Effects of 5 days of head-down bed rest, with and without short-arm centrifugation as countermeasure, on cardiac function in males (BR-AG1 study).

This study examined cardiac remodeling and functional changes induced by 5 days of head-down (-6°) bed rest (HDBR) and the effectiveness of short-arm centrifugation (SAC) in preventing them in males. Twelve healthy men (mean age: 33 ± 7) were enrolled in a crossover design study (BR-AG1, European Space Agency), including one sedentary (CTRL) and two daily SAC countermeasures (SAC1, 30 min continuously; SAC2, 30 min intermittently) groups. Measurements included plasma and blood volume and left ventricular (LV) and atrial (LA) dimensions by transthoracic echocardiography (2- and 3-dimensional) and Doppler inflows. Results showed that 5 days of HDBR had a major impact on both the geometry and cardiac function in males. LV mass and volume decreased by 16 and 14%, respectively; LA volume was reduced by 36%; Doppler flow and tissue Doppler velocities were reduced during early filling by 18 and 12%, respectively; and aortic flow velocity time integral was decreased by 18% with a 3% shortening of LV ejection time. These modifications were presumably due to decreased physiological loading and dehydration, resulting in reduced plasma and blood volume. All these changes were fully reversed 3 days after termination of HDBR. Moreover, SAC was not able to counteract these changes, either when applied continuously or intermittently.

Migraine with aura and silent brain infarcts lack of mediation of patent foramen ovale.

BACKGROUND AND PURPOSE: Population-based studies have shown a heightened prevalence of clinically silent brain infarcts in subjects who have migraine with aura (MA). We sought to determine whether this association could be confirmed in young patients with cryptogenic ischemic stroke, and explored the role of patent foramen ovale (PFO) as a potential underlying mechanism. METHODS: Patients were selected from a registry of young patients consecutively treated for ischemic stroke in a tertiary university hospital among those without definite cause of stroke. Patients with PFO were matched for age and gender with patients with normal atrial septum. Migraine and MA were evaluated after patient selection and matching. Silent brain infarcts were independently evaluated on MRI. RESULTS: We included 100 patients [60 men; mean age (SD), 44.8 years (8.3)], 50 patients with PFO. We found silent brain infarcts in 36 patients and MA in 13 patients. MA was more frequent in patients with silent brain infarcts than in patients without silent brain infarcts (25.0% vs. 6.3%; OR, 5; 95% CI, 1.4-17.6; P = 0.01). Traditional cardiovascular risk factors were not associated with silent brain infarcts. PFO was neither associated with MA (OR, 1.7; 95% CI, 0.5-5.3) nor silent brain infarcts (OR, 0.7; 95% CI, 0.3-1.5). The association of MA with silent brain infarcts was not altered after adjustment for PFO. CONCLUSION: Findings suggest that silent brain infarcts in young patients with cryptogenic stroke is associated with MA. We found no evidence for a mediating effect of PFO on this association.

Patent foramen ovale and ischemic stroke.

Patent foramen ovale (PFO) is a common finding in healthy subjects and has not been associated with increased risk of ischemic stroke in population-based cohort studies. Nevertheless, case-control studies have consistently shown an increased prevalence of PFO in cryptogenic stroke, suggesting that PFO might be a cause of stroke. The risk of stroke recurrence in patients with cryptogenic stroke and PFO is low under aspirin therapy but may be substantially higher in patients with an associated atrial septal aneurysm (ASA). The mechanisms of stroke associated with PFO or ASA are uncertain. Paradoxical embolism through the PFO is rarely documented. The optimal treatment for secondary prevention in patients with cryptogenic stroke and PFO is still uncertain and debated. A randomized controlled trial failed to demonstrate the superiority of transcatheter PFO closure over medical therapy. Whether anticoagulation is superior to aspirin should be tested in a randomized controlled trial.

Etiologic investigation of ischemic stroke in young adults.

OBJECTIVES: We attempted to classify causes of ischemic stroke in young adults using a progressive diagnostic algorithm and the ASCO (atherosclerosis, small-vessel disease, cardiac source, other cause) classification system. METHODS: Patients aged 16-54 years consecutively treated for acute ischemic stroke in a tertiary stroke unit were included in this retrospective analysis. Causes of stroke were classified using the ASCO system, which assigns a graded level of likelihood to each potential cause in individual patients. The initial etiologic workup included brain imaging, magnetic resonance or CT angiography of cerebral and cervical vessels, EKG, and routine blood studies. Patients without a definite cause of ischemic stroke after initial evaluation underwent transesophageal echocardiography. RESULTS: We included 318 patients (195 men and 123 women); 131 patients were aged 16-44 years, and 187 were aged 45-54 years. A definite cause of stroke (ASCO grade 1) could be identified in 145 patients (45.5%). An uncertain cause of stroke (ASCO grade 2) was found in 59 (18.5%) further patients. Most (130 of 145) definite causes were identified by initial evaluation. The 2 major definite or uncertain causes of stroke were patent foramen ovale associated with atrial septal aneurysm (PFO-ASA) (20 of 131 [15.3%]) and dissection of the cervical or cerebral artery (19 of 131 [14.5%]) in patients aged 16-44 years and large-vessel atherosclerosis (37 of 187 [19.8%]) and PFO-ASA (23 of 187 [12.3%]) in patients aged 45-54 years. CONCLUSIONS: Our findings suggest that PFO-ASA may be a major cause of ischemic stroke in young adults.

DBH deficiency in an elderly patient: efficacy and safety of chronic droxidopa.

We describe the effects of chronic droxidopa in a patient with Dopamine beta-hydroxylase deficiency diagnosed at the age of 73. Investigations were performed to assess sympathetic activity (MIBG scintigraphy, catecholamines) and cardiovascular droxidopa safety.

The importance of imaging assessment before endovascular repair of thoracic aorta.

Indications for and experience with placement of endovascular stent grafts in the thoracic aorta are still evolving. Recent advances in imaging technologies have drastically boosted the role of pre-procedural imaging. The accepted diagnostic gold standard, digital subtraction angiography, is now being challenged by the state-of-the-art computed tomography angiography (CTA), magnetic resonance angiography (MRA) and trans-oesophageal echocardiography (TEE). Among these, technological advancements of multidetector computed tomography (MDCT) have propelled it to being the default modality used, optimising the balance between spatial and temporal resolutions and invasiveness. MDCT angiography allows the comprehensive evaluation of thoracic lesions in terms of morphological features and extent, presence of thrombus, relationship with adjacent structures and branches as well as signs of impending or acute rupture, and is routinely used in these settings. In this article, we review the current state-of-the-art radiological imaging for thoracic endovascular aneurysm repair (TEVAR), especially focusing on the role of MDCT angiography. After analysing the technical aspects for optimised imaging protocols for thoracic aortic diseases, we discuss pre-procedural determinants of candidacy, and how to formulate interventional plans based on cross-sectional imaging.

Prevalence of atrial septal abnormalities in older patients with cryptogenic ischemic stroke or transient ischemic attack.

OBJECTIVE: To evaluate the association of atrial septal abnormalities--patent foramen ovale (PFO), atrial septal aneurysm (ASA), or the combination of both (PFO+ASA)--with cryptogenic stroke or transient ischemic attack (TIA) in older patients. METHODS: We examined the prevalences of PFO, ASA, and PFO+ASA in 132 consecutive patients aged 55 years or more who underwent transesophageal echocardiography (TEE) for evaluation of ischemic stroke or TIA. We compared patients with cryptogenic stroke/TIA and those with stroke/TIA of known cause. RESULTS: PFO+ASA was more common in patients with cryptogenic stroke/TIA than in patients with stroke/TIA of known cause (12/62 or 19% vs. 2/70 or 3%; adjusted odds ratio, 7.4; 95% CI, 1.4-38.2). Differences between groups for isolated PFO, and isolated ASA were not significant. The association of PFO+ASA with cryptogenic stroke/TIA was confirmed in the subgroup of patients aged 75 years or more (odds ratio, 15.0; 95% CI, 1.5-146.7). CONCLUSION: This study indicates a significant association of PFO+ASA with cryptogenic stroke or TIA in older patients.

NMR and cDNA array analysis prior to heart failure reveals an increase of unsaturated lipids, a glutamine/glutamate ratio decrease and a specific transcriptome adaptation in obese rat heart.

Obesity is a risk factor for heart failure through a set of hemodynamic and hormonal adaptations, but its contribution at the molecular level is not clearly known. Therefore, we investigated the kinetic cardiac transcriptome and metabolome in the Spontaneous Hypertensive Heart Failure (SHHF) rat. The SHHF rat is devoid of leptin signaling when homozygous for a mutation of the leptin receptor (ObR) gene. The ObR-/- SHHF rat is obese at 4 months of age and prone to heart failure after 14 months whereas its lean counterpart ObR-/+ is prone to heart failure after 16 months. We used a set of rat pangenomic high-density macroarrays to monitor left ventricle cardiac transcriptome regulation in 4- and 10-month-old, lean and obese animals. Comparative analysis of left ventricle of 4- and 10-month-old lean rat revealed 222 differentially expressed genes while 4- and 10-month-old obese rats showed 293 differentially expressed genes. (1)H NMR analysis of the metabolome of left ventricular extracts displayed a global decrease of metabolites, except for taurine, and lipid concentration. This may be attributed to gene expression regulation and likely increased extracellular mass. The glutamine to glutamate ratio was significantly lower in the obese group. The relative unsaturation of lipids increased in the obese heart; in particular, omega-3 lipid concentration was higher in the 10-month-old obese heart. Overall, several specific kinetic molecular patterns act as a prelude to heart failure in the leptin signaling deficient SHHF obese rat.

Endovascular treatment of thoracic dissection.

Type A aortic dissection remains fatal if untreated. Although classical medical therapy for type B dissection is considered the therapy of choice in uncomplicated cases, the paradigm is changing as greater experience is accrued with endovascular treatments and technical advances improve the long-term outlook. Diagnosis is also becoming more sophisticated, allowing greater appreciation of the anatomy of dissections and improving the knowledge base as their natural history is assessed.

[Percutaneous closure of three septal defects by two Amplatz occluders implanted during the same procedure]. / Fermeture percutanée de 3 communications interauriculaires par 2 dispositifs d'Amplatz implantés au cours d'un même cathétérisme.

Multiple atrial septal defects can be closed by interventional catheterisation. The procedure requires an accurate morphological evaluation: number of defects, distance from their edges to the main cardiac structures, resistance of the septum. The authors report the case of a 63 year old woman presenting with cardiac failure in whom 3 atrial septal defects were diagnosed. All 3 defects were successfully closed by the implantation of two Amplatz devices. Control echocardiography at 6 months showed the occluders in a normal position with no residual shunt and the patient was asymptomatic.

[Endografts (or stent-grafts) and diseases of the descending thoracic aorta]. / Endoprothèses (ou stent-grafts) et pathologies de l'aorte thoracique descendante.

The endovascular treatment of aorta diseases with S-Graft is considered as an alternative to surgery, especially interesting in patients with severe comorbidities. Indeed, the mid-term morbidity and mortality are comparable to surgery in relatively large series, and S-Graft implantation appeared as a safe, less invasive and efficient treatment for different affections of the thoracic aorta. This article reviews technical aspects, indications and results of endovascular repairs of thoracic aorta lesions. We will also assess the advantages and limitations of S-Graft therapy.

[Cardiac cellular therapy: from cells to the first clinical uses]. / Thérapie cellulaire cardiaque: des cellules aux premières indications cliniques.

Despite the improvement in revascularisation techniques, coronary artery disease remains the principal aetiology of cardiac failure in developed countries. The therapeutic management of cardiac failure has been improved over recent years, yet cardiac failure is still associated with significant morbidity and mortality. As cardiac transplantation lacks donors, techniques that allow myocardial regeneration represent an attractive alternative. To date, several types of cells are under study and are suitable for implantation into infarcted myocardium (myoblasts, medullary stem cells...). Following good preclinical study results, the first human cell therapy trials, using the intramyocardial route, have begun, in the course of aorto-coronary bypass surgery in patients with chronic ischaemic cardiopathy and little altered left ventricular function, and then in those with ventricular dysfunction. Different modes of administration of these cell therapy products are under study and could be envisaged in clinical situations such as just after infarction in order to improve ventricular remodelling with an intracoronary injection technique. As for every new treatment, there are numerous problems to resolve, from understanding the relevant mechanisms of cellular transplantation, to the secondary effects that it could entail. Nevertheless, cardiac cellular transplantation is expanding rapidly and with the evolution of techniques it allows a glimpse of a new field of treatment for cardiac failure.

[Echocardiography and the painful aorta]. / Echocardiographie et aorte douloureuse.

The acute painful aortic syndrome is a clinical enity observed in four conditions: dissection, intramural haematoma, penetrating atheromatous ulcer and aneurysm. The diagnosis is based on three imaging techniques: echocardiography, CT scan and magnetic resonance imaging. They have displaced angiography which is incomplete and even dangerous in some cases. Their sensitivity and specificity are comparable in terms of diagnosis. However, each has a specificity. Transthoracic and transoesophageal echocardiography are useful in the diagnosis, the quantification and analysis of the mechanism of aortic regurgitation which may complicate dissection. CT scan visualises the collateral arteries, investigates the physiopathological mechanisms of poor perfusion syndromes and detects parietal fissuration. Magnetic resonance imaging is better adapted to the study of stable forms. In conclusion, transoesophageal echocardiography is a rapid and reliable diagnostic method, it can be used as the investigation of first intention and is essential in patient management. The use of other imaging modes is only required in some cases. The choice, guided by the clinical history, depends on its aptitude to complete the missing or partial data of transoesophageal echocardiography.

Acute traumatic aortic rupture: a comparison of surgical and stent-graft repair.

OBJECTIVE: The study's objective was to comparatively evaluate surgery and stent-graft repair of acute or subacute traumatic aortic rupture. METHODS: A total of 76 patients (14-76 years old; mean, 37 years; male/female ratio, 63/11) with a traumatic aortic injury were admitted to our hospital between 1981 and 2003. Six patients died within 1 to 9 days of another associated severe traumatic lesion. The 70 remaining patients were divided according to the type of rupture repair. In group 1, 35 patients were treated surgically: 28 with immediate repair and 7 with delayed repair (average time interval 66 days, 5-257 days). In group 2, 29 patients were treated with stent grafting of the aortic isthmus. In group 3, 6 patients with minor aortic lesions were treated medically with a close follow-up. RESULTS: In the 28 patients treated surgically in the emergency department, the mortality and paraplegia rates were 21% and 7%, respectively. No death or paraplegia was observed in the group with delayed surgical repair. With stent grafting, complete exclusion of the pseudoaneurysmal sac was observed in all patients. Except for 1 iliac rupture treated during the same procedure, there was no major morbidity or mortality during the mean follow-up of 46 months (13-90 months). No major complication was observed in group 3. CONCLUSIONS: In stable rupture of the aorta, initial conservative treatment is safe and allows management of the major associated lesions. Stent grafting of the aortic isthmus is a valuable therapeutic alternative to surgical repair, especially in patients considered high risk for conventional thoracotomy.

[Obesity and cardiac failure]. / Obésité et insuffisance cardiaque.

Obesity alone is the cause of 11% of cases of cardiac failure in men and 14% of cases in women in the United States. The frequency of obesity continues to rise in our country, 41% of our compatriots being obese or overweight. It is expected that obesity will become an important cause of cardiac failure in the coming years. The Framingham study showed that, after correction for other risk factors, for every point increase in body mass index, the increase in risk of developing cardiac failure was 5% in men and 7% in women. There are three physiopathological mechanisms to explain the adverse effects of obesity on left ventricular function: an increase in ventricular preload secondary to increased plasma volume induced by the high fatty mass; an increase in left ventricular afterload due to the common association of hypertension generated by activation of the sympathetic nervous system by hyperinsulinism; and systolic and diastolic dysfunction due to changes in the myocardial genome and coronary artery disease induced by risk factors of atherosclerosis aggravated by obesity. The adipocyte also secretes a number of hormones which act directly or indirectly on the myocardium: angiotensin II, leptin, resistin, adrenomedulin, cytokines. These haemodynamic and hormonal changes profoundly modify the genetic expression of the myocardium in obesity, favourising hypertrophy of the myocyte and the development of interstitial fibrosis. Whether it be eccentric in the absence of hypertension or concentric when hypertension is associated with obesity, left ventricular hypertrophy, although normalising left ventricular wall stress, has adverse consequences causing abnormal relaxation and decreased left ventricular compliance. Therefore, in obese patients, two forms of cardiac failure may be observed. The more common is due to diastolic dysfunction, obesity being one of the principal causes of cardiac failure with preserved systolic function. Cardiac failure due to systolic dysfunction is less common and may be observed in cases with inappropriate left ventricular hypertrophy which does not normalise abnormal left ventricular wall stress leading to cardiomyopathy, and in cases with associated coronary artery disease. Whatever the underlying mechanism, the diagnosis of cardiac failure is made more difficult by obesity. From the prognostic point of view, in the global population of patients with cardiac failure, obesity improves survival because it counteracts the adverse effect of cachexia; however, obesity increases the risk of sudden death. In fact, obesity is associated with dynamic change in QT interval. In cases of cardiac failure secondary to obesity-related cardiomyopathy, loss of weight leads to an improved functional status and a reduction of left ventricular remodelling and an increase of the ejection fraction.

[Towards a new management of acute traumatic aortic ruptures]. / Vers une nouvelle prise en charge des ruptures traumatiques aiguës de l'isthme aortique.

PURPOSE: The aim of this study was to evaluate the feasibility and safety of endovascular repair in acute traumatic aortic rupture on the basis of our experience with 16 patients. MATERIALS AND METHODS: From January 1996 to December 2001,16 patients, with a mean age 36 years, underwent repair of traumatic rupture of the aorta with the use of stent-grafts. All patients presented with coexisting injuries and 9 of 16 patients were hemodynamically unstable because of other injury. After a delay ranging from 9 to 245 days (mean 78 days), aortic stent-grafting was performed by a multidisciplinary team. All patients had regular follow-up with spiral CT and transesophageal echocardiogram. RESULTS: Stent-graft placement was successful in all patients with exclusion of false aneurysm. The duration of the procedure was about 120 min and mechanical respiratory assistance could be removed immediately in 80% of patients. Mean stay in the intensive care unit was 24 hours. One complication was noted: compression of the left main stem bronchus successfully treated with endoprosthesis. Maximum follow-up was 7 years. CONCLUSION: Endovascular stent-graft repair is a valuable technique and is emerging as an alternative technique for treating thoracic aortic injury in patients in whom coexisting injury increases the surgical risk.

[Effects of bradykinin in the cardiovascular effects of angiotensin-converting enzyme inhibitors]. / Effets de la bradykinine dans les effets cardiovasculaires des inhibiteurs de l'enzyme de conversion.

The role of bradykinin in the cardiovascular effects of angiotensin converting enzyme inhibitors remains difficult to establish. On their haemodynamic effects, bradykinin acts during their acute administration, participating in their vasodilatation action, while during their chronic administration they act slightly or not at all. On their trophic effects, the action of the tissue kallikrein-kinin system, suggested by the results of animal experimentation, is yet to be demonstrated in man. For their effects on cardiovascular morbidity and mortality the role of bradykinin remains under discussion. Nevertheless, besides ACE inhibitors, the other therapeutic agents which increase the levels of bradykinin, such as neutral endopeptidase inhibitors, have a significant field of development in the course of cardiovascular pathologies.