Low-dose fenfluramine significantly reduces seizure frequency in Dravet syndrome: a prospective study of a new cohort of patients.

BACKGROUND AND PURPOSE: Dravet syndrome (DS) is a severe, drug-resistant epilepsy. Fenfluramine has been reported to have a long-term clinically meaningful anticonvulsive effect in patients with DS. METHODS: This prospective, open-label study assessed the safety and effectiveness of low-dose fenfluramine in a new cohort of patients with DS. Following a 3-month baseline period, fenfluramine was added to each patient's current antiepileptic drug regimen at a dose of 0.25-1.0 mg/kg/day (max. 20 mg/day). The incidence of major motor seizures (tonic, clonic, tonic-clonic, atonic and myoclonic seizures lasting >30 s) in both the baseline and treatment periods was assessed via a seizure diary. Periodic echocardiographic examinations during the treatment period were used to assess cardiovascular safety. RESULTS: Nine patients (aged 1.2-29.8 years) enrolled in the study and were treated with fenfluramine for a median duration of 1.5 (range, 0.3-5.1) years. Median frequency of major motor seizures was 15.0/month in the baseline period. All patients demonstrated a reduction in seizure frequency during the treatment period with a median reduction of 75% (range, 28-100%). Seven patients (78%) experienced a ≥50% reduction in major motor seizure frequency. The most common adverse events were somnolence (n = 5) and anorexia (n = 4). No evidence of cardiac valvulopathy or pulmonary hypertension was observed. CONCLUSIONS: The effectiveness and safety of low-dose fenfluramine as an add-on therapy for DS in this new prospective cohort supports previous findings.

Impaired coronary flow reserve after a recent myocardial infarction: correlation with infarct size and extent of microvascular obstruction.

BACKGROUND: The exact relationship between the coronary flow reserve (CFR) and infarct size remains unknown. In this prospective study the relationship between the CFR both in the infarcted and remote myocardium and infarct size was investigated. Furthermore, the diagnostic value of the CFR to predict the extent of microvascular obstruction (MO) was evaluated. METHODS: In thirty patients the CFR was measured with a Doppler guide wire 6 ± 3 days after a first myocardial infarction (MI) in the infarct related and in a reference coronary artery. MO and infarct size were determined with magnetic resonance imaging. RESULTS: The CFR was inversely related to infarct size in the infarcted and remote myocardium (respectively, r=-0.60, p<0.01 and r=-0.62, p<0.01). In the infarcted myocardium the extent of MO was strongly related to the infarct size and was in a multivariate analysis the single significant determinant of the CFR and the hyperaemic flow. In the remote myocardium no relationship was present between infarct size and hyperaemic flow, but the baseline flow increased as the infarct size became larger (r=0.58, p<0.01). In a receiver operator characteristic (ROC) analysis, a CFR value ≤ 2 in the infarct related coronary artery offered the best sensitivity (65%) and specificity (71%) to detect the presence of MO (p<0.05). CONCLUSIONS: After MI, the CFR both in the infarcted and remote myocardium is inversely related to infarct size. In the infarcted myocardium, a CFR value ≤ 2 predicts the presence of MO with moderate sensitivity and specificity.

Effects of postural changes on cardiac function in healthy subjects.

AIMS: To analyse the response of Doppler measurements to increased venous return in middle-aged healthy subjects. METHODS AND RESULTS: Left ventricular pulsed Doppler parameters, colour M-mode of early left ventricular filling and septal mitral annulus velocities were measured at baseline and after leg lifting (n=24). Leg lifting resulted in increased stroke volume (69 +/- 14 to 74 +/- 14 ml, P<0.01) and peak systolic annulus velocity (6.8 +/- 1.3 to 7.3 +/- 1.1 cm/s, P<0.01). Leg lifting enhanced peak early (E) mitral flow (74 +/- 13 to 80 +/- 14 cm/s, P<0.01), flow propagation (53 +/- 10 to 59 +/- 13 cm/s, P<0.01) and E' diastolic mitral annulus velocity (10.8 +/- 2.2 to 11.7 +/- 2.0 cm/s, P<0.01). There was a shortening of E wave deceleration time (178 +/- 27 to 163 +/- 27 ms, P<0.01) and isovolumic relaxation time (76 +/- 11 to 68 +/- 10 ms, P<0.01). However, individual changes in Doppler parameters differed among subjects. CONCLUSIONS: Leg lifting improved myocardial function as manifested by increase in stroke volume, systolic annulus motion and acceleration of relaxation. Flow propagation velocity and diastolic mitral annulus velocities were influenced by the induced change in cardiac preload as well.

Aortic root diameter and nasal intermittent positive airway pressure treatment in Marfan's syndrome.

We report on a patient with Marfan's syndrome, with coexistent obstructive sleep hypopnea (OSH) and restrictive lung disease, complicated by respiratory insufficiency, who was successfully treated with nasal intermittent positive airway pressure (NIPPV) and oxygen. NIPPV therapy turned out to be effective on arterial gas exchange and well tolerated. Moreover, progressive dilatation of the aortic root was attenuated during NIPPV, but could, however, not be reversed. We hypothetized that (at least partially) a decrease of nocturnal intrathoracic pressures could explain this.

Magnetic resonance diagnosis of lipomatous hypertrophy of the atrioventricular grooves mimicking a tumour on echocardiography.

Echogenic structures in the atrioventricular grooves may cause diagnostic problems and may be misinterpreted as a tumour. Images of lipomatous hypertrophy of the atrioventricular grooves diagnosed by magnetic resonance but mimicking a tumour on echocardiography are presented.

Blurred vision, left bundle-branch block and cardiac failure.

We cared for a patient with progressive renal impairment who presented with blurred vision, QRS broadening and cardiac failure due to chronic cibenzoline intoxication. Treatment consisted of catecholamines and repetitive infusions of Ringer lactate. Cardiac function and symptoms recovered completely.

Echocardiographic diagnosis of platypnoea-orthodeoxia syndrome after blunt chest trauma.

Platypnea-orthodeoxia syndrome is a rare entity most often related to an interatrial right-to-left shunt. We report the case of a patient who developed platypnoea-orthodeoxia shortly after a blunt chest wall trauma. Definite diagnosis was obtained with transoesophageal echocardiography using contrast in upright and recumbent position. A Medline search did not reveal any other case report of the syndrome after chest wall injury.

Contrast-enhanced echocardiography: review and current role.

Contrast echocardiography has developed rapidly in the past decade. With the advent of more stable contrast agents and new ultrasound imaging techniques such as second harmonic imaging and transient response imaging, contrast echocardiography has evolved to a promising non-invasive perfusion technique. Myocardial contrast echocardiography is evolving from a qualitative to a quantitative technique, and from an intra-arterial to an intravenous approach. Assessment and quantification of myocardial perfusion in acute myocardial infarction, detection and evaluation of coronary artery disease and enhancement of endocardial border for improved definition of cardiac function are examples of novel applications of contrast echocardiography being developed.

[Cardiac myxoma in 13 patients]. / Myxoma cordis bij 13 patiënten.

OBJECTIVE: To gain insight into the occurrence, the manifestation and the treatment of cardiac myxoma. DESIGN: Retrospective. SETTING: The departments of Cardiology and Cardiac Surgery of Middelheim General Hospital, Antwerp, Belgium. PATIENTS AND RESULTS: Thirteen patients in the period 1985-1995 were subjected to surgical resection of a cardiac myxoma. In accordance with earlier studies, most patients were middle-aged and female. The site of predilection was the left atrium. Cardiac auscultation suggested mitral valve stenosis and insufficiency in three and five patients, respectively; in only one case was the specific 'tumour plop' heard. Cardiac symptoms were atypical thoracic pain (4 times), syncopes (3) and effort dyspnoea (7). Although embolism is described in the literature in 20-70% of the cases, it occurred in only three patients of this group. General symptoms were observed in only seven patients, as against 90% in earlier studies: they were elevated sedimentation rate in five (one also polycythaemia and leucocytosis) and abnormal fatigue in two (one also anorexia) patients. In all 13, the diagnosis of 'intracardiac mass' was made on the basis of ultrasonography. In six of 11 patients who subsequently underwent coronary roentgenography, neovascularization was visualized. All 13 tumours were resected successfully, after which in ten cases a dacron patch was implanted at the level of the interatrial septum. In addition, two patients underwent coronary bypass surgery. Postoperatively, atrial flutter (two patients), atrial fibrillation (one) and fatal cerebral bleeding (one) were observed. The other patients suffered no recurrences. CONCLUSION: Cardiac myxoma is a rare tumour which in general can be accurately diagnosed on the basis of ultrasonography and which almost always can be cured by surgical excision.