Remodelage cardiaque dans la ville la plus haute du monde‎ : effets de l'altitude et du mal chronique des montagnes

Background: Despite unique adaptations to chronic hypoxic exposure, Andeans highlanders frequently develop a maladaptive syndrome , termed chronic mountain sickness (CMS), characterised by a combination of hypoxaemia, excessive erythrocytosis and various non specific symptoms. The aim of this study was to evaluate cardiac remodelling and pulmonary circulation at rest and during exercise in healthy lowlanders and highlanders and in CMS patients living in the highest city in the world La Rinconada, 5 100 m, Peru). Methods: 98 males were evaluated: 18 healthy lowlanders, 23 healthy highlanders living at 3 800 m, and 55 highlanders living at 5 100 m, among which 17 were asymptomatic (no CMS), 14 reported mild CMS and 24 reported moderate severe CMS. Cardiac remodelling was quantified by rest echocardiography. Pulmonary artery pressure (PAP) and pulmonary vascular resistance (TVR) were measured at rest and during submaximal cycling exercise. Total blood volume and haemoglobin mass were determined using the carbon monoxide rebreathing technique. Result: Heart remodelling, predominantly of the right heart, together with an elevation of resting PAP and an impairment in systolic function progressively occurred with the increase in altitude of residency. The left heart exhibited a progressive concentric remodelling with diastolic dysfunction but without systolic dysfunction. Those modifications were emphasised in moderate severe CMS patients at 5 100 m. Mean PAP was higher both at rest and during exercise in healthy highlanders at 5 100 m albeit without significant difference in TVR. On another hand, the moderate severe CMS subjects had a higher TVR at rest and a larger increase in mPAP during exercise. The right heart remodelling was significantly correlated with resting and exercise m PAP, total blood volume and arterial oxygenation. Conclusions: In the highest city in the world, healthy dwellers exhibit right heart dilatation in response to a chronically increased afterload and a left ventricle concentric remodelling with diastolic dysfunction. Those modifications are accentuated in moderate-severe CMS subjects and may enhance the risk of heart failure.Introduction : Malgré des adaptations uniques à l'hypoxie chronique, les andéens vivant en haute altitude développent fréquemment un syndrome de maladaptation, appelé mal chronique des montagnes (CMS), caractérisé par l'association d'une hypoxémie et de plusieurs symptômes aspécifiques. Le but de cette étude était d'évaluer le remodelage cardiaque et l'hémodynamique pulmonaire au repos et à l'effort chez les habitants de la ville la plus haute du monde (La Rinconada, 5100m, Pérou). Méthodes : 98 sujets ont été évalués : 18 sujets vivant en basse altitude, 23 sujets vivant à 3800m d'altitude et 55 sujets vivant à 5100m d'altitude (17 sans CMS,14 avec un CMS léger, 24 avec un CMS modéré à sévère). Le remodelage cardiaque était quantifié par une échocardiographie. Les pressions artérielles pulmonaires (PAP) et les résistances vasculaires pulmonaires (RVP) étaient mésurées au repos et lors d'un exercice submaximal à vélo. Le volume sanguin total et la masse d'hémoglobine étaient déterminés en utilisant le test de CO rebreathing. Résultats : Un remodelage cardiaque, principalement du coeur droit, associé à une élévation des PAP au repos et à une altération de la fonction systolique se développent progressivement avec l'augmentation de l'altitude de résidence. Le coeur gauche présente un remodelage concentrique progressif avec une dysfonction diastolique, mais sans dysfonction systolique. Ces modifications étaient augmentées chez les sujets souffrant d'un CMS modéré à sévère à 5 100 m. Les PAP moyennes était plus élevées au repos et à l'effort chez les habitants vivant à 5100 m. D'un autre côté, les sujets avec un CMS modéré à sévère avaient des RVP plus élevées au repos et une augmentation plus importante des PAP à l'effort. Le remodelage du ceur droit était significativement corrélé avec les PAP au repos et à l'effort, le volume sanguin total et l'oxygénation artérielle. Conclusions : Dans la ville la plus haute du monde, les habitants présentent une dilatation du ceur droit en réponse à une augmentation chronique de la post-charge et un remodelage concentrique du ventricule gauche avec une dysfonction diastolique. Ces modifications sont accentuées chez les sujets souffrant d'un CMS modéré à sévère, et peuvent augmenter le risque d'insuffisance cardiaque

Letters to Blood: Reevaluation of excessive erythrocytosis in diagnosing chronic mountain sickness in men from the world's highest city

International audienceNo abstract availabl

Cardiac remodelling in the highest city in the world: effects of altitude and chronic mountain sickness

International audienceAbstract Aims A unique Andean population lives in the highest city of the world (La Rinconada, 5100 m, Peru) and frequently develops a maladaptive syndrome, termed chronic mountain sickness (CMS). Both extreme altitude and CMS are a challenge for the cardiovascular system. This study aims to evaluate cardiac remodelling and pulmonary circulation at rest and during exercise in healthy and CMS highlanders. Methods and results Highlanders living permanently at 3800 m (n = 23) and 5100 m (n = 55) with (n = 38) or without CMS (n = 17) were compared with 18 healthy lowlanders. Rest and exercise echocardiography were performed to describe cardiac remodelling, pulmonary artery pressure (PAP), and pulmonary vascular resistance (PVR). Total blood volume (BV) and haemoglobin mass were determined in all people. With the increase in the altitude of residency, the right heart dilated with an impairment in right ventricle systolic function, while the left heart exhibited a progressive concentric remodelling with Grade I diastolic dysfunction but without systolic dysfunction. Those modifications were greater in moderate–severe CMS patients. The mean PAP was higher both at rest and during exercise in healthy highlanders at 5100 m. The moderate–severe CMS subjects had a higher PVR at rest and a larger increase in PAP during exercise. The right heart remodelling was correlated with PAP, total BV, and SpO2. Conclusion Healthy dwellers at 5100 m exhibit both right heart dilatation and left ventricle concentric remodelling with diastolic dysfunction. Those modifications are even more pronounced in moderate–severe CMS subjects and could represent the limit of the heart's adaptability before progression to heart failure

Blood Viscosity and Its Determinants in the Highest City in the World

International audienceKey points: Highlanders develop unique adaptative mechanisms to chronic hypoxic exposure, including substantial haemoglobin and haematocrit increases. However, a significant proportion of populations living permanently at high altitude develop maladaptive features known as chronic mountain sickness (CMS). This study aimed to assess the effects of permanent life at high altitude on clinical and haemorheological parameters (blood viscosity and red blood cell aggregation) and to compare clinical and haemorheological parameters of dwellers from the highest city in the world according to CMS severity. Blood viscosity increased with altitude, together with haemoglobin concentration and haematocrit. At 5100 m, highlanders with moderate-to-severe CMS had higher blood viscosity mainly at high shear rate and even at corrected haematocrit (40%), with a lower red blood cell aggregation. Blood viscosity may contribute to CMS symptomatology but the increased blood viscosity in CMS patients cannot solely be explained by the rise in haematocrit.Abstract: Chronic mountain sickness (CMS) is a condition characterised by excessive erythrocytosis (EE). While EE is thought to increase blood viscosity and subsequently to trigger CMS symptoms, the exact relationship between blood viscosity and CMS symptoms remains incompletely understood. We assessed the effect of living at high altitude on haemoglobin, haematocrit and haemorheological parameters (blood viscosity and red blood cell aggregation), and investigated their relationship with CMS in highlanders living in the highest city in the world (La Rinconada, Peru, 5100 m). Ninety-three men participated in this study: 10 Caucasian lowlanders, 13 Andean highlanders living at 3800 m and 70 Andean highlanders living at 5100 m (35 asymptomatic, CMS score ≤5; 15 with mild CMS, CMS score between 6 and 10; 20 with moderate-to-severe CMS, CMS score >10). Blood viscosity was measured at native and corrected haematocrit (40%). Haemoglobin concentration and haematocrit increased with the altitude of residency. Blood viscosity also increased with altitude (at 45 s-1 : 6.7 ± 0.9 mPa s at sea level, 14.0 ± 2.0 mPa s at 3800 m and 27.1 ± 8.8 mPa s at 5100 m; P < 0.001). At 5100 m, blood viscosity at corrected haematocrit was higher in highlanders with moderate-to-severe CMS (at 45 s-1 : 18.9 ± 10.7 mPa s) than in highlanders without CMS (10.2 ± 5.9 mPa s) or with mild CMS (12.1 ± 6.1 mPa s) (P < 0.05). In conclusion, blood viscosity may contribute to CMS symptomatology but the increased blood viscosity in CMS patients cannot solely be explained by the rise in haematocrit

Nocturnal hypoxemia, blood pressure, vascular status and chronic mountain sickness in the highest city in the world

International audienceIntroduction: Chronic mountain sickness (CMS) is a condition characterized by excessive erythrocytosis in response to chronic hypobaric hypoxia. CMS frequently triggers cardiorespiratory diseases such as pulmonary hypertension and right or left heart failure. Ambient hypoxia might be further amplified night-time by intermittent hypoxia related to sleep-disordered breathing (SDB) so that sleep disturbance may be an important feature of CMS. Our aim was to characterize in a cross-sectional study nocturnal hypoxaemia, SDB, blood pressure (BP), arterial stiffness and carotid intima-media thickness (CIMT) in highlanders living at extreme altitude. Methods: Men aged 18 to 55 years were prospectively recruited. Home sleep apnoea test, questionnaires (short-form health survey; Montreal cognitive assessment; Pittsburgh Sleep Questionnaire Index and the Insomnia severity index), 24-h ambulatory BP monitoring, CIMT and arterial stiffness were evaluated in 3 groups: i) Andean lowlanders (sea-level); ii) highlanders living at 3,800 m and iii) highlanders living at 5,100 m. Analyses were conducted in subgroups according to 1) CMS severity 2) healthy subjects living at the three different altitude. Results: Ninety-two males were evaluated at their living altitudes. Among the 54 highlanders living at 5,100 m, subjects with CMS showed lower mean nocturnal oxygen saturation (SpO 2), SpO 2 nadir, lower pulse wave velocity and higher nocturnal BP variability than those with no-CMS. Lower nocturnal SpO 2 nadir was associated with higher CMS severity (ß¼ À0.14, p¼.009). Among the 55 healthy subjects, healthy highlanders at 5,100 m were characterized by lower scores on quality of life and sleep quality scales and lower mean SpO 2 compared to lowlanders. Conclusions: Lower nocturnal SpO 2 and higher nocturnal BP variability are associated with CMS severity in individuals living permanently at high altitude. The role of lower SpO 2 and higher nocturnal BP variability in the cardiovascular progression of CMS and in the overall prognosis of the disease need to be evaluated in further studies

Nocturnal hypoxemia, blood pressure, vascular status and chronic mountain sickness in the highest city in the world

Introduction: Chronic mountain sickness (CMS) is a condition characterized by excessive erythrocytosis in response to chronic hypobaric hypoxia. CMS frequently triggers cardiorespiratory diseases such as pulmonary hypertension and right or left heart failure. Ambient hypoxia might be further amplified night-time by intermittent hypoxia related to sleep-disordered breathing (SDB) so that sleep disturbance may be an important feature of CMS. Our aim was to characterize in a cross-sectional study nocturnal hypoxaemia, SDB, blood pressure (BP), arterial stiffness and carotid intima-media thickness (CIMT) in highlanders living at extreme altitude. Methods: Men aged 18 to 55 years were prospectively recruited. Home sleep apnoea test, questionnaires (short-form health survey; Montreal cognitive assessment; Pittsburgh Sleep Questionnaire Index and the Insomnia severity index), 24-h ambulatory BP monitoring, CIMT and arterial stiffness were evaluated in 3 groups: i) Andean lowlanders (sea-level); ii) highlanders living at 3,800 m and iii) highlanders living at 5,100 m. Analyses were conducted in sub-groups according to 1) CMS severity 2) healthy subjects living at the three different altitude. Results: Ninety-two males were evaluated at their living altitudes. Among the 54 highlanders living at 5,100 m, subjects with CMS showed lower mean nocturnal oxygen saturation (SpO2), SpO2 nadir, lower pulse wave velocity and higher nocturnal BP variability than those with no-CMS. Lower nocturnal SpO2 nadir was associated with higher CMS severity (ß= −0.14, p=.009). Among the 55 healthy subjects, healthy highlanders at 5,100 m were characterized by lower scores on quality of life and sleep quality scales and lower mean SpO2 compared to lowlanders. Conclusions: Lower nocturnal SpO2 and higher nocturnal BP variability are associated with CMS severity in individuals living permanently at high altitude. The role of lower SpO2 and higher nocturnal BP variability in the cardiovascular progression of CMS and in the overall prognosis of the disease need to be evaluated in further studies

Impact of High-Dose Prophylactic Anticoagulation in Critically Ill Patients With COVID-19 Pneumonia

International audienceBACKGROUND: Because of the high risk of thrombotic complications (TCs) during SARS-CoV-2 infection, several scientific societies have proposed to increase the dose of preventive anticoagulation, although arguments in favor of this strategy are inconsistent. RESEARCH QUESTION: What is the incidence of TC in critically ill patients with COVID-19 and what is the relationship between the dose of anticoagulant therapy and the incidence of TC? STUDY DESIGN AND METHODS: All consecutive patients referred to eight French ICUs for COVID-19 were included in this observational study. Clinical and laboratory data were collected from ICU admission to day 14, including anticoagulation status and thrombotic and hemorrhagic events. The effect of high-dose prophylactic anticoagulation (either at intermediate or equivalent to therapeutic dose), defined using a standardized protocol of classification, was assessed using a time-varying exposure model using inverse probability of treatment weight. RESULTS: Of 538 patients included, 104 patients experienced a total of 122 TCs with an incidence of 22.7% (95% CI, 19.2%-26.3%). Pulmonary embolism accounted for 52% of the recorded TCs. High-dose prophylactic anticoagulation was associated with a significant reduced risk of TC (hazard ratio, 0.81; 95% CI, 0.66-0.99) without increasing the risk of bleeding (HR, 1.11; 95% CI, 0.70-1.75). INTERPRETATION: High-dose prophylactic anticoagulation is associated with a reduction in thrombotic complications in critically ill patients with COVID-19 without an increased risk of hemorrhage. Randomized controlled trials comparing prophylaxis with higher doses of anticoagulants are needed to confirm these results