Isolated left ventricular non compaction as possible cause of athletic training suspension: a preliminary study on screened athletes.

AIM: The aim of this paper was to determine the prevalence of isolated left ventricular noncomapction (ILVNC) in a sample of 150 athletes send by sports doctors to the Valmontone Hospital's Cardiology Division in a span of about three years, with particular interest in non-compacted segments evaluation. The prevention of cardiovascular complications occurring during sporting activity requires detection of pathologies most often clinically latent but whose first presentation can be sudden cardiac death. In Italy, the pre-participation screening program comprises family history and personal cardiac history, clinical examination and electrocardiography. Subjects with abnormalities are further investigated by stress test, echocardiography and laboratory investigations, and those with significant abnormalities are disqualified from sports training and competition. ILVNC results in multiple trabeculations in the left ventricular myocardium and it is postulated to be caused by intrauterine arrest of compaction of the myocardial fibres and meshwork, an important process in myocardial development. This cardiomyopathy should be considered one of the structural cardiac abnormalities responsible for sudden cardiac death. METHODS: There were 150 athletes seen in the Cardiology Division from 2007 to 2010 for an echocardiographic evaluation in order to clarify the nature of physical examination and/or electrocardiogram abnormalities. Echocardiographic diagnosis of ILVNC was based on criteria published by Jenni et al., and by Stölberger et al. RESULTS: Twenty-four of the 150 tested resulted positive for ILVNC (16.0%). This high prevalence is justified because it was a population originally selected because of electrocardiographic abnormalities. CONCLUSION: We believe that in case of unspecific ECG findings, it would be useful to perform echocardiographic examination in order to highlight structural defects. We also believe that it is very important to contemplate ILVNC between the causes of sudden death in young competitive athletes.

[Are catatonia and neuroleptic malignant syndrome related conditions?]. / Existe-t-il un lien entre catatonie et syndrome malin des neuroleptiques ?

INTRODUCTION: Catatonia and neuroleptic malignant syndrome are both conditions that can compromise survival and whose successful treatment depends on early diagnosis. OBJECTIVE: Distinguishing between these two conditions is difficult in a clinical setting and is further complicated by diagnostic criteria overlap. Are they both variations of a single disorder or two distinct conditions that happen to share certain characteristics? The goal of this paper is to review the available published data concerning the existence of a link between these two conditions and to specify the nature of the link between them. METHOD: We identified relevant articles from the PubMed registry by cross-referencing "catatonia" and "neuroleptic malignant syndrome". The articles returned were selected according to language (English and French) and publication date (before November 2007). RESULTS: Opinions are clearly divided concerning the existence of a link between these two conditions. The most commonly held opinion is that catatonia and neuroleptic malignant syndrome are two entities on the same spectrum. There are, however, no less than five different hypotheses concerning the nature of the link between them: first hypothesis: neuroleptic malignant syndrome is a drug-induced form of catatonia; second hypothesis: neuroleptic malignant syndrome is a drug-induced form of malignant catatonia; third hypothesis: neuroleptic malignant syndrome and malignant catatonia are one and the same; fourth hypothesis: catatonia is a risk factor for neuroleptic malignant syndrome; fifth hypothesis: neuroleptic malignant syndrome is a heterogeneous syndrome that includes both catatonic and non-catatonic responses to antipsychotic drugs. Other research maintains that catatonia and neuroleptic malignant syndrome are two distinct conditions. This point of view has fewer proponents, but benefits from historical, clinical and neurobiological studies that comfort this hypothesis. A careful clinical examination should in theory enable the distinction between these two entities and various neurobiological hypotheses are put forward to explain the differences between them. ANALYSIS AND DISCUSSION: The analysis of the data does not enable the elaboration of a single consensus on the existence of a link between catatonia and neuroleptic malignant syndrome. Additionally, the different hypotheses' level of scientific proof is insufficient to confirm or reject them. We only have at our disposal isolated case studies or studies with varying diagnostic criteria. CONCLUSION: A review of the literature does not enable us to confirm or invalidate a link between catatonia and neuroleptic malignant syndrome. However, answering this question would have direct consequences, since the suggestion of a link has led to the contraindication of neuroleptics for the treatment of catatonia, which contraindication has been extended on principle to the use of all newer antipsychotic medication. But since the link between catatonia and neuroleptic malignant syndrome has not been established according to scientific criteria, should the contraindication of atypical antipsychotic drugs be maintained in the treatment of catatonia?

A hand-carried cardiac ultrasound device in the outpatient cardiology clinic reduces the need for standard echocardiography.

OBJECTIVE: To assess the potential value and cost-effectiveness of a hand-carried ultrasound (HCU) device in an outpatient cardiology clinic. METHODS: 222 consecutive patients were prospectively enrolled in the study. When standard echocardiography (SE) was specifically indicated on the basis of clinical history, electrocardiogram and physical examination, the same cardiologist (level-2 or level-3 trained) immediately performed an HCU examination. The cardiologist then reassessed the clinical situation to confirm or cancel the SE request according to the information provided by HCU. The SE examination was performed by a sonographer and examined in a blinded fashion by a cardiologist expert in echocardiography. Findings from the two examinations were compared. RESULTS: HCU was performed in 108/222 patients, and a definite diagnosis was established in 34 of them (31%), making SE examination potentially avoidable. In the 74 patients with inconclusive HCU results and for whom SE was still indicated, the decision was mainly dictated by the lack of spectral Doppler modality in the HCU system. The overall agreement between HCU and SE for diagnosis of normal/abnormal echocardiograms was 73% (kappa = 0.4). On the basis of the potentially avoided SE examinations and the obviated need for a second cardiac consultation, a total cost saving of euro2142 per 100 patients referred for echocardiography was estimated. CONCLUSIONS: The use of a simple HCU device in the outpatient cardiology clinic allowed reliable diagnosis in one third of the patients referred for echocardiography, which translates into cost and time saving benefits.

[Clozapine-resistant schizophrenia related to an increased metabolism and benefit of fluvoxamine: four case reports]. / Inefficacité de la clozapine en rapport avec un métabolisme augmenté et intérêt de la fluvoxamine: à propos de quatre cas.

OBJECTIVE: Although clozapine currently remains the most effective option in treatment-resistant schizophrenia, approximately 40-70% of antipsychotic-resistant patients do not respond, or respond only partially, to clozapine. Because clozapine-resistant patients have limited alternative treatment options, in this study we propose a clozapine augmentation strategy with evidence-based support for some of them. BACKGROUND: Clozapine-resistance is often of metabolic origin. Clozapine is metabolized by N-oxidation and N-demethylation in the liver, predominantly by CYP450 1A2. Due to the influence of inhibitors, inducers, and genetic factors on CYP450 1A2-activity, there is extensive interindividual variability in clozapine plasma concentrations at a fixed dose. Consequently, monitoring of clozapine plasma concentrations is recommended. Several studies have suggested a significantly higher response rate at clozapine plasma concentration of less than 350 microg/l. Unfortunatly, some patients, especially young male smokers, do not achieve this minimum plasma concentration, even at doses higher than 900 mg/day and are nonresponders. CASE-REPORTS: We report the case of a 30 year-old smoker suffering from refractory schizophrenia, and responding poorly to treatments, including clozapine. Monitoring of the clozapine plasma concentration showed a very low level of clozapine, below the minimal effective dose of 350 microg/l. We initially suspected noncompliance with the treatment regime, but genetic analyses revealed another explanation: a gene polymorphism of the CYP450 1A2, principal enzyme that breaks down clozapine. The variability of CYP450 1A2 is explained by a gene polymorphism in intron 1. The A/A genotype confers high CYP450 1A2 inductivity in smokers. Certain smoking patients with A/A polymorphism have ultrarapid CYP450 1A2 activity, which causes the patient to metabolize clozapine too quickly. These patients do not respond to clozapine, even with doses higher than 900 mg/day. However, several factors can counter this elevated CYT activity, in particular fluvoxamine. The interaction between clozapine and fluvoxamine occurs via the inhibition of CYP450 1A2. Several studies have shown that administration of fluvoxamine to patients receiving clozapine therapy may increase the steady-state serum concentrations of clozapine by a factor of 5. Low doses of fluvoxamine inhibit the CYT activity, enough to raise the level of clozapine even when the dose of clozapine was reduced by 50%. The patient unfortunately developed a maniac episode during treatment with fluvoxamine, despite the absence of a previous history of bipolar illness, and we had to initiate treatment with lithium. Together, the three medications stabilized his condition satisfactorily for eight months. We describe three additional cases of treatment-refractory patients with schizophrenia and low-clozapine plasma levels despite high doses. They exhibited similar metabolic abnormality, as confirmed by a caffeine test, because plasma caffeine ratios reflect CYP450 1A2 activity. We then describe its correction, with low doses of fluvoxamine. These patients became responders when the plasma levels increased above the threshold. CONCLUSION: Consequently, we propose a therapeutic drug monitoring strategy. In the case of a clozapine-resistant schizophrenic patient, plasma clozapine levels should be tested. If the rate is normal, the resistance is not metabolic in origin. If the rate is low, a caffeine test should be done. If the results are normal, the patient is noncompliant with the treatment. If the caffeine test is abnormal, metabolic resistance is suspected. In such patients, we propose the addition of low-dose fluvoxamine while closely monitoring clozapine levels. Based on our experience, reducing the clozapine dose by 50% and prescribing 50 mg of fluvoxamine, so as to reach a minimum effective clozapine plasma concentration of more than 350 microg/l should provide an effective therapeutic strategy. This treatment may benefit the significant number of schizophrenic patients whose response to clozapine is hindered by metabolic hyper inductivity. Although this strategy may carry some risks for certain patients, the protocol we propose reduces the latter and the potential benefits should outweigh them.

[Treatment of clozapine-induced granulocytopenia with lithium (two observations)]. / Correction par le lithium des neutropénies induites par la clozapine (deux cas).

Despite the availability of new treatments, the antipsychotic effectiveness of clozapine has not been matched yet. Unfortunately, its regulation is limited by the side effects. The most detrimental is the hematologic toxicity (neutropenia and agranulocytosis) which requires a regular biological monitoring. Treatment with clozapine must be stopped in those cases of secondary granulocytopenia for about 3% of the patients. The current psychiatric drug lithium carbonate has an opposite effect: it can induce leukocytosis. Thus, lithium carbonate is administered in leukopenia, as well as in many hematologic and immunological diseases. However, few teams have used lithium in order to alleviate clozapine-induced granulocytopenia. We report here 2 patients who developed severe neutropenia (neutrophil count<1.5 yen 10 (9)/L) and for whom the use of lithium enabled us to continue the treatment by clozapine. The first patient had a granulocyte rate constitutionally low which rapidly decreased with clozapine. Thanks to the administration of lithium, he recovered quickly a normal blood cell count, which in fact was much higher than his normal rate. According to our research, it's the first time that lithium is reported to be so efficacious in a patient with such a low rate of granulocytes before treatment. It may be that clozapine is not used for those kinds of patients. The second patient developed granulocytopenia after one year of treatment with clozapine. The use of lithium increased so much the number of granulocytes that we continued the treatment with clozapine alone. After 4 months, there is no reappearance of granulocytopenia. We must take into account the partial and contradictory reports in the literature. However, if this result is confirmed, it could be of a high interest to extend the prescription of clozapine, the most effective current antipsychotic drug.

Perforated aneurysms of left side valves during active infective endocarditis complicating hypertrophic obstructive cardiomyopathy.

The most frequent site of vegetative lesion in patients with hypertrophic cardiomyopathy is anterior mitral leaflet, due to chronic endocardial trauma arising from systolic anterior motion. We describe three cases of serious infective endocarditis complicated lesions (vegetation, aneurysm and perforation) on aortic and mitral valves, in patients with obstructive hypertrophic cardiomyopathy. In particular, we observed how severe valvular damage and dysfunction, combined with particular hemodynamic conditions, are followed by adverse clinical outcome. We performed transthoracic echocardiogram and transoesophageal echocardiography studies to define morphologic and hemodynamic features of infection, deciding the proper therapy and we planned the echocardiographic follow-up.

Patent foramen ovale and its embolic implications.

This study investigates the usefulness of the echocardiographic characteristics of patent foramen ovale (PFO) in the stratification of stroke recurrence risk in patients with acute ischemic cerebral disease. Shunting at rest and a highly mobile fossa ovalis membrane are more frequently detected in stroke patients with PFO as the only identifiable cause of embolism. For PFO patients with both rest patency and membrane mobility > 6.5 mm, the risk of stroke/transient ischemic attack recurrence was 7.6% (95% CI, 0-18.0) at 12 months and 12.5% (95% CI, 0-26.1) at 24 months (p = 0.05). The association of both rest patency and high membrane mobility seems to identify those stroke patients with PFO at higher risk for further brain embolism.

Harmonic imaging with Levovist for transthoracic echocardiographic reconstruction of left ventricle in patients with post-ischemic left ventricular dysfunction and suboptimal acoustic windows.

BACKGROUND: Attempts to perform transthoracic 3-dimensional echocardiography (3DE) are often encumbered by poor definition of chamber borders in adult patients who have technically suboptimal acoustic windows. METHODS: To assess whether harmonic imaging (HI) and contrast agents can facilitate transthoracic 3DE assessment of the left ventricle, we used fundamental imaging (FI), HI alone, and HI coupled with the echo-enhancing contrast agent Levovist in 15 consecutive patients with post-ischemic left ventricular (LV) dysfunction and technically difficult windows. Dynamic 3DE image data sets were obtained at 5-degree angles (36 slices) from a transthoracic apical view. From these data a total of 240 myocardial segments were analyzed with the use of dynamic short-axis paraplane slices at basal, middle, and apical LV levels (standard 16 segment model). For border definition, each segment was scored in random sequence on the following scale by 2 independent investigators: 0 = not seen, 1 = suboptimal visualization, and 2 = well defined. RESULTS: Our results showed a significant increase in the number of well-visualized segments when harmonic mode combined with Levovist injection was compared with FI and HI alone. CONCLUSION: Harmonic imaging alone improves LV assessment by 3DE when compared with FI. Contrast imaging in which Levovist is added to HI further improves the capability of transthoracic tomographic 3DE in the visualization of LV myocardial segments. This could allow 3DE by transthoracic windows to be used more widely in adults for the evaluation of LV volume and function.