• Stougaard Kirkland opublikował 1 rok, 3 miesiące temu

    05). All components of LAS and LA strain rate showed proportional impairment with increasing probability of HFpEF (all p<0.05). Out of the speckle tracking-derived parameters, reservoir LAS showed the largest area under the curve (AUC=0.78, p<0.001) and the strongest independent predictive value (OR 1.22, 95% CI 1.08-1.38) to identify patients with high probability of HFpEF.

    Reservoir LAS shows a high diagnostic performance to distinguish HFpEF from non-cardiac causes of dyspnea in symptomatic patients with paroxysmal AF.

    Reservoir LAS shows a high diagnostic performance to distinguish HFpEF from non-cardiac causes of dyspnea in symptomatic patients with paroxysmal AF.

    Left ventricular (LV) systolic dysfunction and myocardial fibrosis have prognostic implications in repaired tetralogy of Fallot (rTOF), but their relationship with myocardial strain is not well understood. We evaluated systolic strain and fibrosis (extracellular volume fraction, ECV) of the left ventricle (LV) using feature tracking with magnetic resonance and determine their association with each other and clinical outcome.

    Adults with rTOF and age-matched controls underwent CMR to measure LV-ECV. Feature-tracking was used to quantify radial, circumferential, and longitudinal strain in both 2 and 3 dimensions. Clinical events (death, arrhythmia and heart-failure hospitalization) were obtained through chart review. Associations between strain, ECV and clinical events were explored.

    48 rTOF subjects (age 40.5±14.3, 42% female) and 20 healthy controls were included. Both LV 2D and 3D global circumferential strain (GCS) and global longitudinal strain (GLS) were lower in rTOF subjects (p≤0.01 for all). There was no association between strain and LV-ECV. Strain parameters correlated with ventricular volumes and function. After a median follow-up of 8.5years (range 1-10.9years) there were 5 deaths, 6 hospitalizations and 9 new arrhythmias. By multivariate Cox-regression, GLS was an independent predictor of both hospitalization and death, whereas LV-ECV was an independent predictor of arrhythmia.

    While both LV strain abnormalities and fibrosis are present in rTOF, they are associated with different types of clinical outcome, and not to each other. The findings suggest that these measures reflect different long-term adverse adaptations to abnormal hemodynamics.

    While both LV strain abnormalities and fibrosis are present in rTOF, they are associated with different types of clinical outcome, and not to each other. The findings suggest that these measures reflect different long-term adverse adaptations to abnormal hemodynamics.

    Screening strategies to diagnose previously undetected atrial fibrillation (AF), especially silent AF (SAF), in at-risk populations may help reduce the number of strokes. We prospectively assessed the incidence rate of AF, including SAF, using an automated AF-detection capable sphygmomanometer in the General Practitioner (GP) setting.

    This was a population-based prospective study of unselected general population of ≥65years without prior AF. Participating GPs were requested, in the period February 2018-April 2019, to record all AF diagnoses including those derived from the AF-detection capable sphygmomanometer and confirmed by 12‑lead ECG or ECG Holter in asymptomatic patients.

    Overall, 14,987 patients assisted by 76 GPs accumulated 16,838 patient-years of follow up. The incidence rate of AF was 2.25% patient-years (95%CI 2.03-2.48). AF was more frequently detected in male, older, overweight, and patients with prior stroke, congestive heart failure, and chronic kidney disease. One in four patients had device-detected SAF (0.56% patient-years, 95%CI 0.46-0.69). Age, overweight, and the number of annual visits, were independent predictors of both SAF and AF. In addition, congestive heart failure, mitral valve disease were independent predictors of AF. Due to the interaction between blood pressure and age the risk of AF increased exponentially after 75years of age in patients with higher systolic blood pressure values.

    We found a higher than previously reported incidence rate of AF possibly by capturing SAF. Our simple protocol might be feasible in large-scale screening for AF and SAF in routine GP care.

    We found a higher than previously reported incidence rate of AF possibly by capturing SAF. Our simple protocol might be feasible in large-scale screening for AF and SAF in routine GP care.

    Although the 0/1h high-sensitivity cardiac troponin T (0/1 hs-cTnT) algorithm and many risk scores have been validated for use in emergency departments (EDs), their utility in high-acuity ED patients has not been validated. We aimed to validate the 0/1 hs-cTnT algorithm and the HEART, TIMI, GRACE, T-MACS and NOTR risk scores before and after combining the 0/1 algorithm in high-acuity ED chest pain patients.

    A prospective observational study was conducted in the high-acuity ED of Siriraj Hospital, a tertiary hospital in Bangkok, Thailand. Adult patients with chest pain were enrolled between November 2018 and November 2019. The primary outcome was 30-day major adverse cardiac events (30-day MACE), defined as a composite of mortality, acute myocardial infarction, significant coronary stenosis and revascularization procedures.

    Of 350 recruited patients, 59 (16.9%) developed 30-day MACE. For the 0/1 hs-cTnT algorithm, sensitivity and negative predictive value (NPV) were 91.3% (95%CI 79.2-97.6%) and 97.2% (95%CI 93.2-98.9%), respectively. Specificity and positive predictive value were 79.6% (95%CI 72.8-85.2%) and 53.9% (95%CI 46.2-61.3%), respectively. Of the risk scores, the HEART score had the highest area under the receiver operator characteristic curve (0.74 [95%CI 0.68-0.81]). Combining the 0/1 hs-cTnT algorithm, a TIMI score cut-off of ≤1 had the best sensitivity and NPV (both 100%) and identified the greatest proportion of patients (24.3%) suitable for safe discharge.

    The 0/1 hs-cTnT algorithm may be feasible in Asian high-acuity ED patients. The HEART score outperformed other scores in predicting 30-day MACE. Combining the 0/1 hs-cTnT algorithm with a TIMI cut-off score≤1had the best rule-out performance.

    The 0/1 hs-cTnT algorithm may be feasible in Asian high-acuity ED patients. The HEART score outperformed other scores in predicting 30-day MACE. Combining the 0/1 hs-cTnT algorithm with a TIMI cut-off score ≤ 1 had the best rule-out performance.Background – Variants within the alpha-tropomyosin gene (TPM1) cause dominantly inherited cardiomyopathies, including dilated (DCM), hypertrophic (HCM) and restrictive (RCM) cardiomyopathy. Here we investigated whether TPM1 variants observed in DCM and HCM patients affect cardiomyocyte physiology differently. Methods – We identified a large family with DCM carrying a recently identified TPM1 gene variant (T201M) and a child with RCM with compound heterozygote TPM1 variants (E62Q and M281T) whose family members carrying single variants show diastolic dysfunction and HCM. The effects of TPM1 variants (T201M, E62Q or M281T) and of a plasmid containing both the E62Q and M281T variants on single-cell Ca2+ transients (CaT) in HL-1 cardiomyocytes were studied. To define toxic threshold levels, we performed dose-dependent transfection of TPM1 variants. In addition, cardiomyocyte structure was studied in human cardiac biopsies with TPM1 variants. Results – Overexpression of TPM1 variants led to time-dependent progressive deterioration of CaT, with the smallest effect seen for E62Q and larger and similar effects seen for the T201M and M281T variants. Overexpression of E62Q/M281T did not exacerbate the effects seen with overexpression of a single TPM1 variant. T201M (DCM) replaced endogenous tropomyosin dose-dependently, while M281T (HCM) did not. Human cardiac biopsies with TPM1 variants revealed loss of sarcomeric structures. Conclusion – All TPM1 variants result in reduced cardiomyocyte CaT amplitudes and loss of sarcomeric structures. These effects may underlie pathophysiology of different cardiomyopathy phenotypes.Complex experimental studies of vertebrate host, vector, and parasite interactions are essential in understanding virulence, but are difficult or impossible to conduct if vector species are unknown. Subinoculation of erythrocytic meronts of avian malarial parasites into susceptible hosts can avoid this problem, but this approach omits early exoerythrocytic stages, e.g. cryptozoites and metacryptozoites, that normally develop from sporozoites. A fundamental question that has remained unanswered is whether blood stage and sporozoite-induced malarial infections lead to differences in the dynamics of parasitemia in acute infections, patterns of parasite development, and host mortality. Here we demonstrate in a Carduelis spinus – Plasmodium relictum (genetic lineage pSGS1) system that experimental infections using inoculation of infected blood and using mosquito bite show similar peaks of parasitemias, but some measures of parasite development in the vertebrate host differ. Infected birds from all groups show decreased activity during the peak of parasitemia. There is no doubt that experimental infections using vectors provide the most precise information about the development of a parasite and its virulence in the host, but experimental infections using blood stages demonstrate similar parasitemias and effects on the host. These results are important for further experimental research of malarial parasites, especially studying avian Plasmodium parasites with unknown vectors.Toxoplasma gondii has a worldwide distribution and infects virtually all warm-blooded animals, including humans. Ingestion of the environmentally resistant oocyst stage, excreted only in the feces of cats, is central to transmission of this apicomplexan parasite. There is vast literature on the host and T. gondii tachyzoite (proliferative stage of the parasite) but little is known of the host-parasite interaction and conversion of the free-living stage (sporozoite inside the oocyst) to the parasitic stage. Here, we present events that follow invasion of host cells with T. gondii sporozoites by using immunofluorescence (IF) and transmission electron microscopy (TEM). Several human type cell cultures were infected with T. gondii sporozoites of the two genotypes (Type II, ME49 and Type III, VEG) most prevalent worldwide. For the first known time, using anti-rhoptry neck protein 4 (RON4) antibodies, the moving junction was visualized in sporozoites during the invasion process and shortly after its completion. Surprisingly, IF and TEM evaluation revealed that intracellular sporozoites release, at their posterior end, long membranous tails, herein named sporozoite-specific trails (SSTs). Differential permeabilization and IF experiments showed that the SSTs are associated with several dense granule proteins (GRAs) and that their membranous component is of parasite origin. Furthermore, TEM observations demonstrated that SST-associated sporozoites are delimited by a typical parasitophorous vacuole, which is retained during parasite exit from the host cell and during cell-to-cell passage. Our data strongly suggest that host cell traversal by T. gondii sporozoites relies on a novel force-producing mechanism, based on the massive extrusion at the parasite posterior pole of GRA-associated membranous material derived from the same pool of membranes forming the intravacuolar network.

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