124.5±4.2 vs â106.9±6.7 deg/s) and peaked earlier during the cardiac cycle (112.7±0.8 vs 117.4±2.4% of systole duration, both P<.05). Untwisting/twisting ratio (â1.48±0.05 vs â1.11±0.08; P<.001) and untwisting performance (=UTR/TW; â9.25±0.34 vs â7.38±0.40 sâ1, P<.01) were increased in players. Augmented diastolic wall strain (DWS), a novel measure of LV compliance in players, was associated with improved myocardial mechanical efficiency. The described myocardial biomechanics may underlie augmented exertional cardiac function in athletes and may have a potential role to characterize athleteâČs heart by itself or to distinguish it from hypertensive or hypertrophic cardiomyopathy
Cardiac Dimensions and Function are not Altered among Females with the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition associated with several negative health outcomes. A hallmark of ME/CFS is decreased exercise capacity and often profound exercise intolerance. The causes of ME/CSF and its related symptoms are unknown, but there are indications of a dysregulated metabolism with impaired glycolytic vs oxidative energy balance. In line with this, we recently demonstrated abnormal lactate accumulation among ME/CFS patients compared with healthy controls after exercise testing. Here we examined if cardiac dimensions and function were altered in ME/CFS, as this could lead to increased lactate production. Methods: We studied 16 female ME/CFS patients and 10 healthy controls with supine transthoracic echocardiography, and we assessed cardiac dimensions and function by conventional echocardiographic and Doppler analysis as well as novel tissue Doppler and strain variables. Results: A detailed analyses of key variables of cardiac dimensions and cardiac function revealed no significant differences between the two study groups. Conclusion: In this cohort of well-described ME/CFS patients, we found no significant differences in echocardiographic variables characterizing cardiac dimensions and function compared with healthy controls
Prediction of extreme wind events by utilisation of a weather-type Extreme Forecast Index - Part I: Early warnings of extreme wind events utilizing DWD objective weather type classification & ECMWF Ensemble Prediction System Extreme Forecast Index
Late Pseudoaneurysm After Access Site Closure with Manta in Transfemoral Aortic Valve Implantation
Introduction: Access site vascular complications in transfemoral transcatheter aortic valve implantation (TF-TAVI) are still a major concern. Recently, a novel collagen plug based closure device (Manta) was introduced. The results from the first reports on Manta are very promising, but not much is known about the long-term patency. Report: A case of late pseudoaneurysm after access site arterial closure with Manta in TF-TAVI is described. The patient presented five weeks after left sided TF-TAVI with pain and claudication like symptoms in the left leg. CT angiography revealed a pseudoaneurysm at the puncture site. The patient was successfully treated by vascular surgery. Discussion: The results from recent peri-operative reports on the Manta vascular closure device (VCD) are promising, but not much is known about the long-term patency. In the present report a patient is described who developed a pseudoaneurysm several weeks after access site closure with Manta. To the authorsâ knowledge, no such late access site complications after use of the Manta VCD have been reported previously. Keywords: TAVI, Access site closure, Manta, Pseudoaneurys