Angioedema Related to Angiotensin-Converting Enzyme Inhibitors: Attack Severity,Treatment, and Hospital Admission in a Prospective Multicenter Study

The number of cases of acquired angioedema related to angiotensin converting enzyme inhibitors induced (ACEI-AAE) is on the increase, with a potential concomitant increase in life-threatening attacks of laryngeal edema. Our objective was to determine the main characteristics of ACEI-AAE attacks and, in doing so, the factors associated with likelihood of hospital admission from the emergency department (ED) after a visit for an attack.A prospective, multicenter, observational study (April 2012–December 2014) was conducted in EDs of 4 French hospitals in collaboration with emergency services (SAMU 93) and a reference center for bradykinin-mediated angioedema. For each patient presenting with an attack, emergency physicians collected demographic and clinical presentation data, treatments, and clinical course. They recorded time intervals from symptom onset to ED arrival and to treatment decision, from ED arrival to specific treatment with plasma-derived C1-inhibitor (C1-INH) or icatibant, and from specific treatment to onset of symptom relief. Attacks requiring hospital admission were compared with those not requiring admission.Sixty-two eligible patients with ACEI-AAE (56% men, median age 63 years) were included. Symptom relief occurred significantly earlier in patients receiving specific treatment than in untreated patients (0.5 [0.5–1.0] versus 3.9 [2.5–7.0] hours; P < 0.0001). Even though icatibant was injected more promptly than plasma-derived C1-INH, there, however, was no significant difference in median time to onset of symptom relief between the 2 drugs (0.5 [0.5–1.3] versus 0.5 [0.4–1.0] hours for C1-INH and icatibant, respectively, P = 0.49). Of the 62 patients, 27 (44%) were admitted to hospital from the ED. In multivariate analysis, laryngeal involvement and progressive swelling at ED arrival were independently associated with admission (Odds ratio [95% confidence interval] = 6.2 [1.3–28.2] and 5.9 [1.3–26.5], respectively). A favorable course was observed in all patients. Three patients (5%) experienced a recurrence after angiotensin-converting enzyme inhibitor discontinuation after a median follow-up of 18 (11–30) months.Two severity criteria—laryngeal edema and the progression of the edema—were independent factors associated with likelihood of hospital admission. Appropriate specific treatments (plasma-derived C1-INH or icatibant) should be available in EDs to prevent possibly life-threatening complications.     

Evaluation of apical pouches in hypertrophic cardiomyopathy using cardiac MRI

The presence of apical pouches in hypertrophic cardiomyopathy (HCM) may portend poor prognosis. We sought to study if the use cardiac magnetic resonance imaging (CMR) improves the detection of apical pouches in HCM compared to echocardiography. A retrospective review was performed of all consecutive HCM patients with an apical pouch identified by CMR at Mayo Clinic from May 2004 to Sept 2011. Clinical data was abstracted and CMR and echocardiographic images were analyzed. There were 56 consecutive HCM patients with an apical pouch identified by CMR. The predominant morphological type was apical in 41 (73.2 %), followed by sigmoid in 6 (10.7 %), reversed curve in 6 (10.7 %) and neutral in 3 (5.4 %). Obstructive physiology or systolic anterior motion of the mitral valve leaflet was evident in 23 (41.1 %). Late gadolinium enhancement was present in 47 (87.0 %) patients. Apical pouches were detected in only 18 (32.1 %) patients on echocardiography. Even when intravenous contrast was used (29/56 patients), in 16/29 (55.2 %) pouches were missed on echocardiography. Pouch length and neck dimensions in systole and diastole, measured on CMR, were larger among those patients in whom pouches were detected on echocardiography suggesting only larger pouches can be identified on echocardiography. In the largest CMR series to date of apical pouches in HCM, we show that while apical pouches are most commonly seen in apical HCM, they can be found in other phenotypic variants. CMR is better suited for the evaluation of apical pouches compared to echocardiography even with the use of intravenous contrast. CMR is likely a better tool for evaluating the cardiac apical structures including apical pouches when clinically indicated.     

Ketamine Inhibits Presynaptic and Postsynaptic Nicotinic Excitation of Identified Cardiac Parasympathetic Neurons in Nucleus Ambiguus

Background: Ketamine increases both blood pressure and heart rate, effects commonly thought of as sympathoexcitatory. The authors investigated possible central nervous system actions of ketamine to inhibit cardiac parasympathetic neurons in the brainstem by inhibiting multiple nicotinic excitatory mechanisms.

Methods: The authors used a novel in vitro approach to study the effect of ketamine on identified cardiac parasympathetic preganglionic neurons in rat brainstem slices. The cardiac parasympathetic neurons in the nucleus ambiguus were retrogradely prelabeled with the fluorescent tracer by placing rhodamine into the pericardial sac. Dye-labeled neurons were visually identified for patch clamp recording. The effects of ketamine were tested on nicotine-evoked ligand-gated currents and spontaneous glutamatergic miniature synaptic currents (mini) in cardiac parasympathetic preganglionic neurons.

Results: Ketamine (10 [mu]m) inhibited (1) the nicotine (1 [mu]m)-evoked presynaptic facilitation of glutamate release (mini frequency, 18 +/- 7% of control; n = 9), and (2) the direct postsynaptic ligand-gated current (27 +/- 8% of control; n = 9), but ketamine did not alter the amplitude of postsynaptic miniature non-N-methyl-d-aspartate currents. [alpha] Bungarotoxin, an antagonist of [alpha]7 containing nicotinic presynaptic receptors, blocked ketamine actions on mini frequency (n = 10) but not mini amplitude.