Guideline adherence in the use of coronary angiography in patients presenting at the emergency department without myocardial infarction – results from the German ENLIGHT-KHK project

Background For patients with acute myocardial infarction (AMI), direct coronary angiography (CA) is recommended, while for non-AMI patients, the diagnostic work-up depends on clinical criteria. This analysis provides initial prospective German data for the degree of guideline-adherence (GL) in the use of CA on non-AMI patients presenting at the emergency department (ED) with suspected acute coronary syndrome (ACS) according to the 2015 ESC-ACS-GL. Furthermore the implications of the application of the 2020 ESC-ACS-GL recommendations were evaluated. Methods Patient symptoms were identified using a standardized questionnaire; medical history and diagnostic work-up were acquired from health records. In accordance with the 2015 ESC-ACS-GL, CA was considered GL-adherent if intermediate risk criteria (IRC) were present or non-invasive, image-guided testing (NIGT) was pathological. Results Between January 2019 and August 2021, 229 patients were recruited across seven centers. Patients presented with chest pain, dyspnea, and other symptoms in 66.7%, 16.2% and 17.1%, respectively, were in mean 66.3 ± 10.5 years old, and 36.3% were female. In accordance with the 2015 ESC-ACS-GL, the use of CA was GL-adherent for 64.0% of the patients. GL-adherent compared to non-adherent use of CA resulted in revascularization more often (44.5% vs. 17.1%, p < 0.001). Applying the 2020 ESC-ACS-GL, 20.4% of CA would remain GL-adherent. Conclusions In the majority of cases, the use of CA was adherent to the 2015 ESC-ACS-GL. With regard to the 2020 and 2023 ESC-ACS-GL, efforts to expand the utilization of NIGT are crucial, especially as GL-adherent use of CA is more likely to result in revascularization

Age-related differences in skeletal muscle microvascular response to exercise as detected by contrast-enhanced ultrasound (CEUS).

BACKGROUND:Aging involves reductions in exercise total limb blood flow and exercise capacity. We hypothesized that this may involve early age-related impairments of skeletal muscle microvascular responsiveness as previously reported for insulin but not for exercise stimuli in humans. METHODS:Using an isometric exercise model, we studied the effect of age on contrast-enhanced ultrasound (CEUS) parameters, i.e. microvascular blood volume (MBV), flow velocity (MFV) and blood flow (MBF) calculated from replenishment of Sonovue contrast-agent microbubbles after their destruction. CEUS was applied to the vastus lateralis (VLat) and intermedius (VInt) muscle in 15 middle-aged (MA, 43.6±1.5 years) and 11 young (YG, 24.1±0.6 years) healthy males before, during, and after 2 min of isometric knee extension at 15% of peak torque (PT). In addition, total leg blood flow as recorded by femoral artery Doppler-flow. Moreover, fiber-type-specific and overall capillarisation as well as fiber composition were additionally assessed in Vlat biopsies obtained from CEUS site. MA and YG had similar quadriceps muscle MRT-volume or PT and maximal oxygen uptake as well as a normal cardiovascular risk factors and intima-media-thickness. RESULTS:During isometric exercise MA compared to YG reached significantly lower levels in MFV (0.123±0.016 vs. 0.208±0.036 a.u.) and MBF (0.007±0.001 vs. 0.012±0.002 a.u.). In the VInt the (post-occlusive hyperemia) post-exercise peaks in MBV and MBF were significantly lower in MA vs. YG. Capillary density, capillary fiber contacts and femoral artery Doppler were similar between MA and YG. CONCLUSIONS:In the absence of significant age-related reductions in capillarisation, total leg blood flow or muscle mass, healthy middle-aged males reveal impaired skeletal muscle microcirculatory responses to isometric exercise. Whether this limits isometric muscle performance remains to be assessed

‘Total leg blood flow and conductance’.

<p>Mean (±SEM) total leg blood flow (femoral artery Duplex-Doppler flow), calculated total leg vascular conductance (leg blood flow per mean arterial pressure), and systolic as well as diastolic brachial arterial blood pressure at rest in middle-aged (MA, n = 15) compared to young (YG, n = 11) males after ~90 s of isometric exercise and ~60 s post-exercise. # for p<0.05 by unpaired Student’s t-test middle-aged MA vs. YG. * for p<0.05, ** for p<0.01, and *** for p<0.001 by paired Student’s t-test for changes relative to rest (baseline) within the group of MA or YG.</p

‘Means of measured replenishment curves and individual regression lines’.

<p>Fig 4a) Mean replenishment curves (RC) in the vastus lateralis (VLat; <i>upper panel</i>) and the vastus intemedius (VInt; <i>lower panel</i>) muscle ROI of middle-aged (MA, n = 15) compared to young (YG, n = 11) males during rest (left), after 70 s isometric exercise (middle), and 15 s post-exercise. Note differences in initial slope or in the plateau reached during or post-exercise. Fig 4b) Mean regression lines, corresponding to mean RC presented above in a) i.e. for the VLat (<i>upper panel</i>) and the VInt (<i>lower panel</i>) muscle ROI of middle-aged (MA, n = 15) compared to young (YG, n = 11) males during rest (left), after 70 s isometric exercise (middle), and 15 s post-exercise. Note the differences in initial slope or reached plateau during or post exercise. Furthermore, note that regression lines represent the mean of individual regression lines calculated for individual RCs (not the regression line calculated for mean RCs, presented above in a). For statistical differences between MA and YG regarding the RC-derived parameters of microvascular blood volume (MBV), flow velocity (MFV), and blood flow (MBF) please see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172771#pone.0172771.g005" target="_blank">Fig 5</a>.</p

‘Ultrasound and MRT imaging of CEUS and Biopsy muscle site’.

<p>Fig 2 a) US B-mode image of a typical combined vastus lateralis (VLat) and intermedius (VInt) CEUS scan with the scanner position chosen parallel to the VLat muscle fiber orientation (i.e. from proximal/lateral to distal/medial). The intramuscular septum separating both muscles is indicated, the mean depth was similar between middle aged (MA) and young (YG) subjects and not significantly different between the conditions before, during, and post-exercise (see also the ‘<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172771#sec006" target="_blank">Methods</a>‘ section on Contrast-enhances US (CEUS). d) Thigh MRT-imaging transversal section at the exact site of VLat muscle biopsy (<i>middle</i>) and CEUS recording as well as 1 cm proximal (<i>left</i>) and distal (<i>right</i>). Note that this MRT was obtained 3 h after a muscle biopsy to visualize the exact biopsy site (local fluid /blood accumulation) indicated by the arrow.</p

‘Time courses of the mean contrast-agent CEUS signals’.

<p>Time course of the mean (±SEM) Sonovue microbubble signal in the vastus lateralis (VLat; <i>upper panel</i>) and the vastus intermedius (VInt; <i>lower panel</i>) muscle region of interests (ROI) in middle-aged (MA, n = 15) and young (YG, n = 11) males in the experimental intervals: equilibration at rest (<i>left;</i> initial 180 s of Sonovue infusion), isometric exercise (<i>middle</i>; first 60 s of knee extension at 15% of PT), and post-exercise (<i>right;</i> initial 15 s after cessation of). Note the different time scales on the x-axis with these three conditions. The time intervals for repetitive Sonovue replenishment curve (RC) recording following high-MI US destruction of Sonovue microbubbles (See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172771#pone.0172771.g001" target="_blank">Fig 1</a>) are presented separately in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172771#pone.0172771.g004" target="_blank">Fig 4A</a> (mean RC curves) and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172771#pone.0172771.g004" target="_blank">Fig 4B</a> (means of the individual regression lines obtained from individual RC curves). * for p<0.05 MA vs YG by unpaired Student’s t-test.</p

‘Microvascular blood volume (MBV), flow velocity (MFV) and blood flow (MBF)’.

<p>Mean (±SEM) microvascular blood volume (MBV, <i>left</i>), flow velocity (MFV, <i>middle</i>), and blood flow (MBF, <i>right</i>) in the vastus lateralis (VLat; <i>upper panel</i>) and the vastus intemedius (VInt; <i>lower panel</i>) muscle ROI of middle-aged (MA, n = 15) compared to young (YG, n = 11) at rest (two measurements), after 70 and 95 s of isometric exercise and 15, 30 60 and 90 s post-exercise. Note that these data were individually calculated from individual RC curve regression before averaging them for MA or YG (for mean RCs and regression lines per group see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172771#pone.0172771.g004" target="_blank">Fig 4A</a>). # for p<0.05 by unpaired Student’s t-test middle-aged MA vs. YG. * for p<0.05, ** for p<0.01, and *** for p<0.001 by paired Student’s t-test for changes relative to rest (basline) within the group of MA or YG.</p

Anthropometry, cardiovascular risk factors as well as leg muscle mass, function and vascularisation.

<p>Anthropometry, cardiovascular risk factors as well as leg muscle mass, function and vascularisation.</p

‘Experimental protocol’.

<p>Fig 1a) Study protocol with time schedule for exercise, Sonovue infusion, CEUS recordings, as well as femoral artery Doppler and brachial blood pressure measurements at rest, during isometric exercise and during post-exercise hyperemia. The time points of high-MI US-destruction of the Sonovue microbubbles are indicated by arrows, each of which was followed by a low-MI recording of Sonovue replenishment curves covering 25 s. Fig 1b) Example of a torque recording during isometric knee extension as controlled by the subject through visual feed-back.</p

Histomorphometry of vastus lateralis muscle capillarisation and fiber composition.

<p>Histomorphometry of vastus lateralis muscle capillarisation and fiber composition.</p