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Crohn disease (CD) is an inflammatory bowel disease whose pathogenesis involves inappropriate immune responses toward gut microbiota on genetically predisposed backgrounds. Notably, CD is associated with single-nucleotide polymorphisms affecting several genes involved in macroautophagy/autophagy, the catabolic process that ensures the degradation and recycling of cytosolic components and microorganisms. In a clinical translation perspective, monitoring the autophagic activity of CD patients will require some knowledge on the intrinsic functional status of autophagy. Here, we focused on monocyte-derived dendritic cells (DCs) to characterize the intrinsic quantitative features of the autophagy flux. Starting with DCs from healthy donors, we documented a reprogramming of the steady state flux during the transition from the immature to mature status: both the autophagosome pool size and the flux were diminished at the mature stage while the autophagosome turnover remained stable. At the cohort level, DCs from CD patients were comparable to control in term of autophagy flux reprogramming capacity. However, the homozygous presence of ATG16L1 rs2241880 A>G (T300A) and ULK1 rs12303764 (G/T) polymorphisms abolished the capacity of CD patient DCs to reprogram their autophagy flux during maturation. This effect was not seen in the case of CD patients heterozygous for these polymorphisms, revealing a gene dose dependency effect. In contrast, the NOD2 rs2066844 c.2104C>T (R702W) polymorphism did not alter the flux reprogramming capacity of DCs. The data, opening new clinical translation perspectives, indicate that polymorphisms affecting autophagy-related genes can differentially influence the capacity of DCs to reprogram their steady state autophagy flux when exposed to proinflammatory challenges. Abbreviation : BAFA1: bafilomycin A1, CD: Crohn disease; DC: dendritic cells; HD: healthy donor; iDCs: immature DCs; IL: interleukin; J: autophagosome flux; LPS: lipopolysaccharide; MHC: major histocompatibility complex; nA: autophagosome pool size; SNPs: single-nucleotide polymorphisms; PCA: principal component analysis; TLR: toll like receptor; τ: transition time; TNF: tumor necrosis factor.

Juvenile idiopathic arthritis is the most common chronic rheumatic disease in children, and its etiology remains poorly understood. Here, we explored four families with early-onset arthritis carrying homozygous loss-of-expression mutations in LACC1. To understand the link between LACC1 and inflammation, we performed a functional study of LACC1 in human immune cells. We showed that LACC1 was primarily expressed in macrophages upon mTOR signaling. We found that LACC1 deficiency had no obvious impact on inflammasome activation, type I interferon response, or NF-κB regulation. Using bimolecular fluorescence complementation and biochemical assays, we showed that autophagy-inducing proteins, RACK1 and AMPK, interacted with LACC1. Autophagy blockade in macrophages was associated with LACC1 cleavage and degradation. Moreover, LACC1 deficiency reduced autophagy flux in primary macrophages. This was associated with a defect in the accumulation of lipid droplets and mitochondrial respiration, suggesting that LACC1-dependent autophagy fuels macrophage bioenergetics metabolism. Altogether, LACC1 deficiency defines a novel form of genetically inherited juvenile arthritis associated with impaired autophagy in macrophages., Competing Interests: Disclosures: S. Georgin-Lavialle reported personal fees from SOBI, non-financial support from Novartis, and personal fees from BMS outside the submitted work. F. Bleicher reported a patent to FR1655539 pending. J. Reboulet reported a patent to FR1655539 issued. S. Merabet reported a patent to FR1655539 pending. T. Henry reported personal fees from SOBI and grants from SOBI outside the submitted work. No other disclosures were reported., (© 2021 Omarjee et al.)

Mountain endurance running has increased in popularity in recent years. Thus the aim of the present study was to determine if maximal oxygen uptake (VO2max) and energy cost of running (Cr) measured during level and uphill running are associated. Ten high level male endurance mountain runners performed three maximal oxygen uptake tests at three slope conditions (0, 12.5 and 25%). Metabolic data, step frequency (SF) and step length (SL) were recorded. No significant differences were found in VO2max (63.29 (±3.84), 63.97 (±3.54) and 63.70 (±3.58) mlO2/kg(-1)/min(-1)) or associated metabolic data at 0, 12.5 and 25% slope respectively. High intra-individual correlations were found between metabolic data measured in the three conditions. The energy cost of running was significantly different between slopes (0.192 (±0.01), 0.350 (±0.029) and 0.516 (±0.035) mlO2/kg(-1)/min(-1), p < 0.01), 0, 12.5 and 25% respectively. However, Cr0% was not correlated with either Cr25% or Cr12.5% (rs = 0.09 and rs = 0.10), in contrast, Cr25% and Cr12.5% were correlated (rs = 0.78). Step length was positively correlated with speed under the three slope conditions. Step frequency was significantly lower at 25 compared to 12.5 and 0% slope. We found that the maximum aerobic power did not differ between level and graded treadmill tests. However, the increase in Cr on the inclined versus level conditions varied between subjects. None of the measured anthropometric or kinematic variables could explain the higher increase in Cr of some subjects when running uphill. Thus, a short graded (5min at 12.5%) running test should be performed at a submaximal velocity (around 40% of level vVO2max) to enhance understanding of an endurance runner's uphill capability. Key pointsIn elite endurance mountain runners, there is no difference in VO2max values between level and uphill running.In a homogeneous group of mountain runners, uphill Cr is not associated with level Cr.To assess performance potential of endurance mountain runners, a standardized uphill running protocol should be performed.

Cannabis is the most consumed drug in France, particularly in young adults. Few reports have suggested a causal role of cannabis in the development of cardiovascular events. We describe one case of 26-year-old man, cannabis and tobacco smoker, admitted with recurrent ischemic stroke cause by post-myocardial infarction left ventricular thrombus. Coronary arteries were angiographicaly normal and etiological tests were negative. We suggest the possible relationship between marijuana use with coronary heart disease., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Background: Search and rescue helicopters from the French navy conduct ambulance and search and rescue missions near the western coast of the French Britain. The team on board includes military doctor and paramedic. Operations in this area are challenging due to long distances and severe weather conditions., Methods: We studied retrospectively 205 search and rescue missions from 2000 to 2007 with special emphasis on acute heart disease and operative conditions., Results: 12.2% of the missions (25/205) concern acute heart disease dominated by myocardial infarction elevation myocardial infarction. All of the patients are male. Most of them are seafarers and the others come from ferries with a median age of 53.4 years. Sixty-two percent of the missions were carried in darkness. The median range is about 80 nautical miles. Two patients died during search and rescue missions. All patient are hospitalized., Conclusion: Ambulance and search and rescue mission near the western coasting of the French Britain are a challenge. Using a heavy helicopter from French Navy was the best way to carry medical treatment to seafarers and passengers of ferries suffering from acute heart disease.

We describe a case of a young patient admitted for recurrent ischemic stroke caused by a papillary fibroelastoma of the mitral valve and a hyperhomocysteinemia. A papillary fibroelastoma is a benign cardiac tumor which can be associated with serious embolic complications. A moderate plasma level of hyperhomocysteinemia is considered as a risk factor of ischemic stroke. The authors suggest that this association increases the risk of ischemic stroke in their patient. The tumor was surgically removed to avoid new embolic events associated with a vitamin B supplementation. After surgery and acid folic supplementation, no recurrence was observed.

Spondyloarthropathies are associated with a greater cardiovascular risk than expected based on the cardiac lesions known to occur in these diseases. The prevalence of several conventional risk factors is high in spondyloarthropathy patients, and chronic inflammation also contributes to premature plaque formation. In addition, susceptibility genes for spondyloarthropathies may be associated with an increased risk of cardiovascular disease. Finally, several drugs used to treat spondyloarthropathies may contribute to the occurrence of cardiovascular events. A careful evaluation of the cardiovascular risk profile is a key component of the management of patients with spondyloarthropathies.

The electrocardiographic appearances and the significance of right bundle branch block were described at the beginning of the 20th century. Typical appearances include prolongation > 0.12 s of the QRS complex, RR' or rR' or Rr' appearances in V1 and widened S waves in the leads exploring the left ventricle (SI, aVL, V5 and V6). A delay in the appearance of the intrinsic deflection > 0.08 s may also be observed in the right precordial leads and negative T waves with ST depression may be seen in V1 and sometimes in V2. Left axis deviation of the QRS complex greater than - 45 degrees suggests associated left anterior hemiblock. Right axis deviation beyond + 120 degrees is equivocal. The principal differential ECG diagnosis is the Brugada syndrome, a familial arrhythmogenic autosomal dominant cardiomyopathy of variable penetration. This diagnosis is suggested when ECG abnormalities are observed in patients with a personal or family history of sudden death. Right bundle branch block only seems to have haemodynamic consequences in cardiac failure with associated asynchrony of the left ventricle or in certain cases of right ventricular dilatation encountered in congenital heart disease. The prognosis of right bundle branch block in the absence of underlying cardiac disease is good but it may be poor in other cases, particularly coronary artery disease. Moreover, the prognosis of right bundle branch block to complete atrioventricular block is rare in the absence of associated cardiac disease.

Unlabelled: Multislice computed tomography (MSCT) is a non-invasive and validated technique to detect coronary stenoses. Some questions remain about its accuracy to detect coronary stenoses (CS), especially for asymptomatic patients (P) when a prior stress test isn't conclusive., Methods: MSCT was performed among 45 asymptomatic men (mean age: 58,3 +/- 16), with a high ten year risk of fatal cardiovascular disease (SCORE 2003 data for low-risk regions of Europe), without any previous coronary history and with previous non conclusive exercise testing. When significant (> 50%) CS was suspected at MSCT, an angiocoronarography (AC) was done., Results: Eighteen MSCT were normal, unsignificant CS (< 50%) were detected on 14 MSCT and significant coronary stenoses (SCS) for 13 P. Among this 13 P, 19 SCS were identified: 2 SCS of left main coronary artery (CA), 9 of the left descending CA, 6 of the right CA and 2 of the left circumflex CA. 13 CS were confirmed at AC. Finally, because of critical angiographic lesions +/- ischemia at nuclear tomoscintigraphy (NT), 9 P had coronary revascularization (7 catheter based, 2 surgical bypass), 4 P had medical treatment., Discussion: Benefits of this preliminary study are obvious: 9 coronary revascularization/45 P. However, the place of MSCT for the screening of CS is uncertain, but may be usefull as a complement for the screening of coronary arterial disease.

Introduction: The association of vasoplegic shock and myocardial infarction in a patient under iloprost treatment for critical ischemia of the lower limbs has not previously been reported., Observation: A 56 year-old man suffering from type 2 diabetes, hypertension and dyslipidemia developed critical ischemia of the right leg and was treated with iloprost. On the 19th day of infusion, he developed a vasoplegic shock with myocardial infarction. The shock resolved and he recovered from the infarction., Discussion: This case report indicates the need for reinforced blood pressure and electrocardiographic monitoring in diabetes patients treated with iloprost.

Aerobatics is an aerial sport which has many physiological constraints, principally cardiovascular, with a risk if not adapted of sudden mid-air incapacity which could jeopardise aviation safety, and thus justifies the selection and surveillance of pilots. The aeronautical constraints during flight are multiple, related to the environment traversed, how the aircraft functions and its movements. Those which cause accelerations (+G in particular) pose the problem of haemodynamic tolerance because they can induce loss of consciousness due to cerebral hypoxia. Tolerance of acceleration varies among individuals; it can be improved with training, certain protective manoeuvres, and is reduced by hypoxia, certain medications, dehydration and heat. Moreover, in aerobatics certain tricks require manoeuvres which reduce this tolerance to +G accelerations. This is the "push-pull" effect (&#95;G acceleration immediately followed by +G acceleration). This leads to a risk of sudden loss of consciousness with a load factor much lower than that which the pilot knows he is capable of tolerating. Besides the haemodynamic effects, the existence of an actual acceleration cardiomyopathy has been suggested but has not been proven in man. Finally, while changes in cardiac rhythm during accelerations are usual and relate to changes in vaso-sympathetic balance, ventricular and supra-ventricular rhythm disturbances are rare and are related to the intensity and duration of the acceleration.

The association of cardiac tamponade and pulmonary embolism has not previously been described. We report the case of a patient, who presented with such an association, due to an underlying pulmonary carcinoma. When a major pericardial effusion is associated with pulmonary hypertension, some echocardiographic signs of tamponade may appear, such as a moderate right ventricular collapse, or the absence of a paradoxical septum. The presence of pulmonary hypertension in this context of tamponade may have paradoxically saved the life of this patient.

The chloroquine is the mainly and most frequently drug used as antimalaric in the world, in spite of the extension of resistance phenomena. Besides, the chloroquine is also commonly indicated in rheumatology and dermatology as a chronic treatment of some connective tissue disease. The chloroquine has three main cardiovascular effect: membrane stabilizer, direct negative inotropic effect and direct arterial vasodilator. Thus, these cardiovascular iatrogenic effects of the chloroquine are important both through their potential frequency and seriousness. Personal clinical cases and medical review enables to identify the main effects, observed either with prophylactic, or curative, or even toxic dosages. The more often, there are some rhythm and conductance disorders, myocardiopathy, even sometimes vasoplegic shocks. A list of the commercial patent medicine including chloroquine enables to be aware, to prevent and to take into account the cardiovascular risks of a treatment newly set or carried on for long years.

Two hundreds mild to moderate hypertensive patients (mean age 54 +/- 10, 115 males, 85 females) were randomised in a multicentre, double blind, two parallel groups trial in order to compare the efficacy of moxonidine (0.2 mg od) and rilmenidine (1 mg od), two selective I1 receptor agonists. The dosage had to be shifted after a four-week treatment period (moxonidine 0.4 mg od or rilmenidine 2 mg bid) if DBP > 90 mmHg. More than half of the patients had to be shifted to a double dose. The blood pressure was normalised (DBP < or = 90 mmHg) for 47% of the moxonidine patient's and 50% of the rilmenidine patients. The DBP decrease reached 7.3 mmHg in the moxonidine group and 8.0 mmHg in the rilmenidine group (P = 0.28). The SBP decrease was the same in the two groups (7.6 mmHg). Both drugs were well tolerated. The great affinity of moxonidine and rilmenidine for the I1 receptors and the weak affinity for the alpha 2 receptors were probably responsible of the small number of adverse events which are generally linked to the centrally acting antihypertensive drugs (asthenia, somnolence, oedema). Because moxonidine and rilmenidine are often to be prescribed at double dose and are often associated with other antihypertensives, moxonidine whose dosage could be shifted without having to increase the number of daily intakes could enhance the patient's comfort and make the compliance easier.

In this study, 9 cases of tachycardia-induced cardiomyopathy have been reported, with a 7-year follow-up period. The patient population consisted of 5 males and 4 females with a mean age of 41 +/- 18 years (range: 10-70 years). It was difficult to determine the onset of the arrhythmia, due to its frequently asymptomatic course until such time as cardiac insufficiency became apparent (this was the case in 7 patients, while 2 subjects had palpitations). Four cases of AV intranodal reentry tachycardia (3 with an accessory pathway), 2 cases of atrial fibrillation, 1 case of auricular flutter, 1 case of atrial tachycardia and 1 case of ventricular tachycardia were observed. Disappearance of the symptomatology following restoration of sinus rhythm was accompanied by echocardiographically-determined normalization of systolic function on average 5 +/- 4 months post-arrhythmia (range: 1-12 months). Left-ventricular end-diastolic volumes decreased from 60 +/- 5 mm to 51 +/- 4 mm (P < 0.01), and end-systolic volumes from 50 +/- 7 mm to 35 +/- 4 mm (P < 0.001), while the left ventricular shortening fraction increased from 17 +/- 5% to 33 +/- 4% (P < 0.0001). In the differential diagnosis for primary dilated cardiomyopathy, tachycardia-induced cardiomyopathy appears very similar to the former, and only an adequate period of follow-up after the restoration of sinus rhythm can confirm the diagnosis.

Left atrial myxoma is considered to be exceptionally rare in the elderly. The authors observed and reported on 19 cases occurring in patients over 75 years of age out of a series of 100 myxomas diagnosed between 1962 and 1997, in 12 women and 7 men (mean age: 80 years, range 75 to 89 years). In 3 cases, the myxomas were chance findings at echocardiography but the 16 symptomatic patients (85%) had left ventricular failure (47%), positional symptoms (25%), pyrexia and poor general health (17%) or systemic embolism (17%). The location of the myxoma was the left atrium in all cases, with mitral valve obstruction in 13 of the 19 cases. Eighteen tumours were attached to the interatrial septum and one to the atrial surface of the anterior mitral leaflet. Calcifications were observed in 5 patients. Surgical ablation of the tumour was performed in 15 of the 19 patients. The post-operative course was usually uncomplicated: one patient died of a cerebral haemorrhage. Four patients did not undergo surgery because of patient refusal in 3 cases and major associated morbidity in the other case. These cases were included in the study because the tumours had all the characteristics of myxomas. Though the discovery of a myxoma remains a classical surgical emergency, the presence of quiescent, non-obstructive, well circumscribed and calcified myxomas with a low risk of obstruction and of embolism in elderly high risk patients may be exceptions to this traditional dogma.

Iatrogenic third degree atrioventricular block due to alpha interferon is rare. The authors present a case which occurred with low dosage, regressed when treatment was withdrawn and reappeared when treatment was reintroduced. The physiopathological mechanism of disease of the conduction pathways and its general cardiotoxicity is not yet understood. The secondary effects of this increasingly widely used anti-tumoral and anti-infectious drug should be recognised in order to prevent them. Initial cardiological investigation and follow-up are indicated to ensure this prevention.

The authors report the cases of two young adults (25 and 27 years) presenting with congenital left ventricular aneurysm or diverticulum with healthy coronary arteries. This saccular evagination of the ventricular wall is rare. The authors describe a classification distinguishing muscular (contractile) diverticula, composed of the three cardiac tunics, fibrous diverticula and finally aneurysms with a dyskinetic wall. Although the limits of this classification are sometimes poorly defined, it presents a prognostic value, because it appears logical to propose nonsurgical management in the context of muscular diverticula and it seems legitimate to operate on fibrous diverticula and aneurysms due to the risks of rupture, extension, thrombosis or arrhythmia.

Background: Atrial fibrillation, the most common sustained cardiac arrhythmia and a major cause of stroke, results from simultaneous reentrant wavelets. Its spontaneous initiation has not been studied., Methods: We studied 45 patients with frequent episodes of atrial fibrillation (mean [+/-SD] duration, 344+/-326 minutes per 24 hours) refractory to drug therapy. The spontaneous initiation of atrial fibrillation was mapped with the use of multielectrode catheters designed to record the earliest electrical activity preceding the onset of atrial fibrillation and associated atrial ectopic beats. The accuracy of the mapping was confirmed by the abrupt disappearance of triggering atrial ectopic beats after ablation with local radio-frequency energy., Results: A single point of origin of atrial ectopic beats was identified in 29 patients, two points of origin were identified in 9 patients, and three or four points of origin were identified in 7 patients, for a total of 69 ectopic foci. Three foci were in the right atrium, 1 in the posterior left atrium, and 65 (94 percent) in the pulmonary veins (31 in the left superior, 17 in the right superior, 11 in the left inferior, and 6 in the right inferior pulmonary vein). The earliest activation was found to have occurred 2 to 4 cm inside the veins, marked by a local depolarization preceding the atrial ectopic beats on the surface electrocardiogram by 106+/-24 msec. Atrial fibrillation was initiated by a sudden burst of rapid depolarizations (340 per minute). A local depolarization could also be recognized during sinus rhythm and abolished by radiofrequency ablation. During a follow-up period of 8+/-6 months after ablation, 28 patients (62 percent) had no recurrence of atrial fibrillation., Conclusions: The pulmonary veins are an important source of ectopic beats, initiating frequent paroxysms of atrial fibrillation. These foci respond to treatment with radio-frequency ablation.