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Morphine reduces absorption and delays action onset of potent oral P2Y₁₂ receptor inhibitors in patients with ST-segment elevation myocardial infarction (STEMI). We sought to determine the differential effects of fentanyl compared to morphine on the pharmacodynamics and pharmacokinetics of ticagrelor in STEMI patients undergoing primary percutaneous coronary intervention (PCI).PERSEUS (NCT02531165) was a prospective, single-center, open-label, randomized controlled study. Patients with STEMI who required analgesia were randomly assigned in a 1:1 ratio to treatment with intravenous fentanyl or morphine after ticagrelor loading dose (LD) administration. The primary endpoint was platelet reactivity at 2 hours after ticagrelor LD assessed by P2Y₁₂ reaction units (PRU).The study was prematurely stopped in June 2017 after enrolment of 38 out of 56 planned patients. PRU at 2 hours following ticagrelor LD was 173.3 ± 89.7 in the fentanyl group and 210.3 ± 76.4 in the morphine group (p = 0.179). At 4 hours, PRU was significantly lower among patients treated with fentanyl as compared to those treated with morphine (90.1 ± 97.4 vs. 168.0 ± 72.2; p = 0.011). Maximal plasma concentrations of ticagrelor and its active metabolite AR-C124910XX tended to be delayed and numerically lower among patients treated with morphine compared to fentanyl. Total exposures to ticagrelor and AR-C124910XX within 6 hours after ticagrelor LD were numerically greater among patients treated with fentanyl compared to those treated with morphine.In patients with STEMI undergoing primary PCI, fentanyl did not improve platelet inhibition at 2 hours after ticagrelor pre-treatment compared with morphine. Fentanyl may, however, accelerate ticagrelor absorption and increase platelet inhibition at 4 hours compared to morphine.

Compared with the general population, oncology patients face a higher morbidity and mortality caused by the COVID-19 pandemic. As a result, health systems had to quickly adapt cancer care in order to maintain the best quality and patient safety. From March to May and from October to December 2020, 254 patients diagnosed with cancer and tested positive for SARS-CoV-2 benefited from a tele-health monitoring at the Oncology Department at CHUV. This article describes the key points of the development, implementation and operation of this tele-health monitoring, enabled by an interdisciplinary and inter-professional collaboration between different units and healthcare professionals.En comparaison de la population générale, les patients oncologiques font face à une augmentation de leur morbimortalité en lien avec la pandémie de Covid-19. Par conséquent, les systèmes de santé ont dû s’adapter rapidement dans ce contexte instable afin de poursuivre des soins de qualité tout en assurant la sécurité des patients. De mars à mai ainsi que d’octobre à décembre 2020, un total de 254 patients oncologiques testés positifs au SARS-CoV-2 ont bénéficié d’un suivi téléphonique au Département d’oncologie du CHUV. Cet article décrit les points clés de l’implantation et du fonctionnement de ce télésuivi, grâce à la collaboration entre différentes unités et une équipe interprofessionnelle.

BACKGROUND: The occurrence of congestive heart failure (CHF) hospitalization among patients with atrial fibrillation (AF) is a poor prognostic marker. OBJECTIVE: The purpose of this study was to assess whether insulin-like growth factor-binding protein 7 (IGFBP-7), a marker of myocardial damage, identifies AF patients at high risk for this complication. METHODS: We analyzed 2 prospective multicenter observational cohort studies that included 3691 AF patients. Levels of IGFBP-7 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured from frozen plasma samples at baseline. The primary endpoint was hospitalization for CHF. Multivariable adjusted Cox regression analyses were constructed. RESULTS: Mean patient age was 69 ± 12 years, 1028 (28%) were female, and 879 (24%) had a history of CHF. The incidence per 1000 patient-years across increasing IGFBP-7 quartiles was 7, 10, 32, and 85. The corresponding multivariable adjusted hazard ratios (aHRs) (95% confidence interval [CI]) were 1.0, 1.05 (0.63-1.77), 2.38 (1.50-3.79), and 4.37 (2.72-7.04) (P for trend

The circadian variation of platelet aggregation is well demonstrated. However, whether this has an impact on antiplatelet inhibition therapy is poorly documented. We aimed to observe whether ticagrelor-induced platelet inhibition follows a circadian rhythm. The study included 25 healthy volunteers (11 female; 14 male). Blood samples were collected every 4 h. Ticagrelor was added in vitro at a concentration that provided 50% inhibition of the maximum response using the VerifyNow System Platelet Reactivity Test® thus avoiding any bias induced by circadian gastrointestinal absorption. Platelet aggregation testing was subsequently performed using the VerifyNow. Circadian changes in total platelet count, percentage of platelets inhibition, Von Willebrand activity, and volunteers' physiological parameters were analysed by fitting individuals' data to a sine curve with a 24-h period. Volunteers' physiological parameters [heart rate (b.p.m.), systolic/diastolic blood pressure (mmHg), and body temperature (Celsius)] followed a significant mean circadian pattern of 6 b.p.m. (P

High-sensitivity cardiac troponin assays have significantly improved the sensitivity of myocardial infarction detection by using cutoff values and early absolute changes. However, variation in repeated measures also depends on biological variability. This study aimed to assess the potential circadian component of this biological variability. 17 healthy volunteers were recruited, and standardized conditions for physical activity, meals, exposure to light and duration of sleep were imposed. Blood samples were collected every 4 h and high-sensitivity troponin T assay with a limit of detection of 3 ng/l and a 99th percentile of 14 ng/l were used. Circadian variations were analyzed using the cosinor method. Statistically significant circadian variations were observed for body temperature, heart rate, and systolic/diastolic arterial blood pressures (p

In search of a non-invasive alternative detection of early-stage cardiac allograft vasculopathy (CAV), in this preliminary study we tested the hypothesis that interstitial fibrosis quantified with cardiac magnetic resonance (CMR) can serve as a biomarker for the detection of CAV. Late-stage CAV was detected with routine X-ray coronary angiography (XRCA), while a coronary intima-media thickness ratio (IMTR) > 1 on optical coherence tomography (OCT) was used to detect early-stage CAV. Interstitial fibrosis was quantified in the endomyocardial biopsy (EMB) and indirectly with CMR as the T 1 relaxation time and extracellular volume (ECV). CMR was performed within 48 h of a single invasive procedure with XRCA, OCT, and EMB procurement in stable HTx recipients (n = 27; age 54 ± 13 years, 5.4 ± 3.7 years post-transplant). XRCA-CAV and IMTR > 1 were present in 15% and 75% of study patients, respectively. The T 1 relaxation times and ECV were increased in patients with XRCA-CAV (p = 0.03 each), while IMTR and EMB interstitial fibrosis were not significantly different (both p > 0.05). ECV (ρ = 0.46, p = 0.02) and IMTR (ρ = 0.58; p = 0.01) correlated with the histological quantity of interstitial fibrosis, while the T 1 relaxation time (p = 0.06) did not. The correlation of the IMTR with the EMB interstitial fibrosis tentatively validates the hypothesis that interstitial fibrosis may serve as an early indicator of CAV. Moreover, the significant association of CMR-based ECV with the magnitude of interstitial fibrosis in the biopsy suggests ECV as a potential biomarker for interstitial fibrosis due to early-stage CAV. The measurement of ECV may therefore have a role for non-invasive detection and follow-up of early-stage CAV.

The present study aimed to document a local pattern of care in consecutive patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI) in a tertiary centre in Switzerland.A retrospective study was conducted at the University Hospital of Lausanne, Switzerland. A total of 389 consecutive patients undergoing primary percutaneous coronary intervention for STEMI between 2009 and 2010 were studied. The audit focused on 14 items derived from the American College of Cardiology/American Heart Association 2008 quality performance measures position paper on STEMI management. These indicators all corresponded to a class 1 recommendation at the time of the study period.All patients received aspirin and anticoagulation within 24 hours after admission. Only 31.3% of patients received beta-blocking agents within 24 hours of admission. Left ventricular function was evaluated in 89.2% of cases and referral for cardiac rehabilitation was achieved in 78.5% of eligible patients. Patients subsequently transferred to another facility for further inpatient care had significantly less evaluation of left ventricular function (82.0% vs. 97.5%, P0.0001). Global adherence to all performance measures was significantly higher among younger patients (45.9% vs. 31.4%, P0.0075).The present study, which provides a snapshot on quality performance between 2009 and 2010 in a referral centre for primary percutaneous coronary intervention, demonstrates a suboptimal application of the global guidelines on STEMI management. This observation is mainly driven by a low prescription of beta-blocking agents, a class IA indication at that time. This observation should be put in perspective to current practice.

BACKGROUND Patients with atrial fibrillation (AF) have an increased risk of cognitive decline, potentially resulting from clinically unrecognized vascular brain lesions. OBJECTIVES This study sought to assess the relationships between cognitive function and vascular brain lesions in patients with AF. METHODS Patients with known AF were enrolled in a multicenter study in Switzerland. Brain magnetic resonance imaging (MRI) and cognitive testing using the Montreal Cognitive Assessment (MoCA) were performed in all participants. Large noncortical or cortical infarcts (LNCCIs), small noncortical infarcts (SNCIs), microbleeds, and white matter lesions were quantified by a central core laboratory. Clinically silent infarcts were defined as infarcts on brain MRI in patients without a clinical history of stroke or transient ischemic attack. RESULTS The study included 1,737 patients with a mean age of 73 ± 8 years (28% women, 90% taking oral anticoagulant agents). On MRI, LNCCIs were found in 387 patients (22%), SNCIs in 368 (21%), microbleeds in 372 (22%), and white matter lesions in 1715 (99%). Clinically silent infarcts among the 1,390 patients without a history of stroke or transient ischemic attack were found in 201 patients with LNCCIs (15%) and 245 patients with SNCIs (18%). The MoCA score was 24.7 ± 3.3 in patients with and 25.8 ± 2.9 in those without LNCCIs on brain MRI (p < 0.001). The difference in MoCA score remained similar when only clinically silent LNCCIs were considered (24.9 ± 3.1 vs. 25.8 ± 2.9; p < 0.001). In a multivariable regression model including all vascular brain lesion parameters, LNCCI volume was the strongest predictor of a reduced MoCA (β = -0.26; 95% confidence interval: -0.40 to -0.13; p < 0.001). CONCLUSIONS Patients with AF have a high burden of LNCCIs and other brain lesions on systematic brain MRI screening, and most of these lesions are clinically silent. LNCCIs were associated with worse cognitive function, even among patients with clinically silent infarcts. Our findings raise the question of MRI screening in patients with AF.

Aims Recent evidence demonstrates that intravenous morphine significantly reduces absorption and delays onset of action of oral P2Y12 receptor inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). We aimed to assess the influence of intravenous fentanyl compared with morphine on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) in patients undergoing pPCI for STEMI. Methods and results Single-centre, prospective, open-label, randomized controlled study that will randomly assign in a 1:1 ratio patients with STEMI undergoing pPCI to receive intravenous fentanyl or morphine following a pre-hospital 180-mg loading dose of ticagrelor (ClinicalTrials.gov Identifier: NCT02531165). Pharmacokinetic and pharmacodynamic analyses will be performed at baseline and 1, 2, 4, 6, and 12 h post-loading dose. Pharmacodynamic assessments will include P2Y12 reaction units (PRU) measured by VerifyNow P2Y12. Pharmacokinetic assessments include determination of maximal observed plasma concentrations, time for maximal plasma concentration, and area under the plasma concentration vs. time curve from time 0 to the last measurable concentration (AUC0-t) for ticagrelor and AR-C124910XX. The primary endpoint is platelet reactivity assessed by PRU at 2 h post ticagrelor loading dose. Conclusion PERSEUS will provide randomized data regarding the impact of fentanyl administration, in patients with STEMI undergoing pPCI, on platelet inhibition and ticagrelor absorption and total exposure.

ObjectivesThis study sought to establish an accurate and reproducible T2-mapping cardiac magnetic resonance (CMR) methodology at 3 T and to evaluate it in healthy volunteers and patients with myocardial infarct.BackgroundMyocardial edema affects the T2 relaxation time on CMR. Therefore, T2-mapping has been established to characterize edema at 1.5 T. A 3 T implementation designed for longitudinal studies and aimed at guiding and monitoring therapy remains to be implemented, thoroughly characterized, and evaluated in vivo.MethodsA free-breathing navigator-gated radial CMR pulse sequence with an adiabatic T2 preparation module and an empirical fitting equation for T2 quantification was optimized using numerical simulations and was validated at 3 T in a phantom study. Its reproducibility for myocardial T2 quantification was then ascertained in healthy volunteers and improved using an external reference phantom with known T2. In a small cohort of patients with established myocardial infarction, the local T2 value and extent of the edematous region were determined and compared with conventional T2-weighted CMR and x-ray coronary angiography, where available.ResultsThe numerical simulations and phantom study demonstrated that the empirical fitting equation is significantly more accurate for T2 quantification than that for the more conventional exponential decay. The volunteer study consistently demonstrated a reproducibility error as low as 2 ± 1% using the external reference phantom and an average myocardial T2 of 38.5 ± 4.5 ms. Intraobserver and interobserver variability in the volunteers were –0.04 ± 0.89 ms (p = 0.86) and –0.23 ± 0.91 ms (p = 0.87), respectively. In the infarction patients, the T2 in edema was 62.4 ± 9.2 ms and was consistent with the x-ray angiographic findings. Simultaneously, the extent of the edematous region by T2-mapping correlated well with that from the T2-weighted images (r = 0.91).ConclusionsThe new, well-characterized 3 T methodology enables robust and accurate cardiac T2-mapping at 3 T with high spatial resolution, while the addition of a reference phantom improves reproducibility. This technique may be well suited for longitudinal studies in patients with suspected or established heart disease.

Background: Several parameters of cardiovascular physiology and pathophysiology exhibit circadian rhythms. Recently, a relation between infarct size and the time of day at which it occurs has been suggested in experimental models of myocardial infarction. The aim of this study is to investigate whether circadian rhythms could cause differences in ischemic burden in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI).Methods: In 353 consecutive patients with STEMI treated by PPCI, time of symptom onset, peak creatine kinase (CK), and follow-up at 30 days were obtained. We divided 24 hours into 4 time groups based on time of symptom onset (00:00-05:59, 06:00-11:59, 12:00-17:59, and 18:00-23:59).Results: There was no difference between the groups regarding baseline patients and management's characteristics. At multivariable analysis, there was a statistically significant difference between peak CK levels among patients with symptom onset between 00:00 and 05:59 when compared with peak CK levels of patients with symptom onset in any other time group (mean increase 38.4%, P < .05). Thirty-day mortality for STEMI patients with symptom onset occurring between 00:00 and 05:59 was significantly higher than any other time group (P < .05).Conclusion: This study demonstrates an independent correlation between the infarct size of STEMI patients treated by PPCI and the time of the day at which symptoms occurred. These results suggest that time of the day should be a critical issue to look at when assessing prognosis of patients with myocardial infarction.

Background Highly sensitive troponin T (hs-TnT) assay has improved clinical decision-making for patients admitted with chest pain. However, this assay’s performance in detecting myocardial ischaemia in a lowrisk population has been poorly documented. Purpose To assess hs-TnT assay’s performance to detect myocardial ischaemia at positron emission tomography/CT (PET-CT) in low-risk patients admitted with chest pain. Methods Patients admitted for chest pain with a nonconclusive ECG and negative standard cardiac troponin T results at admission and after 6 hours were prospectively enrolled. Their hs-TnT samples were at T0, T2 and T6. Physicians were blinded to hs-TnT results. All patients underwent a PET-CT at rest and during adenosine-induced stress. All patients with a positive PET-CT result underwent a coronary angiography. Results Forty-eight patients were included. Six had ischaemia at PET-CT. All of them had ≥1 significant stenosis at coronary angiography. Areas under the curve (95% CI) for predicting significant ischaemia at PET-CT using hs-TnT were 0.764 (0.515 to 1.000) at T0, 0.812(0.616 to 1.000) at T2 and 0.813(0.638 to 0.989) at T6. The receiver operating characteristicbased optimal cut-off value for hs-TnT at T0, T2 and T6 needed to exclude significant ischaemia at PET-CT was

Background Cardiovascular magnetic resonance (CMR) has become an important diagnostic imaging modality in cardiovascular medicine. However, insufficient image quality may compromise its diagnostic accuracy. We aimed to describe and validate standardized criteria to evaluate a) cine steady-state free precession (SSFP), b) late gadolinium enhancement (LGE), and c) stress first-pass perfusion images. These criteria will serve for quality assessment in the setting of the Euro-CMR registry. Methods Thirty-five qualitative criteria were defined (scores 0–3) with lower scores indicating better image quality. In addition, quantitative parameters were measured yielding 2 additional quality criteria, i.e. signal-to-noise ratio (SNR) of non-infarcted myocardium (as a measure of correct signal nulling of healthy myocardium) for LGE and % signal increase during contrast medium first-pass for perfusion images. These qualitative and quantitative criteria were assessed in a total of 90 patients (60 patients scanned at our own institution at 1.5T (n=30) and 3T (n=30) and in 30 patients randomly chosen from the Euro-CMR registry examined at 1.5T). Analyses were performed by 2 SCMR level-3 experts, 1 trained study nurse, and 1 trained medical student. Results The global quality score was 6.7±4.6 (n=90, mean of 4 observers, maximum possible score 64), range 6.4-6.9 (p=0.76 between observers). It ranged from 4.0-4.3 for 1.5T (p=0.96 between observers), from 5.9-6.9 for 3T (p=0.33 between observers), and from 8.6-10.3 for the Euro-CMR cases (p=0.40 between observers). The inter- (n=4) and intra-observer (n=2) agreement for the global quality score, i.e. the percentage of assignments to the same quality tertile ranged from 80% to 88% and from 90% to 98%, respectively. The agreement for the quantitative assessment for LGE images (scores 0–2 for SNR 5, respectively) ranged from 78-84% for the entire population, and 70-93% at 1.5T, 64-88% at 3T, and 72-90% for the Euro-CMR cases. The agreement for perfusion images (scores 0–2 for %SI increase >200%, 100%-200%, Conclusions The described criteria for the assessment of CMR image quality are robust with a good inter- and intra-observer agreement. Further research is needed to define the impact of image quality on the diagnostic and prognostic yield of CMR studies.

Background Recently, T2-weighted MRI for the characterization of edema after myocardial infarction has attracted considerable attention (Friedrich, NatRevCardiol2010). Furthermore, the recently proposed combination of bSSFP imaging and T2Prep for T2-mapping at 1.5T has enabled a rapid quantitative cardiac T2 estimation (Huang et al., MRM2007). However, the accuracy of this method may still be limited due to the complex T2/T1 signal weighting. Especially for longitudinal studies designed for monitoring and/or guiding therapy, accurate and reproducible T2 measurements will be critical. A novel quantitative 3T T2-mapping protocol was therefore developed and tested in both healthy volunteers and patients.