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  • 1
    Online Resource
    Online Resource
    Resonant Acoustic Rheometry to Measure Coagulation Kinetics in Hemophilia A and Healthy Plasma: A Novel Viscoelastic Method
    Georg Thieme Verlag KG ; 2023
    In:  Seminars in Thrombosis and Hemostasis Vol. 49, No. 02 ( 2023-03), p. 201-208
    Details
    In: Seminars in Thrombosis and Hemostasis, Georg Thieme Verlag KG, Vol. 49, No. 02 ( 2023-03), p. 201-208
    Abstract: Compared with conventional coagulation tests and factor-specific assays, viscoelastic hemostatic assays (VHAs) can provide a more thorough evaluation of clot formation and lysis but have several limitations including clot deformation. In this proof-of-concept study, we test a noncontact technique, termed resonant acoustic rheometry (RAR), for measuring the kinetics of human plasma coagulation. Specifically, RAR utilizes a dual-mode ultrasound technique to induce and detect surface oscillation of blood samples without direct physical contact and measures the resonant frequency of the surface oscillation over time, which is reflective of the viscoelasticity of the sample. Analysis of RAR results of normal plasma allowed defining a set of parameters for quantifying coagulation. RAR detected a flat-line tracing of resonant frequency in hemophilia A plasma that was corrected with the addition of tissue factor. Our RAR results captured the kinetics of plasma coagulation and the newly defined RAR parameters correlated with increasing tissue factor concentration in both healthy and hemophilia A plasma. These findings demonstrate the feasibility of RAR as a novel approach for VHA, providing the foundation for future studies to compare RAR parameters to conventional coagulation tests, factor-specific assays, and VHA parameters.
    Type of Medium: Online Resource
    ISSN: 0094-6176 , 1098-9064
    URL: Article
    DOI: 10.1055/s-0042-1757896
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2023
    detail.hit.zdb_id: 2072469-X
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  • 2
    Online Resource
    Online Resource
    Co‐formulation of ketoprofen with tulathromycin alters pharmacokinetic and pharmacodynamic profile of ketoprofen in cattle
    Wiley ; 2022
    In:  Journal of Veterinary Pharmacology and Therapeutics Vol. 45, No. 1 ( 2022-01), p. 69-82
    Details
    In: Journal of Veterinary Pharmacology and Therapeutics, Wiley, Vol. 45, No. 1 ( 2022-01), p. 69-82
    Abstract: The current studies aimed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) profile and to establish a PK‐PD model for ketoprofen in a new fixed combination product containing tulathromycin (2.5 mg/kg) and ketoprofen (3 mg/kg) to treat bovine respiratory disease associated with pyrexia in cattle. Firstly, the effect of different ketoprofen doses as mono‐substance (1, 3, and 6 mg/kg subcutaneous) on lipopolysaccharide‐induced fever was evaluated which indicated that rectal temperature reduction lasted longer in the calves receiving 3 and 6 mg/kg ketoprofen. Secondly, the PK profile of the combination product was compared with mono‐substance products (3 mg/kg subcutaneous and intramuscular). The PK profile of ketoprofen in the combination product was characterized by longer t 1/2 , lower C max and increased AUC in comparison with mono‐substance products. Due to prolonged ketoprofen exposure in the combination product, the pyrexia reducing effect of the combination product lasted longer in a second lipopolysaccharide challenge study in comparison with mono‐substance products. Finally, a PK‐PD model for the anti‐pyretic effect of ketoprofen was developed based on the data from the different studies. The PK‐PD model eliminated the need for additional animal experiments and indicated that a 3 mg/kg ketoprofen dose in the combination product provided optimal efficacy.
    Type of Medium: Online Resource
    ISSN: 0140-7783 , 1365-2885
    URL: Issue
    URL: Article
    DOI: 10.1111/jvp.v45.1
    DOI: 10.1111/jvp.12999
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2023924-5
    SSG: 22
    SSG: 15,3
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  • 3
    Online Resource
    Online Resource
    Greyzone myocardial fibrosis and ventricular arrhythmias in patients with a left ventricular ejection fraction 〉35%
    Oxford University Press (OUP) ; 2022
    In:  EP Europace Vol. 24, No. 1 ( 2022-01-04), p. 31-39
    Details
    In: EP Europace, Oxford University Press (OUP), Vol. 24, No. 1 ( 2022-01-04), p. 31-39
    Abstract: To determine whether myocardial fibrosis and greyzone fibrosis (GZF) on cardiovascular magnetic resonance (CMR) is associated with ventricular arrhythmias in patients with coronary artery disease (CAD) and a left ventricular ejection fraction (LVEF) & gt;35%. Methods and results In this retrospective study of CAD patients, GZF mass using the 3SD method (GZF3SD) and total fibrosis mass using the 2SD method (TF2SD) on CMR were assessed in relation to the primary, combined endpoint of sudden cardiac death, ventricular tachycardia, ventricular fibrillation, or resuscitated cardiac arrest. Among 701 patients [age: 65.8 ± 12.3 years (mean ± SD)], 28 (3.99%) patients met the primary endpoint over 5.91 years (median; interquartile range 4.42–7.64). In competing risks analysis, a GZF3SD mass ≥5.0 g was strongly associated with the primary endpoint [subdistribution hazard ratio (sHR): 17.4 (95% confidence interval, CI 6.64–45.5); area under receiver operator characteristic curve (AUC): 0.85, P  & lt; 0.001]. A weaker association was observed for TF2SD mass ≥23 g [sHR 10.4 (95% CI 4.22–25.8); AUC: 0.80, P  & lt; 0.001]. The range of sHRs for GZF3SD mass (1–527) was wider than for TF2SD mass (1–37.6). Conclusions In CAD patients with an LVEF & gt;35%, GZF3SD mass was strongly associated with the arrhythmic endpoint. These findings hold promise for its use in identifying patients with CAD and an LVEF & gt;35% at risk of arrhythmic events.
    Type of Medium: Online Resource
    ISSN: 1099-5129 , 1532-2092
    URL: Article
    DOI: 10.1093/europace/euab167
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2002579-8
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  • 4
    Online Resource
    Online Resource
    Improved prognosis after cardiac resynchronization therapy over a decade
    Oxford University Press (OUP) ; 2023
    In:  Europace Vol. 25, No. 6 ( 2023-06-02)
    Details
    In: Europace, Oxford University Press (OUP), Vol. 25, No. 6 ( 2023-06-02)
    Abstract: The past decade has seen an increased delivery of cardiac resynchronization therapy (CRT) for patients with heart failure (HF). We explored whether clinical outcomes after CRT have changed from the perspective of an entire public healthcare system. Methods and results A national database covering the population of England (56.3 million in 2019) was used to explore clinical outcomes after CRT from 2010 to 2019. A total of 64 698 consecutive patients (age 71.4 ± 11.7 years; 74.8% male) underwent CRT-defibrillation [n = 32 313 (49.7%)] or CRT-pacing [n = 32 655 (50.3%)] implantation. From 2010–2011 to 2018–2019, there was a 76% increase in CRT implantations. During the same period, the proportion of patients with hypertension (59.6–73.4%), diabetes (26.5–30.8%), and chronic kidney disease (8.62–22.5%) increased, as did the Charlson comorbidity index (CCI ≥ 3 from 20.0% to 25.1%) (all P & lt; 0.001). Total mortality decreased at 30 days (1.43–1.09%) and 1 year (9.51–8.13%) after implantation (both P & lt; 0.001). At 2 years, total mortality [hazard ratio (HR): 0.72; 95% confidence interval (CI) 0.69–0.76] and total mortality or HF hospitalization (HR: 0.59; 95% CI 0.57–0.62) decreased from 2010–2011 to 2018–2019, after correction for age, race, sex, device type (CRT-defibrillation or pacing), comorbidities (hypertension, diabetes, chronic kidney disease, and myocardial infarction), or the CCI (HR: 0.81; 95% CI 0.77–0.85). Conclusions From the perspective of an entire public health system, survival has improved and HF hospitalizations have decreased after CRT implantation over the past decade. This prognostic improvement has occurred despite an increasing comorbidity burden.
    Type of Medium: Online Resource
    ISSN: 1099-5129 , 1532-2092
    URL: Article
    DOI: 10.1093/europace/euad141
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2002579-8
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  • 5
    Online Resource
    Online Resource
    Prognosis of incidental left bundle branch block
    Oxford University Press (OUP) ; 2020
    In:  EP Europace Vol. 22, No. 6 ( 2020-06-01), p. 956-963
    Details
    In: EP Europace, Oxford University Press (OUP), Vol. 22, No. 6 ( 2020-06-01), p. 956-963
    Abstract: Incidental left bundle branch block (iLBBB) is a frequent cause for cardiology referrals. In such instances, there is uncertainty as to its prognosis. We sought to determine the utility of cardiovascular magnetic resonance (CMR) in the risk stratification of patients with iLBBB. Methods and results Clinical events were collected in patients with iLBBB who had CMR. Controls had no cardiac symptoms or cardiac disease, a normal CMR scan and electrocardiogram. Amongst patients with iLBBB [n = 193, aged 62.7 ± 12.6 years (mean ± SD)], 110/193 (56.9%) had an abnormal phenotype (iLBBBCMR+) and 83/110 (43.0%) had a normal phenotype (iLBBBCMR−). Over 3.75 years (median; inter-quartile range: 2.7–5.5), iLBBBCMR+ had a higher total mortality [adjusted hazard ratio (aHR) 6.49, 95% confidence interval (CI) 1.91–22.0] and total mortality or major adverse cardiac events (MACEs; aHR 9.15, 95% CI 2.56–32.6) than controls (n = 107). In contrast, iLBBBCMR− had a similar risk of total mortality compared with controls, but total mortality or MACEs was higher (aHR 4.24, 95% CI 1.17–15.4; P = 0.028). Amongst iLBBB patients, both myocardial fibrosis (aHR 5.15, 95% CI 1.53–17.4) and left ventricular ejection fraction (LVEF)  ≤ 50% (aHR 3.88, 95% CI 1.67–9.06) predicted total mortality. Myocardial fibrosis plus LVEF ≤50% was associated with the highest risk of total mortality (aHR: 9.87, 95% CI 2.99–32.6) and total mortality or MACEs (aHR 3.98, 95% CI 1.73–9.11). Conclusions Outcomes in iLBBBCMR+ were poor whereas survival in iLBBBCMR− was comparable with controls. Myocardial fibrosis and LVEF & lt;50% had an additive effect on the risk of clinical outcomes. A CMR scan is pivotal in risk-stratifying patients with iLBBB.
    Type of Medium: Online Resource
    ISSN: 1099-5129 , 1532-2092
    URL: Article
    DOI: 10.1093/europace/euaa008
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 6
    Online Resource
    Online Resource
    Effects of haemodynamically atrio‐ventricular optimized His bundle pacing on heart failure symptoms and exercise capacity: the His Optimized Pacing Evaluated for Heart Failure ( HOPE‐HF ) randomized, double‐blind, cross‐over trial
    Wiley ; 2023
    In:  European Journal of Heart Failure Vol. 25, No. 2 ( 2023-02), p. 274-283
    Details
    In: European Journal of Heart Failure, Wiley, Vol. 25, No. 2 ( 2023-02), p. 274-283
    Abstract: Excessive prolongation of PR interval impairs coupling of atrio‐ventricular (AV) contraction, which reduces left ventricular pre‐load and stroke volume, and worsens symptoms. His bundle pacing allows AV delay shortening while maintaining normal ventricular activation. HOPE‐HF evaluated whether AV optimized His pacing is preferable to no‐pacing, in a double‐blind cross‐over fashion, in patients with heart failure, left ventricular ejection fraction (LVEF) ≤40%, PR interval ≥200 ms and either QRS ≤140 ms or right bundle branch block. Methods and results Patients had atrial and His bundle leads implanted (and an implantable cardioverter‐defibrillator lead if clinically indicated) and were randomized to 6 months of pacing and 6 months of no‐pacing utilizing a cross‐over design. The primary outcome was peak oxygen uptake during symptom‐limited exercise. Quality of life, LVEF and patients' holistic symptomatic preference between arms were secondary outcomes. Overall, 167 patients were randomized: 90% men, 69 ± 10 years, QRS duration 124 ± 26 ms, PR interval 249 ± 59 ms, LVEF 33 ± 9%. Neither peak oxygen uptake (+0.25 ml/kg/min, 95% confidence interval [CI] −0.23 to +0.73, p  = 0.3) nor LVEF (+0.5%, 95% CI −0.7 to 1.6, p  = 0.4) changed with pacing but Minnesota Living with Heart Failure quality of life improved significantly (−3.7, 95% CI −7.1 to −0.3, p  = 0.03). Seventy‐six percent of patients preferred His bundle pacing‐on and 24% pacing‐off ( p   〈  0.0001). Conclusion His bundle pacing did not increase peak oxygen uptake but, under double‐blind conditions, significantly improved quality of life and was symptomatically preferred by the clear majority of patients. Ventricular pacing delivered via the His bundle did not adversely impact ventricular function during the 6 months.
    Type of Medium: Online Resource
    ISSN: 1388-9842 , 1879-0844
    URL: Issue
    URL: Article
    DOI: 10.1002/ejhf.v25.2
    DOI: 10.1002/ejhf.2736
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 1500332-2
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  • 7
    Online Resource
    Online Resource
    Myocardial Fibrosis as a Predictor of Sudden Death in Patients With Coronary Artery Disease
    Elsevier BV ; 2021
    In:  Journal of the American College of Cardiology Vol. 77, No. 1 ( 2021-01), p. 29-41
    Details
    In: Journal of the American College of Cardiology, Elsevier BV, Vol. 77, No. 1 ( 2021-01), p. 29-41
    Type of Medium: Online Resource
    ISSN: 0735-1097
    URL: Article
    DOI: 10.1016/j.jacc.2020.10.046
    RVK:
    XA 17760
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 1468327-1
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  • 8
    Online Resource
    Online Resource
    Timing of cardiac resynchronization therapy implantation
    Oxford University Press (OUP) ; 2023
    In:  Europace Vol. 25, No. 5 ( 2023-05-19)
    Details
    In: Europace, Oxford University Press (OUP), Vol. 25, No. 5 ( 2023-05-19)
    Abstract: The optimum timing of cardiac resynchronization therapy (CRT) implantation is unknown. We explored long-term outcomes after CRT in relation to the time interval from a first heart failure hospitalization (HFH) to device implantation. Methods and results A database covering the population of England (56.3 million in 2019) was used to quantify clinical outcomes after CRT implantation in relation to first HFHs. From 2010 to 2019, 64 968 patients [age: 71.4 ± 11.7 years; 48 606 (74.8%) male] underwent CRT implantation, 57% in the absence of a previous HFH, 12.9% during the first HFH, and 30.1% after ≥1 HFH. Over 4.54 (2.80–6.71) years [median (interquartile range); 272 989 person-years] , the time in years from the first HFH to CRT implantation was associated with a higher risk of total mortality [hazard ratio (HR); 95% confidence intervals (95% CI)] (1.15; 95% CI 1.14–1.16, HFH (HR: 1.26; 95% CI 1.24–1.28), and the combined endpoint of total mortality or HFH (HR: 1.19; 95% CI 1.27–1.20) than CRT in patients with no previous HFHs, after co-variate adjustment. Total mortality (HR: 1.67), HFH (HR: 2.63), and total mortality or HFH (HR: 1.92) (all P & lt; 0.001) were highest in patients undergoing CRT ≥2 years after the first HFH. Conclusion In this study of a healthcare system covering an entire nation, delays from a first HFH to CRT implantation were associated with progressively worse long-term clinical outcomes. The best clinical outcomes were observed in patients with no previous HFH and in those undergoing CRT implantation during the first HFH. Condensed abstract The optimum timing of CRT implantation is unknown. In this study of 64 968 consecutive patients, delays from a first heart failure hospitalization (HFH) to CRT implantation were associated with progressively worse long-term clinical outcomes. Each year from a first HFH to CRT implantation was associated with a 21% higher risk of total mortality and a 34% higher risk of HFH. The best outcomes after CRT were observed in patients with no previous HFHs and in those undergoing implantation during their first HFH.
    Type of Medium: Online Resource
    ISSN: 1099-5129 , 1532-2092
    URL: Article
    DOI: 10.1093/europace/euad059
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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