Progress with Drug-Eluting Stent Technology from Early to New Generation Devices

__Abstract__ Percutaneous coronary interventions (PCI) are among the most frequently performed medical interventions worldwide refl

Offering ART refill through community health workers versus clinic-based follow-up after home-based same-day ART initiation in rural Lesotho: the VIBRA cluster-randomized clinical trial

BACKGROUND: Community-based antiretroviral therapy (ART) dispensing by lay workers is an important differentiated service delivery model in sub-Sahara Africa. However, patients new in care are generally excluded from such models. Home-based same-day ART initiation is becoming widespread practice, but linkage to the clinic is challenging. The pragmatic VIBRA (Village-Based Refill of ART) trial compared ART refill by existing lay village health workers (VHWs) versus clinic-based refill after home-based same-day ART initiation. METHODS AND FINDINGS: The VIBRA trial is a cluster-randomized open-label clinical superiority trial conducted in 249 rural villages in the catchment areas of 20 health facilities in 2 districts (Butha-Buthe and Mokhotlong) in Lesotho. In villages (clusters) randomized to the intervention arm, individuals found to be HIV-positive during a door-to-door HIV testing campaign were offered same-day ART initiation with the option of refill by VHWs. The trained VHWs dispensed drugs and scheduled clinic visits for viral load measurement at 6 and 12 months. In villages randomized to the control arm, participants were offered same-day ART initiation with clinic-based ART refill. The primary outcome was 12-month viral suppression. Secondary endpoints included linkage and 12-month engagement in care. Analyses were intention-to-treat. The trial was registered on ClinicalTrials.gov (NCT03630549). From 16 August 2018 until 28 May 2019, 118 individuals from 108 households in 57 clusters in the intervention arm, and 139 individuals from 130 households in 60 clusters in the control arm, were enrolled (150 [58%] female; median age 36 years [interquartile range 30-48]; 200 [78%] newly diagnosed). In the intervention arm, 48/118 (41%) opted for VHW refill. At 12 months, 46/118 (39%) participants in the intervention arm and 64/139 (46%) in the control arm achieved viral suppression (adjusted risk difference -0.07 [95% CI -0.20 to 0.06]; p = 0.256). Arms were similar in linkage (adjusted risk difference 0.03 [-0.10 to 0.16]; p = 0.630), but engagement in care was non-significantly lower in the intervention arm (adjusted risk difference -0.12 [-0.23 to 0.003]; p = 0.058). Seven and 0 deaths occurred in the intervention and control arm, respectively. Of the intervention participants who did not opt for drug refill from the VHW at enrollment, 41/70 (59%) mentioned trust or conflict issues as the primary reason. Study limitations include a rather small sample size, 9% missing viral load measurements in the primary endpoint window, the low uptake of the VHW refill option in the intervention arm, and substantial migration among the study population. CONCLUSIONS: The offer of village-based ART refill after same-day initiation led to similar outcomes as clinic-based refill. The intervention did not amplify the effect of home-based same-day ART initiation alone. The findings raise concerns about acceptance and safety of ART delivered by lay health workers after initiation in the community. TRIAL REGISTRATION: Registered with Clinicaltrials.gov (NCT03630549)

Health utility indexes in patients with acute coronary syndromes.

BACKGROUND: Acute coronary syndromes (ACS) have been associated with lower health utilities (HUs) compared with the general population. Given the prognostic improvements after ACS with the implementation of coronary angiography (eg, percutaneous coronary intervention (PCI)), contemporary HU values derived from patient-reported outcomes are needed. METHODS: We analysed data of 1882 patients with ACS 1 year after coronary angiography in a Swiss prospective cohort. We used the EuroQol five-dimensional questionnaire (EQ-5D) and visual analogue scale (VAS) to derive HU indexes. We estimated the effects of clinical factors on HU using a linear regression model and compared the observed HU with the average values of individuals of the same sex and age in the general population. RESULTS: Mean EQ-5D HU 1-year after coronary angiography for ACS was 0.82 (±0.16) and mean VAS was 0.77 (±0.18); 40.9% of participants exhibited the highest utility values. Compared with population controls, the mean EQ-5D HU was similar (expected mean 0.82, p=0.58) in patients with ACS, but the mean VAS was slightly lower (expected mean 0.79, p<0.001). Patients with ACS who are younger than 60 years had lower HU than the general population (<0.001). In patients with ACS, significant differences were found according to the gender, education and employment status, diabetes, obesity, heart failure, recurrent ischaemic or incident bleeding event and participation in cardiac rehabilitation (p<0.01). CONCLUSIONS: At 1 year, patients with ACS with coronary angiography had HU indexes similar to a control population. Subgroup analyses based on patients' characteristics and further disease-specific instruments could provide better sensitivity for detecting smaller variations in health-related quality of life

Design and fabrication of an integrated MEMS-based colloid micropropulsion system

The design, microfabrication and initial performance results of a prototype electrospray thruster with integrated individual extractor electrodes are reported in this paper. The aim was to demonstrate increased thrust with an array of emitters spraying simultaneously. Micromachining technologies were employed to achieve large emitter density per surface area, simple integration and good structural repeatability. The novelty of this work lies in the combination of high aspect ratio capillary emitters (height of 70 microns, inner diameter of 20 microns) with individual extractor electrodes having diameters from 80 microns upwards and a spacing as low as 25 microns from the capillary tips. The individual integrated electrodes, as opposed to the standard approach of one common electrode, allow for greater uniformity in critical voltages between capillaries and more finely modulated thrust control. Tests with the newly developed thrusters using the ionic liquid EMI-BF4 show that starting voltages below 700V and currents around 300nA per emitter can be achieved

Quality of care after acute coronary syndromes in a prospective cohort with reasons for non-prescription of recommended medications.

BACKGROUND: Adherence to guidelines is associated with improved outcomes of patients with acute coronary syndrome (ACS). Clinical registries developed to assess quality of care at discharge often do not collect the reasons for non-prescription for proven efficacious preventive medication in Continental Europe. In a prospective cohort of patients hospitalized for an ACS, we aimed at measuring the rate of recommended treatment at discharge, using pre-specified quality indicators recommended in cardiologic guidelines and including systematic collection of reasons for non-prescription for preventive medications. METHODS: In a prospective cohort with 1260 patients hospitalized for ACS, we measured the rate of recommended treatment at discharge in 4 academic centers in Switzerland. Performance measures for medication at discharge were pre-specified according to guidelines, systematically collected for all patients and included in a centralized database. RESULTS: Six hundred and eighty eight patients(54.6%) were discharged with a main diagnosis of STEMI, 491(39%) of NSTEMI and 81(6.4%) of unstable angina. Mean age was 64 years and 21.3% were women. 94.6% were prescribed angiotensin converting enzyme inhibitors/angiotensin II receptor blockers at discharge when only considering raw prescription rates, but increased to 99.5% when including reasons non-prescription. For statins, rates increased from 98% to 98.6% when including reasons for non-prescription and for beta-blockers, from 82% to 93%. For aspirin, rates further increased from 99.4% to 100% and from to 99.8% to 100% for P2Y12 inhibitors. CONCLUSIONS: We found a very high adherence to ACS guidelines for drug prescriptions at discharge when including reasons for non-prescription to drug therapy. For beta-blockers, prescription rates were suboptimal, even after taking into account reason for non-prescription. In an era of improving quality of care to achieve 100% prescription rates at discharge unless contra-indicated, pre-specification of reasons for non-prescription for cardiovascular preventive medication permits to identify remaining gaps in quality of care at discharge. TRIAL REGISTRATION: ClinicalTrials.gov NCT01000701

Diabetes and baseline glucose are associated with inflammation, left ventricular function and short- and long-term outcome in acute coronary syndromes: role of the novel biomarker Cyr 61.

Hyperglycemia in the setting of an acute coronary syndrome (ACS) impacts short term outcomes, but little is known about longer term effects. We therefore designed this study to firstly determine the association between hyperglycemia and short term and longer term outcomes in patients presenting with ACS and secondly evaluate the prognostic role of diabetes, body mass index (BMI) and the novel biomarker Cyr61 on outcomes. The prospective Special Program University Medicine-Acute Coronary Syndrome (SPUM-ACS) cohort enrolled 2168 patients with ACS between December 2009 and October 2012, of which 2034 underwent PCI (93.8%). Patients were followed up for 12 months. Events were independently adjudicated by three experienced cardiologists. Participants were recruited from four tertiary hospitals in Switzerland: Zurich, Geneva, Lausanne and Bern. Participants presenting with acute coronary syndromes and who underwent coronary angiography were included in the analysis. Patients were grouped according to history of diabetes (or HbA1c greater than 6%), baseline blood sugar level (BSL; < 6, 6-11.1 and > 11.1 mmol/L) and body mass index (BMI). The primary outcome was major adverse cardiac events (MACE) which was a composite of myocardial infarction, stroke and all-cause death. Secondary outcomes included the individual components of the primary endpoint, revascularisations, bleeding events (BARC classification) and cerebrovascular events (ischaemic or haemorrhagic stroke or TIA). Patients with hyperglycemia, i.e. BSL ≥ 11.1 mmol/L, had higher levels of C-reactive protein (CRP), white blood cell count (WBC), creatinine kinase (CK), higher heart rates and lower left ventricular ejection fraction (LVEF) and increased N-terminal pro-brain natriuretic peptide. At 30 days and 12 months, those with BSL ≥ 11.1 mmol/L had more MACE and death compared to those with BSL < 6.0 mmol/L or 6.0-11.1 mmol/L (HR-ratio 4.78 and 6.6; p < 0.001). The novel biomarker Cyr61 strongly associated with high BSL and STEMI and was independently associated with 1 year outcomes (HR 2.22; 95% CI 1.33-3.72; Tertile 3 vs. Tertile 1). In this large, prospective, independently adjudicated cohort of in all comers ACS patients undergoing PCI, both a history of diabetes and elevated entry glucose was associated with inflammation and increased risk of MACE both at short and long-term. The mediators might involve increased sympathetic activation, inflammation and ischemia as reflected by elevated Cyr61 levels leading to larger levels of troponin and lower LVEF. Trial registration Clinical Trial Registration Number: NCT01000701. Registered October 23, 2009

Five-year follow-up of underexpanded and overexpanded bioresorbable scaffolds: Self-correction and impact on shear stress

Underexpansion and overexpansion have been incriminated as causative factors of adverse cardiac events. However, dynamic biological interaction between vessel wall and scaffold may attenuate the adverse haemodynamic impact of overexpansion or underexpansion

Incidence, Predictors, and Clinical Impact of Early Prasugrel Cessation in Patients With ST-Elevation Myocardial Infarction.

BACKGROUND: Early withdrawal of recommended antiplatelet treatment with clopidogrel adversely affects prognosis following percutaneous coronary interventions. Optimal antiplatelet treatment is essential following ST-segment elevation myocardial infarction (STEMI) given the increased risk of thrombotic complications. This study assessed the frequency, predictors, and clinical impact of early prasugrel cessation in patients with STEMI undergoing primary percutaneous coronary interventions. METHODS AND RESULTS: We pooled patients with STEMI discharged on prasugrel in 2 prospective registries (Bern PCI Registry [NCT02241291] and SPUM-ACS (Inflammation and Acute Coronary Syndromes) [NCT01000701]) and 1 STEMI trial (COMFORTABLE-AMI (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction) [NCT00962416]). Prasugrel treatment status at 1 year was categorized as no cessation; crossover to another P2Y12-inhibitor; physician-recommended discontinuation; and disruption because of bleeding, side effects, or patient noncompliance. In time-dependent analyses, we assessed the impact of prasugrel cessation on the primary end point, a composite of cardiac death, myocardial infarction, and stroke. Of all 1830 included patients (17% women, mean age 59 years), 83% were treated with new-generation drug-eluting stents. At 1 year, any prasugrel cessation had occurred in 13.8% of patients including crossover (7.2%), discontinuation (3.7%), and disruption (2.9%). Independent predictors of any prasugrel cessation included female sex, age, and history of cerebrovascular event. The primary end point occurred in 5.2% of patients and was more frequent following disruption (hazard ratio 3.04, 95% confidence interval,1.34-6.91; P=0.008), without significant impact of crossover or discontinuation. Consistent findings were observed for all-cause death, myocardial infarction, and stent thrombosis following prasugrel disruption. CONCLUSIONS: In this contemporary study of patients with STEMI, early prasugrel cessation was not uncommon and primarily involved change to another P2Y12-inhibitor. Disruption was the only type of early prasugrel cessation associated with statistically significant excess in ischemic risk within 1 year following primary percutaneous coronary interventions

Quantitative Flow Ratio to Predict Nontarget Vessel-Related Events at 5 Years in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Angiography-Guided Revascularization.

Background In ST-segment-elevation myocardial infarction, angiography-based complete revascularization is superior to culprit-lesion-only percutaneous coronary intervention. Quantitative flow ratio (QFR) is a novel, noninvasive, vasodilator-free method used to assess the hemodynamic significance of coronary stenoses. We aimed to investigate the incremental value of QFR over angiography in nonculprit lesions in patients with ST-segment-elevation myocardial infarction undergoing angiography-guided complete revascularization. Methods and Results This was a retrospective post hoc QFR analysis of untreated nontarget vessels (any degree of diameter stenosis [DS]) from the randomized multicenter COMFORTABLE AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) trial by assessors blinded for clinical outcomes. The primary end point was cardiac death, spontaneous nontarget vessel myocardial infarction, and clinically indicated nontarget vessel revascularization (ie, ≥70% DS by 2-dimensional quantitative coronary angiography or ≥50% DS and ischemia) at 5 years. Of 1161 patients with ST-segment-elevation myocardial infarction, 946 vessels in 617 patients were analyzable by QFR. At 5 years, the rate of the primary end point was significantly higher in patients with QFR ≤0.80 (n=35 patients, n=36 vessels) versus QFR >0.80 (n=582 patients, n=910 vessels) (62.9% versus 12.5%, respectively; hazard ratio [HR], 7.33 [95% CI, 4.54-11.83], P30% DS by 3-dimensional quantitative coronary angiography. Conclusions Our study suggests incremental value of QFR over angiography-guided percutaneous coronary intervention for nonculprit lesions among patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention