Clinical decision making in frequently encountered anomalous aortic origin of coronary arteries, the impact of IVUS

Introduction The aim in the diagnostic work-up of patients with an anomalous aortic origin of coronary arteries (AAOCA) is to determine whether the course of the coronary artery is benign or malignant. In patients with AAOCA with an interarterial course the guidelines on diagnostics are concise. Recommended CT-scan imaging does not evaluate stress-induced functional consequences like external compression by the pulmonary artery as the scan is performed in a resting state. Non-invasive ischemia detection techniques often lack sufficient sensitivity. To improve functional stratification, exploration of new diagnostic modalities in the diagnostic workup of AAOCA is mandatory. Purpose The purpose is to explore the potential role of intravascular ultrasound (IVUS) in the diagnostic workup of patients with AAOCA. Methods Nine patients with an anomalous right coronary artery with an interarterial course were analyzed. A cardiologist evaluated the complaints. Anatomical features of the AAOCA were assessed with CT-scan imaging. Further analyses included ischemia detection and coronary angiography. To assess stress-induced ischemia IVUS and invasive measurements – fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) – were performed at rest and during adrenaline-induced stress. A slit-like orifice was classified as a width/length (W/L) ratio of ≤0.50, an oval orifice as 0.51–0.9 and a round orifice as >0.91. Results Potential cardiac complaints were present in seven patients. In 8 (89%) patients CT-images showed an acute angle, in 8 (89%) proximal narrowing and an aortic take-off above the pulmonary valve in 4 (44%). In 7 (78%) patients a slit-like orifice and in two (22%) an oval orifice were observed (table 1). IVUS at rest showed a slit-like orifice in one patient classified as an oval orifice on the CT-images and vice versa in another patient (table 2). The patients classified as an oval orifice with IVUS showed no external compression during adrenaline-induced stress. In 4 (57%) out of 7 patients with an slit-like orifice on IVUS, the width remained unchanged or increased during adrenaline infusion. In 2 patients the width decreased slightly, however, these patients were asymptomatic and no ischemia was detected. In 1 (14%) patient the width remained 1.4mmm and the length increased from 3.2mm to 4.7mm. In this case the vessel ostium was fully engaged with the IVUS catheter, hence, the width could not decrease during adrenaline infusion. This was regarded as external compression. In addition, in this patient ischemia was detected. Conclusion(s) In two (22%) out of 9 patients IVUS gave a better insight of the shape of the orifice than CT. Additionally, the anatomic and functional-dynamic components of compression could be defined with adrenaline-induced stress. Therefore, IVUS can contribute to a better understanding of the functional consequences of the anatomical features and of potential stress-induced external compression. FUNDunding Acknowledgement Type of funding sources: None. Table 1 Table 2

The effects of moderate alterations in adrenergic activity on acute appetite regulation in obese women: A randomised crossover trial

Background: Previous evidence has demonstrated that serum leptin is correlated with appetite in combination with, but not without, modest exercise. Aim: The present experiments investigated the effects of exogenous adrenaline and α/β adrenoceptor blockade in combination with moderate exercise on serum leptin concentrations, appetite/satiety sensations and subsequent food intake in obese women. Methods: A total of 10 obese women ((mean ± SEM), age: 50 (1.9) years, body mass index 36 (4.1) kg/m2, waist 104.8 (4.1) cm) participated in two separate, double-blind randomised experimental trials. Experiment 1: moderate exercise after α/β adrenergic blocker (labetalol, 100 mg orally) versus moderate exercise plus placebo; experiment 2: adrenaline infusion for 20 minutes versus saline infusion. Appetite/satiety and biochemistry were measured at baseline, pre- and immediately post-intervention, then 1 hour post-intervention (i.e., before dinner). Food intake was assessed via ad libitum buffet-style dinner. Results: No differences were found in appetite/satiety, subsequent food intake or serum leptin in any of the studies (experiment 1 or experiment 2). In experiment 1, blood glucose was higher ( p < 0.01) and plasma free fatty acids lower ( p = 0.04) versus placebo. In experiment 2, plasma free fatty acids ( p < 0.05) increased after adrenaline versus saline infusion. Conclusions: Neither inhibition of exercise-induced adrenergic activity by combined α/β adrenergic blockade nor moderate increases in adrenergic activity induced by intravenous adrenaline infusion affected acute appetite regulation.

Acute Severe Anaphylaxis in Nepali Patients with Neurotoxic Snakebite Envenoming Treated with the VINS Polyvalent Antivenom

Diagnosing and treating acute severe and recurrent antivenom-related anaphylaxis (ARA) is challenging and reported experience is limited. Herein, we describe our experience of severe ARA in patients with neurotoxic snakebite envenoming in Nepal. Patients were enrolled in a randomised, double-blind trial of high vs. low dose antivenom, given by intravenous (IV) push, followed by infusion. Training in ARA management emphasised stopping antivenom and giving intramuscular (IM) adrenaline, IV hydrocortisone, and IV chlorphenamine at the first sign/s of ARA. Later, IV adrenaline infusion (IVAI) was introduced for patients with antecedent ARA requiring additional antivenom infusions. Preantivenom subcutaneous adrenaline (SCAd) was introduced in the second study year (2012). Of 155 envenomed patients who received ≥ 1 antivenom dose, 13 (8.4%), three children (aged 5−11 years) and 10 adults (18−52 years), developed clinical features consistent with severe ARA, including six with overlapping signs of severe envenoming. Four and nine patients received low and high dose antivenom, respectively, and six had received SCAd. Principal signs of severe ARA were dyspnoea alone (n=5 patients), dyspnoea with wheezing (n=3), hypotension (n=3), shock (n=3), restlessness (n=3), respiratory/cardiorespiratory arrest (n=7), and early (n=1) and late laryngeal oedema (n=1); rash was associated with severe ARA in 10 patients. Four patients were given IVAI. Of the 8 (5.1%) deaths, three occurred in transit to hospital. Severe ARA was common and recurrent and had overlapping signs with severe neurotoxic envenoming. Optimising the management of ARA at different healthy system levels needs more research. This trial is registered withNCT01284855.

Adrenaline Improves Platelet Reactivity in Ticagrelor-Treated Healthy Volunteers

Background Administration of agents that enhance platelet reactivity may reduce the perioperative bleeding risk in patients treated with the adenosine diphosphate (ADP)-receptor antagonist ticagrelor. Adrenaline potentiates ADP-induced aggregation and activation in blood samples from ticagrelor-treated patients, but it has not previously been evaluated in vivo. Methods Ten healthy male subjects were included in an interventional study. A loading dose of ticagrelor (180 mg) was administered, followed 2 hours later by a gradually increased intravenous adrenaline infusion (0.01, 0.05, 0.10 and 0.15 µg/kg/min; 15 minutes at each step). Blood pressure, heart rate, platelet aggregation (impedance aggregometry), platelet activation (flow cytometry), clot formation (rotational thromboelastometry) and adrenaline plasma concentration were determined before and after ticagrelor administration and at the end of each adrenaline step. Results Infusion of adrenaline increased ADP-induced aggregation at all doses above 0.01 µg/kg/min. The aggregation increased from median 17 (25−75th percentiles: 14−31) to 25 (21−34) aggregation units (p = 0.012) at 0.10 µg/kg/min. Adrenaline infusion also increased ADP-induced fibrinogen receptor activation (from 29 [22–35] to 46 [38−57%]) and P-selectin expression (from 3.7 [3.0−4.3] to 7.7 [4.7−8.6%]), both p = 0.012. Adrenaline infusion reduced clot formation time (97 [89−110] to 83 [76−90] seconds, p = 0.008) and increased maximum clot firmness (59 [57−60] to 62 [61−64] mm, p = 0.007). Conclusion Infusion of adrenaline at clinically relevant doses improves in vivo platelet reactivity and clot formation in ticagrelor-treated subjects. Adrenaline could thus potentially be used to prevent perioperative bleeding complications in ticagrelor-treated patients. Studies in patients are necessary to determine the clinical importance of our observations. Trial Registry Number ClinicalTrials.gov NCT03441412.

Epinephrine (Adrenaline) Preventing Recovery from Intraoperative Anaphylactic Shock Complicated by Systolic Anterior Motion of the Mitral Valve with Left Ventricular Outflow Tract Obstruction on Transoesophageal Echocardiography

We describe a case of severe left ventricular outflow tract obstruction (LVOTO) with severe mitral incompetence due to systolic anterior motion of the anterior mitral leaflet (SAM) that was recognised thanks to the immediate availability of transoesophageal echocardiography during the resuscitation of anaphylactic shock. The patient rapidly responded to cessation of the epinephrine (adrenaline) infusion and intravascular volume expansion with intravenous crystalloid. The absence of risk factors for developing SAM/LVOTO serve as a warning to clinicians to consider this diagnosis in all cases of epinephrine non-responsive anaphylactic shock.