No description available.

Pulse wave velocity (PWV) and augmentation index (AI) are independent predictors of cardiovascular health. However, the comparability of multiple oscillometric modalities currently available for their assessment was not studied in detail. In the present study, we aimed to evaluate the relationship between indices of arterial stiffness assessed by diastolic and suprasystolic oscillometry. In total, 56 volunteers from the general population (23 males; median age 70 years [interquartile range: 65–72 years]) were recruited into observational feasibility study to evaluate the carotid-femoral/aortic PWV (cf/aoPWV), brachial-ankle PWV (baPWV), and AI assessed by 2 devices: Vicorder (VI) applying diastolic, right-sided oscillometry for the determination of all 3 indices, and Vascular explorer (VE) implementing single-point, suprasystolic brachial oscillometry (SSBO) pulse wave analysis for the assessment of cfPWV and AI. Within- and between-device correlations of measured parameters were analyzed. Furthermore, agreement of repeated measurements, intra- and inter-observer concordances were determined and compared for both devices. In VI, both baPWVand cfPWVinter-correlatedwell and showed good level of agreement with bilateral baPWVmeasured byVE (baPWV[VI]– baPWV[VE]R: overall concordance correlation coefficient [OCCC]¼0.484, mean difference¼1.94 m/s; cfPWV[VI]–baPWV[- VE]R: OCCC¼0.493, mean difference¼1.0m/s). In contrast, SSBO derived aortic PWA (cf/aoPWA[VE]) displayed only weak correlation with cfPWV(VI) (r¼0.196; P¼0.04) and ipsilateral baPWV (cf/ aoPWV[VE]R–baPWV[VE]R: r¼0.166; P¼0.08). cf/aoPWA(VE) correlated strongly with AI(VE) (right-sided: r¼0.725, P<0.001). AI exhibited marginal between-device agreement (right-sided: OCCC¼ 0.298, mean difference: 6.12%). All considered parameters showed good-to-excellent repeatability giving OCCC > 0.9 for 2-point-PWV modes and right-sided AI(VE). Intra- and inter-observer concordances were similarly high except for AI yielding a trend toward better reproducibility in VE (interobserver–OCCC[VI] vs [VE]¼0.774 vs 0.844; intraobserver OCCC[VI] vs [VE]¼0.613 vs 0.769). Both diastolic oscillometry-derived PWV modes, and AI measured either with VI or VE, are comparable and reliable alternatives for the assessment of arterial stiffness. Aortic PWV assessed by SSBO in VE is not related to the corresponding indices determined by traditional diastolic oscillometry.

La dysfonction diastolique du ventricule gauche (DDVG) réfère à une rigidité ainsi qu’à des troubles de relaxation au niveau de ce ventricule pendant la phase de la diastole. Nos connaissances sur les mécanismes moléculaires sous-jacents de cette pathologie demeurent limités. Les analyses géniques sont indispensables afin de bien identifier les voies par lesquelles cette maladie progresse. Plusieurs techniques de quantification de l’expression génique sont disponibles, par contre la RT-qPCR demeure la méthode la plus populaire vu sa haute sensibilité et de ses coûts modérés. Puisque la normalisation occupe un aspect très important dans les expériences de RT-qPCR, nous avons décidé de sélectionner des gènes montrant une haute stabilité d’expression dans un modèle de DDVG de lapin. Nous avons alors exposé 18 lapins blancs soit à une diète normale (n=7) ou bien à une diète hypercholestérolémiante additionnée de vitamine D2 (n=11). La DDVG a été évaluée par des mesures échocardiographiques. L’expression de l’ARNm de dix gènes communément utilisés dans la littérature comme normalisateur (Gapdh, Hprt1, Ppia, Sdha, Rpl5, Actb, Eef1e1, Ywhaz, Pgk1, et G6pd) a été mesurée par RT-qPCR. L’évaluation de leur stabilité a été vérifiée par les algorithmes de geNorm et Normfinder. Sdha et Gapdh ont obtenu les meilleurs scores de stabilité (M<0.2) et ont été suggérés par le geNorm, comme meilleure combinaison. Par contre, l’utilisation de Normfinder mène à la sélection d’Hprt1 et Rpl5 comme meilleure combinaison de gènes de normalisation (0.042). En normalisant par ces deux combinaisons de gènes, l’expression de l’ARNm des peptides natriurétiques de type A et B (Anp et Bnp), de la protéine chimiotactique des monocytes-1 (Mcp-1) et de la sous unité Nox-2 de la NADPH oxydase ont montré des augmentations similaires chez le groupe hypercholestérolémique comparé au groupe contrôle (p<0.05). Cette augmentation d’expressions a été corrélée avec plusieurs paramètres échocardiographiques de DDVG. À notre connaissance, c’est la première étude par laquelle une sélection de gènes de référence a été réalisée dans un modèle de lapin développant une DDVG. / Left ventricular diastolic dysfunction (LVDD) is characterized by the diminution of ventricle’s performance, its incapacity to relax normally and an increase of blood filling pressure. LVDD is considered as a main cause of heart failure in approximately 50% of patients suffering from this disease. However, the molecular mechanisms underlying LVDD remain unclear. Real-time quantitative PCR (RT-qPCR) is widely used in gene-expression studies. In this study we attempt to establish normalization genes for gene expression analysis in a rabbit model of LVDD. Eighteen New-Zealand white rabbits were exposed to normal (n=7) or 0.5% hypercholesterolemic (n=11) diet supplied by vitamin D2; an LVDD animal model previously characterized in our Laboratory. LVDD was assessed by echocardiography. RT-qPCR was performed using cDNA from left ventricle samples and measuring the stability of 10 candidate genes as normalisers (Gapdh, Hprt1, Ppia, Sdha, Rpl5, Actb, Eef1e1, Ywhaz, Pgk1, and G6pd). We found that Sdha and Gapdh are the most stable genes using geNorm analysis with very high stability average M <0.2. By contrast, Hprt1 and Rpl5 were found to be the best combination for normalization with a stability value of 0.042 when using Normfinder. Comparison of both normalization strategies highlighted an increase of Anp, Bnp, Mcp-1 and Nox-2 mRNA expression in the hypercholesterolemic rabbits (p<0.05) compared to normal controls. This increase correlates with different DD parameters and validates the development of the disease in our model. To our knowledge, this is the first study highlighting stable reference genes for RT-qPCR normalization in a validated rabbit model of LVDD.

No description available.

Background The prevalence and incidence of stroke are known to increase with age, which, combined with demographic change, means that very old patients with stroke are a growing patient group. Risk factors for incident stroke among very old people have not been widely investigated. The impact of depression on mortality in very old people who have had a stroke also remains unclear.  The aim of this thesis was to investigate the risk factors for incident stroke, the epidemiology of stroke and depression, and the consequences of having had a stroke regarding the risk of depression and mortality among very old people. Methods A randomly selected half of 85-, all 90-, and all ≥95-year-olds in certain municipalities in Västerbotten County, Sweden, and Pohjanmaa County, Finland were targeted in a population-based cohort study from 2000-2012. The 65-, 70-, 75-, and 80-year-olds in all the rural and random samples from the urban municipalities in the same counties were furthermore targeted in a survey in 2010. In the cohort study patients were assessed in their homes, by means of the 15-item Geriatric Depression Scale (GDS-15) and other assessment scales, as well as blood pressure measurements, several physical tests, and a review of medical diagnoses appearing in the medical charts. Incident stroke data were collected from medical charts guided by hospital registry records, cause of death records, and reassessments after 5 years. Depression was defined as a GDS-15 score ≥5. A clinical definition of all depressive disorders, based on assessment scale scores and review of medical charts was also used. A specialist in geriatric medicine evaluated the diagnoses. The survey included yes/no questions about stroke and depression status, and the 4-item Geriatric Depression Scale. Associations with mortality and incident stroke were tested using Cox proportional-hazard models.  Results In the ≥85-year-olds examined in 2005-2007 (n=601), the stroke prevalence was 21.5%, the prevalence of all depressive disorders was 37.8% and stroke was independently associated with depressive disorders (odds ratio 1.644, p=0.038). The prevalence of depression according to GDS-15 scores was 43.2% in people with stroke compared with 25.0% in people without stroke (p=0.001). However, in ≥85-year-olds examined in Sweden from 2000-2012 (n=955), from all past data collections in the study, depression was not independently associated with incident stroke.  In ≥65-year-olds who responded to a survey in 2010 (n=6098), the stroke prevalence rose with age from 4.7% among the 65- to 11.6% among the 80-year-olds (p&lt;0.001). The prevalence of depression rose from 11.0% among the 65- to 18.1% among the 80-year-olds (p&lt;0.001). In the group with stroke, depression was independently associated with dependence in personal activities of daily living and having a life crisis the preceding year, while in the non-stroke group, depression was independently associated with several additional demographic, social and health factors. In ≥85-year-olds examined in 2005-2007 with valid GDS-15 tests (n=452), having had a stroke was associated with increased 5-year mortality [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.15-2.03]. Having had a stroke and depression was associated with increased 5-year mortality compared with having only stroke (HR 1.90, 95% CI 1.15-3.13), having only depression (HR 1.59, 95% CI 1.03-2.45), and compared with having neither stroke nor depression (HR 2.50, 95% CI 1.69-3.69). Having only stroke without a depression did not increase mortality compared with having neither stroke nor depression. In ≥85-year-olds examined in Sweden from 2000-2012 (n=955), from all past data collections in the study, the stroke incidence was 33.8/1000 person-years during a mean follow-up period of about three years. In a comprehensive multivariate model, atrial fibrillation (HR 1.85, 95% CI 1.07–3.19) and higher systolic blood pressure (SBP; HR 1.19, 95% CI 1.08–1.30 per 10-mmHg increase) were associated with incident stroke overall. In additional multivariate models, diastolic blood pressure (DBP) ≥90 mmHg (HR 2.45, 95% CI 1.47–4.08) and SBP ≥160 mmHg (v. &lt;140 mmHg; HR 2.80, 95% CI 1.53–5.14) were associated with incident stroke. Conclusion The prevalence of both stroke and depression increased with age, and rates were especially high among very old people. Having had a stroke was independently associated with a higher prevalence of depression among very old people, however, depression was not independently associated with a higher incidence of stroke. Having had a stroke was associated with increased all-cause mortality among very old people, but only among those who were also depressed. High SBP (≥160 mmHg), DBP (≥90 mmHg) and atrial fibrillation were the only consistent independent risk factors for incident stroke among very old people. / I västvärlden inklusive Sverige så ökar gruppen av människor som uppnår åldern 80 år eller äldre. Människorna som uppnår denna mycket höga ålder har en hög förekomst av kardiovaskulära riskfaktorer, har ofta flera samtidiga sjukdomar och ofta funktionsnedsättningar. Medicinska behandlingsåtgärder är ofta mindre effektiva och förknippade med biverkningar i åldersgruppen. Stroke är en sjukdom som beror på skada av hjärnvävnad till följd av minskad blodtillhörsel till delar av hjärnan. Det är känt att såväl förekomsten av och insjuknandet i stroke ökar med stigande ålder. Den som drabbas av stroke löper risk att få en bestående funktionsnedsättning och att dö i förtid. En vanlig komplikation efter att ha drabbats av stroke är nedstämdhet eller depression. Vetenskapliga studier om stroke har tidigare negligerat mycket gamla människor, vilket i takt med den pågående demografiska utvecklingen framstått som allt mer orimligt. Det är ej helt klarlagt vilka riskfaktorer som leder till att insjukna med stroke i mycket hög ålder. Överdödligheten förknippad med att drabbas av depression efter stroke är också oklar i åldersgruppen. Det är också oklart vad som skiljer depression efter stroke från depression bland den övriga befolkningen av åldrade människor. Den populations-baserade kohortstudien GErontologisk Regional DAtabas (GERDA) inleddes år 2000 för att kartlägga faktorer förknippade med gott åldrande bland mycket gamla människor. Hälften av 85-åringarna, alla 90-åringar och alla ≥95-åringar i utvalda kommuner i Västerbotten erbjöds att delta i studien. Därefter har återbesök hos tidigare deltagare i sina nya åldersgrupper och rekrytering av nya deltagare genomförts vart femte år. Studien utvidgades med utvalda kommuner i Österbotten, Finland vid den första femårsuppföljningen. Datainsamlingen i studien bestod av demografiska frågor, skattningsskalor, blodtrycksmätning och kognitiva test genomförda vid ett hembesök i deltagarens hem, samt genomgång av journalhandlingar. År 2010 skickades även en enkät ut till 65-, 70-, 75- och 80-åringar i alla kommuner i Västerbotten och Österbotten. Enkäten innehöll frågor om demografi, hälsa, sjukdomar och intressen. Bland deltagarna i kohortstudien bestämdes förekomsten av tidigare stroke baserat på genomgång av journaluppgifter och uppgifter från hembesöken. Förekomsten av depression bestämdes baserat på poängsättning från en validerad skattningsskala för depression, samt baserat på en sammanvägning av journaluppgifter och skattningsskalor. En specialist i geriatrik fattade det slutliga beslutet om diagnoser. Insjuknande i stroke bestämdes baserat på journalgenomgång av individer med stroke-relaterade diagnoskoder i sjukhusregistret, i dödsorsaksregistret eller uppgift om stroke vid femårsuppföljningen i studien. Bland deltagarna i enkätstudien bestämdes förekomsten av tidigare stroke baserat på självrapportering, och förekomsten av depression bestämdes baserat på en sammanvägning av självrapportering och en skattningsskala för depression.  Förekomsten av stroke i enkätstudien steg med ålder, från 4.7% bland 65-åringar till 11.6% bland 80-åringar. Förekomsten av stroke var omkring 20% bland ≥85-åringar, med minimal variation mellan 85-, 90- och ≥95-åringar. Förekomsten av depression var högre bland dem med stroke jämfört med de övriga deltagarna, både gällande den sammavägda diagnosen och baserat endast på poängsättning. Stroke och sömnproblem var oberoende associerade med depression. Bland ≥65-åringar i enkätstudien var funktionsnedsättning och genomgången livskris associerade med depression hos dem med en tidigare stroke. Bland deltagare utan stroke var ett antal ytterligare externa faktorer, inklusive subjektiv upplevelse av dålig ekonomi och att inte ha någon att anförtro sig till, associerade med depression. Både stroke och depression var associerade med ökad dödlighet bland ≥85-åringar. De med stroke utan depression hade en dödlighet i linje med normalbefolkningen utan stroke eller depression. Förekomsten av samtidig stroke och depression var associerad med högre dödlighet än normalbefolkningen, jämfört med dem med enbart stroke eller enbart depression. Högt systoliskt blodtryck (≥160 mmHg), högt diastoliskt blodtryck (≥90 mmHg) och förmaksflimmer var oberoende riskfaktorer för att insjukna i stroke bland ≥85-åringarna. Sambandet mellan blodtryck och strokerisk försvagades ej hos människor med kognitiv eller funktionell nedsättning. Tidigare stroke, hjärtsvikt, kognitiv nedsättning, näringsbrist, depressiva symtom och låg gånghastighet var också associerade med att insjukna i stroke, men ej oberoende av varandra. Sammanfattningsvis så stiger förekomsten av stroke med åldern och är särskilt hög bland mycket gamla människor. Depression är betydligt vanligare hos mycket gamla människor med stroke, även justerat för störningsfaktorer. Depression är främst associerat med funktions-nedsättning hos människor med stroke, men med ett större antal externa faktorer hos människor utan stroke. Mycket gamla människor med stroke har särskilt hög dödlighet om de samtidigt är deprimerade, men en dödlighet i linje med normalbefolkningen om de inte är deprimerade. Högt systoliskt och diastoliskt blodtryck samt förmaksflimmer är viktiga och behandlingsbara orsaker till att drabbas av stroke i mycket hög ålder.

Les auto-tensiomètres (AT) sont parmi les dispositifs les plus utilisés en clinique et à domicile pour la mesure de la pression artérielle (PA). Ces appareils utilisent deux algorithmes heuristiques (Height-Based/HB et Slope-Based/SB) pour déterminer les pressions artérielles systoliques (PAS) et diastoliques (PAD) à partir de l'enregistrement de la pression oscillométrique dans le brassard. La mise sur le marché de ces appareils est actuellement assujettie à la directive 93/42/CE, qui nécessite une étude clinique basée sur une comparaison avec des mesures de la PA par auscultation. Cette méthode, qui consiste à détecter des sons de Korotkoff dans l'artère auscultée, présente l'inconvénient d'être praticien dépendante et engendre une incertitude sur la mesure de la PAS et de la PAD. Il est donc nécessaire de s'assurer de la fiabilité de ces instruments en proposant un dispositif expérimental de référence permettant en outre de pallier l'étude clinique qui s'avère longue et coûteuse. Cette thèse est dédiée à la mise en place de ce dispositif ou chaîne de référence, qui associe un banc d'essai permettant la validation des auto-tensiomètres et une base de données de mesure de PA. Afin de réaliser notre objectif, une étude clinique a été réalisée à l'hôpital Nord de Marseille à l'issue d'un examen de coronarographie. L'étude, réalisée sur 115 patients, compare des mesures de pression invasives (mesures de référence) à des mesures de pression non-invasives : des mesures auscultatoires, des mesures via un auto-tensiomètre commercial et des mesures oscillométriques. Ces dernières ont été réalisées concomitamment avec la PA invasive. / Automated blood pressure (ABP) devices are among the most commonly used devices for diagnosis arterial blood pressure (BP) for clinical and home use. These devices use two heuristic algorithms (Height-Based/HB and Slope-Based/SB) to determine the systolic blood pressure (SBP) and the diastolic blood pressure (DBP) from the recording of an oscillometric pressure signal collected using an inflatable cuff. Currently ABP are in the scope of Directive 93/42/CE, which requires a clinical study based on a comparison of BP measurements using auscultatory method. Unfortunately auscultatory measurements have the disadvantage of the uncertainties related to perception of Korotkoff sounds, leading to an uncertainty of measuring SBP and DBP. Therefore it is necessary to ensure the reliability of these instruments and to propose an experimental reference chain to validate ABP devices without returning to expensive and long clinical campaign. The purpose of this thesis is to create and develop a calibration chain for measuring arterial BP, which is composed of database of arterial BP measurements and a patient simulator for regenerating oscillometric measurements. To achieve our target, a clinical study was conducted at the northern hospital of Marseille (l'hôpital Nord) after a coronary exam. The clinical study of 115 patients compares invasive blood pressure measurements (reference measurements) and non-invasive blood pressure measurements: auscultatory measurements, measurements using a commercial automated blood pressure device and oscillometric measurements. The latter were carried out simultaneously with the invasive BP measurements.

On estime qu'approximativement 20 millions de personnes dans le monde souffrent d'insuffisance cardiaque et la prévalence de cette pathologie ne cesse d'augmenter avec le vieillissement croissant de la population. L'évaluation de la fonction ventriculaire gauche par la mesure de la fraction d'éjection permet en fait de distinguer deux populations distinctes de patients insuffisants cardiaques : l'une avec et l'autre sans altération de la fraction d'éjection, encore dénommées respectivement Heart Failure with Reduced Ejection Fraction (IC-FEr) et Heart Failure with Preserved Ejection Fraction (IC-FEp). On ne sait pas aujourd'hui si ces deux entités représentent deux pathologies distinctes ou, au contraire, deux entités intimement liées. L'IC-FEp est actuellement observée chez environ 40 à 50% des patients présentant une insuffisance cardiaque et son évolution est semblable à celle des patients IC-FEr.Le concept d'IC-FEp soulève toutefois des difficultés conceptuelles : d'une part car la notion d'une fraction d'éjection préservée implique la connaissance de sa valeur de base et d'autre part, les valeurs dites "normales" de la fraction d'éjection sont encore à établir. Par ailleurs, la vision mécanique du cœur comme une pompe hémodynamique ou musculaire conditionne la compréhension de la physiopathologie de la IF-FEp.Dans ce contexte, nous avons mis au point un modèle porcin de dysfonction diastolique avec éjection préservée secondaire à une hypertension artérielle induite par une perfusion continue d'angiotensine II pendant 28 jours. Dans ces conditions, nous avons démontré une altération de la fonction ventriculaire gauche alors même que l'éjection était préservée. Ceci était objectivé par 1) une augmentation paradoxale des durées relatives de contraction et de relaxation isovolumiques, 2) des réponses inappropriées des phases isovolumiques du cycle cardiaque à des augmentations de la fréquence et de l'inotropisme cardiaques et 3) une étroite relation entre ces deux phases isovolumiques (couplage contraction-relaxation). L'inadéquation entre les niveaux de fréquence cardiaque et des phases isovolumiques nous a amené à évaluer les effets de la modulation pharmacologique de la fréquence cardiaque sur le couplage contraction-relaxation. Ainsi la réduction sélective de la fréquence cardiaque par l'administration d'ivabradine, un inhibiteur des canaux If, a réduit significativement la durée de ces deux phases et favorisé le remplissage. Cependant, cette normalisation n'était qu'apparente puisque le ratio entre la contraction et la relaxation isovolumiques restait augmenté à J28, en défaveur de la contraction isovolumique.En conclusion, le développement d'une dysfonction diastolique avec une éjection préservée s'accompagne d'une dysfonction systolique qui entrave une réponse adéquate du myocarde à un stress dans un contexte d'hypertension chronique. / Approximately 20 millions individuals in the world experience heart failure symptoms; heart failure prevalence is continuously rising with population aging. Left ventricular function evaluation by the ejection fraction allows distinguishing two different patient sets: one with and one other without ejection fraction alteration, respectively named Heart Failure with Reduced Ejection Fraction (HF-rEF) and Heart Failure with Preserved Ejection Fraction (HF-pEF). It is unknown if these two clinical presentations represent two different pathologies or two manifestations of the same clinical entity. HF-pEF is found in about 40-50% of patients with heart failure and its evolution is similar to that of patients with HF-rEF.However, several conceptual difficulties deal with the HFpEF: on one hand, talking about preserved ejection fraction implies the knowledge of its basal value; on the other, the normality needs to be established. Moreover, considering the heart either as a hemodynamic pump or as a muscular pump may modify the understanding of HFpEF physiopathology.We therefore set up a swine model of diastolic dysfunction with preserved ejection induced by chronic hypertension, which was obtained by continuous perfusion of angiotensin II during 28 days. In these conditions, we clearly demonstrated a LV function impairment, while the ejection phase parameters remained preserved. The LV impairment is demonstrated by: 1) the paradox increase of the relative durations of isovolumic contraction and relaxation; 2) the blunted responses of the isovolumic phases of cardiac cycle to heart rate augmentation and cardiac inotropisme; 3) a straight relationship between these two isovolumic phases (contraction-relaxation relationship).The mismatch between the heart rate and the isovolumic phases behaviour led us to investigate the possible effects of the heart rate pharmacological modulation on the contraction-relaxation coupling. The selective reduction of the heart rate by ivabradine administration (a selective If channel inhibitor) was able to significantly reduce the isovolumic contraction and relaxation phases' durations, thus improving filling phase dynamics. Anyway, this “normalisation” was only apparent, because the contraction to relaxation ratio was increased at day 28, to the detriment of the isovolumic contraction.In conclusion, chronic hypertension induces a diastolic dysfunction with a preserved ejection fraction paralleled by a systolic dysfunction which is responsible of a blunted myocardial response to stress.

INTRODUÇÃO: Endomiocardiofibrose (EMF) é uma cardiomiopatia restritiva (CMR), caracterizada por uma disfunção diastólica, mas com a função sistólica e a fração de ejeção preservadas ou, em fases avançadas da doença, pouco prejudicadas. O consumo máximo de oxigênio (VO2) é um marcador de mortalidade na insuficiência cardíaca sistólica (ICS). Apesar da mortalidade ser semelhante entre a CMR e ICS, ainda não é conhecido se o treinamento físico pode melhorar o VO2 pico em pacientes com EMF. O objetivo deste estudo foi verificar se 4 meses de treinamento combinado podem melhorar a capacidade funcional e qualidade de vida em pacientes com EMF. MÉTODOS: Vinte e um pacientes com EMF (classe funcional II e III, NYHA) foram divididos em 2 grupos: treinamento físico (EMF-TF, n = 9) e sedentários (EMF-Sed, n = 12). Foram avaliados: VO2 pico, pulso de O2, relação deltaFC/deltaVO2 e relação deltaVO2/deltaW, pelo teste cardiopulmonar (TECP); volume diastólico final (VDF), volume sistólico (VS) e volume diastólico do átrio esquerdo (AE), pela ecocardiografia (Simpson); e qualidade de vida, pelo questionário Minnesota Living With Heart Failure Questionnaire (MLWHFQ). Os resultados do TECP dos pacientes com EMF foram comparados com os resultados de indivíduos controle saudáveis sedentários (CSS). Foi considerado significativo P < 0,05. RESULTADOS: Idade não foi diferente entre EMF-Sed, EMF-TF e CSS (58±9 vs. 55±8 vs. 53±6 anos, P = 0,31; respectivamente). O grupo EMF-TF apresentou um aumento do VO2 pico pós-intervenção, comparado com o momento pré e comparado com o grupo EMF-Sed, mas esse valor foi menor, comparado ao CSS (17,4 ± 3,0 para 19,7 ± 4,4 vs. 15,3 ± 3,0 para 15,0±2.0 vs. 24,5 ± 4,6 ml/kg/min, P < 0,001; respectivamente). O pulso de O2 do grupo EMF-TF no momento pós-intervenção foi maior, comparado ao momento pré e ao grupo EMF-Sed, mas foi semelhante, quando comparado ao grupo CSS (9,3 ± 2,6 para 11,1 ± 2,8 vs. 8,6 ± 2,2 para 8,6 ± 1 vs. 11,2 ± 2,9 ml/batimentos; P < 0,05; respectivamente). A relação deltaFC/deltaVO2 diminuiu no momento pós-intervenção no grupo EMF-TF, comparado ao momento pré e ao grupo EMF-Sed, igualando-se ao grupo CSS (75 ± 36 para 57 ± 14 vs. 68 ± 18 para 73 ± 14 vs. 56±17 bpm/L; P < 0,05; respectivamente). O grupo EMF-TF reduziu significativamente a relação deltaVO2/deltaW, após o período de treinemento, comparado ao momento pré e ao grupo EMF-Sed, igualando-se ao grupo CSS (12,3 ± 2.8 para 10,2 ± 1.9 vs. 12,6±1.7 para 12,4 ± 1.7 vs. 10,0 ± 0,9 ml/min/Watts; P = 0,002; respectivamente). O treinamento físico também aumentou o VDF do grupo EMF-TF, quando comparado ao grupo EMF-Sed (102,1 ± 64,6 para 136,2 ± 75,8 vs. 114,4 ± 55,0 para 100,4 ± 49,9 ml; P < 0,001; respectivamente) e o VS (57,5±31,9 para 72,2 ± 27,4 vs. 60,1 ± 25,2 para 52,1 ± 18,1 ml; P = 0,01; respectivamente), e diminuiu o volume diastólico do AE [69,0 (33,3- 92,7) para 34,9 (41,1-60,9) vs. 44,6 (35,8-73,3) para 45,6 (27,0-61,7) ml; P < 0,001; respectivamente). A qualidade de vida dos pacientes EMF-TF, quando comparados com o grupo EMF-Sed também melhorou após o período de treinamento físico (45±17 para 27±15 vs. 47±20 para 45 ± 23 pontos; P < 0,05; respectivamente). CONCLUSÃO: Esses resultados esclarecem que os pacientes com EMF se beneficiaram com o treinamento físico combinado, enfatizando a importância dessa ferramenta não farmacológica no tratamento clínico habitual desses pacientes / BACKGROUND: Endomyocardial fibrosis (EMF) is a restrictive cardiomyopathy (RCM), characterized by a diastolic dysfunction, but with preserved systolic function and preserved ejection fraction, except in severe cases, in which these two present mild reduction. Maximal oxygen consumption (VO2) is a marker of mortality in systolic heart failure (SHF). Although mortality in RCM can be similar to SHF, it is still unknown if physical training can improve peak VO2 in patients with EMF. The aim of the present study was to evaluate if 4 months of combined physical training could improve functional capacity and quality of life in patients with EMF. METHODS: Twenty one EMF patients (functional class II and III, NYHA) were divided into 2 groups: physical training (EMF-PT, n = 9) and sedentary (EMF-Sed, n = 12). Peak VO2, O2 pulse, deltaFC/deltaVO2 relation and deltaVO2/deltaW relation were evaluated by cardiopulmonary exercise test (CPX); end diastolic volume (EDV), stroke volume (SV) and left atrium diastolic volume were evaluated by echocardiography (Simpson); and quality of life was evaluated by Minnesota Living With Heart Failure Questionnaire (MLWHFQ). CPX results from EMF patients were compared to a healthy sedentary (HS) control group. Significance was considered P < 0,05. RESULTS: Age was not different between EMF-PT, EMF-Sed and HS (58 ± 9 vs. 55±8 vs. 53 ± 6 years, P = 0,31; respectively). EMF-PT group presented an increase in peak VO2 after training compared to EMF-Sed group, but was lower compared to HS (17,4 ± 3,0 to 19,7 ± 4,4 vs. 15,3 ± 3,0 to 15,0 ± 2.0 vs. 24,5 ± 4,6 ml/kg/min, P < 0,001; respectively). O2 pulse in EMF-PT group increased after training compared to EMFSed group, and was similar compared to HS (9,3 ± 2,6 to 11,1±2,8 vs. 8,6±2,2 to 8,6 ± 1 vs. 11,2±2,9 ml/betas; P < 0,05; respectively). deltaFC/deltaVO2 relation decreased after training in EMF-PT group compared to EMF-Sed group, and was similar compared to HS (75 ± 36 to 57 ± 14 vs. 68 ± 18 to 73 ± 14 vs. 56 ± 17 bpm/L; P < 0,05; respectively). deltaVO2/deltaW relation decreased after training in EMF-PT group compared to EMF-Sed group, and was similar compared to HS (12,3 ± 2.8 to 10,2 ± 1.9 vs. 12,6 ± 1.7 to 12,4 ± 1.7 vs. 10,0 ± 0,9 ml/min/Watts; P = 0,002; respectively). Physical training also increased EDV in EMF-PT compared to EMFSed (102,1±64,6 to 136,2±75,8 vs. 114,4±55,0 to 100,4±49,9 ml; P < 0,001; respectively) and SV (57,5±31,9 to 72,2±27,4 vs. 60,1±25,2 to 52,1±18,1 ml; P = 0,01; respectively), and decreased left atrium diastolic volume [69,0 (33,3-92,7) to 34,9 (41,1-60,9) vs. 44,6 (35,8- 73,3) to 45,6 (27,0-61,7) ml; P < 0,001; respectively). Quality of life in EMF-PT group improved after training when compared to EMF-Sed group (45±17 to 27±15 vs. 47 ± 20 to 45 ± 23 points; P < 0,05; respectively). CONCLUSION: These results point out that patients with EMF benefit from combined physical training emphasizing the importance of this nonpharmacological tool in the clinical treatment of these patients

INTRODUÇÃO: A doença de Chagas tem patogênese não totalmente conhecida. Ao contrário das funções sistólica e diastólica do ventrículo esquerdo, a função do átrio esquerdo carece de informações. OBJETIVOS: Em portadores de doença de Chagas, com ou sem alterações eletrocardiográficas, com ou sem disfunção sistólica de ventrículo esquerdo, verificar se há diferença nos parâmetros de função atrial esquerda e se há correlação entre dados de função de átrio esquerdo e parâmetros ecodopplercardiográficos de função ventricular sistólica e diastólica de ventrículo esquerdo MÉTODOS: 85 indivíduos: 10 controles (GC), 26 na forma indeterminada (GI), 30 com alterações eletrocardiográficas somente (GII) e 19 com disfunção ventricular (GIII), submetidos a ecocardiograma para avaliação da função atrial e das funções sistólicas e diastólicas ventriculares. Para analise estatística foi utilizado teste de Kruskal-Wallis e o coeficiente de Spearman. RESULTADOS: Função de reservatório (FET: fração de esvaziamento total): Houve diferença entre os grupos (p < 0,0001), média menor no GIII comparado ao GC (p = 0,003), ao GI (p < 0,001) e GII (p < 0,001), sem diferença entre GC, GI e GII. Fluxo de veias pulmonares: na onda S houve diferença entre os grupos (p = 0,003), média menor no GIII comparada ao GC (p = 0,01). Função de conduto (FEP: fração de esvaziamento passivo): houve diferença entre os grupos (p = 0,004), média menor no GIII, sem significância estatística comparando entre os grupos (GIII e GC, p = 0,06, GI e GII, p = 0,06, e GII e GIII, p = 0,07). Função de bomba propulsora (FEA: fração de esvaziamento ativo): houve diferença entre os grupos (p = 0,0001), média menor no GIII comparado ao GC (p = 0,05), ao GI (p < 0,0001) e ao GII (p = 0,002). Correlações: E/e\'média e FET: fraca correlação negativa (r = - 0,263; p = 0,02), moderada correlação negativa no GIII (r = - 0,58; p = 0,02). E/e\'média e FEP: não houve correlação (r = - 0,09; p = 0,44). E/e\'média e FEA: moderada correlação negativa (r = -0,36; p = 0,002) e no GIII (r = - 0,57; p = 0,04). e\'média e FET: moderada correlação positiva (r = 0,53; p < 0,0001). e\'média e FEP: moderada correlação positiva (r = 0,49; p < 0,0001). e\'média e FEA: moderada correlação positiva (r = 0,39; p = 0,001). Fração de ejeção do VE e FET: moderada correlação positiva (r = 0,35; p = 0,003) e no GIII (r = 0,52; p = 0,04). Fração de ejeção do VE e FEP: moderada correlação positiva (r = 0,42; p < 0,0001). Fração de ejeção do VE e FEA: moderada correlação positiva (r = 0,35; p = 0,003). CONCLUSÕES: Em pacientes com miocardiopatia chagásica com disfunção sistólica de ventrículo esquerdo, houve comprometimento das funções de reservatório, de conduto e bomba propulsora do átrio esquerdo e aqueles com função sistólica normal não apresentaram alterações nessas funções / BACKGROUND: Chagas disease (CD) pathogenesis is not fully known. Unlike the systolic and diastolic function of the left ventricle, the left atrial function still lacks information. OBJECTIVES: The aim of this study was to observe differences in patients with CD regarding the parameters of left atrial function and correlate them with Doppler echocardiographic parameters CASUISTIC AND METHODS: 85 subjects: 10 controls (GC), 26 in the indeterminate form (GI), 30 with ECG changes and normal left systolic function (GII) and 19 with left ventricular dysfunction (GIII) underwent echocardiography to assess left atrial and ventricular systolic and diastolic functions RESULTS: Reservoir function (TEF: total emptying fraction): there was a difference between groups (p <0.0001), lower mean in GIII compared to CG (p = 0.003), GI (p <0.001) and GII (p <0.001) with no difference between GC, GI and GII. Pulmonary veins flow: the S wave was no difference between groups (p = 0.003), lower mean in GIII compared to the CG (p = 0.01). Conduit function (PEF: passive emptying fraction): there was a difference between groups (p = 0.004), lower mean in GIII, without statistical significance between groups (GIII and GC, p = 0.06, GI and GII, p = 0.06, and GII and GIII, p = 0.07). Pump function (AEF: active emptying fraction): there was a difference between groups (p = 0.0001), lower mean in GIII compared to CG (p = 0.05), GI (p <0.0001) and GII (p = 0.002). Correlations: E/e\'mean and TEF: weak negative correlation (r = - 0.263, p = 0.02), moderate negative correlation in GIII (r = - 0.58, p = 0.02). E/e\'mean and PEF: no correlation (r = - 0.09, p = 0.44). E/e\'mean and AEF: moderate negative correlation (r = -0.36, p = 0.002) and GIII (r = - 0.57, p = 0.04). e\'mean and TEF: moderate positive correlation (r = 0.53, p <0.0001). e\'mean and PEF: moderate positive correlation (r = 0.49, p <0.0001). e\'mean and AEF: moderate positive correlation (r = 0.39, p = 0.001). LV ejection fraction and TEF: moderate positive correlation (r = 0.35, p = 0.003) and GIII (r = 0.52, p = 0.04). LV ejection fraction and PEF: moderate positive correlation (r = 0.42, p <0.0001). LV ejection fraction and AEF: moderate positive correlation (r = 0.35, p = 0.003). CONCLUSIONS: In patients with Chagas\' cardiomyopathy with left ventricular systolic dysfunction, there was impairment of the functions of reservoirs, conduit and pump of the left atrium

L’automatisme cardiaque est généré par un mécanisme fondamental partiellement compris et controversé, initié par des cardiomyocytes spécialisés dans le nœud sino-atrial (NSA). Ces cellules pacemaker (cNSA) présentent une phase spontanée de dépolarisation diastolique (DD), qui mène le potentiel de membrane de la fin de la repolarisation du potentiel d’action (PA) au seuil de déclenchement du PA suivant. Cette activité spontanée implique plusieurs canaux ioniques à la surface de la membrane plasmique et la dynamique calcique intracellulaire. Les cardiomyocytes contractiles du myocarde expriment majoritairement le canal calcique Cav1.2 tandis que les cNSA en expriment d’autres isoformes. Ce sont les canaux calciques de type L (LTCC) Cav1.3 et de type T (TTCC) Cav3.1, qui sont impliqués dans la DD. Les souris génétiquement modifiées pour Cav1.3 et/ou Cav3.1 ont des caractéristiques physiopathologiques et sont utilisées comme modèle d’étude des dysfonctions sinusales de l’homme. La cartographie optique du NSA isolé a permis de révéler une activité électrophysiologique intrinsèque altérée par les mutations. L’expérimentation en patch clamp et en imagerie calcique des cNSA isolées montrent que les mutations altèrent la mécanistique cellulaire du pacemaker. Le couplage de ces approches à l’utilisation d’outils pharmacologiques spécifiques a permis d’évaluer la contribution des différents éléments à cette mécanistique cellulaire et de préciser les controverses sur les fondements de l’automatisme cardiaque. Cette thématique de recherche présente des enjeux majeurs dans le domaine de la santé puisque les perspectives thérapeutiques et les stratégies pharmacologiques pour traiter les dysfonctions sinusales nécessitent une connaissance intégrale du mécanisme. / Heart automaticity is generated by a basic pacemaker mechanism not fully understood and still controversial. Pacemaker activity is initiated by specialized cardiomyocytes in the Sino-atrial node (SAN). The spontaneous phase of diastolic depolarization (DDP) characterizes SAN cells (SANc). This phase drives the membrane potential of SANc from the end of the repolarization to the threshold of the next action potential (AP). This spontaneous activity involves several ion channels on the plasma membrane and the intracellular dynamic of calcium. In terms of calcium channels, atrial and ventricular cardiomyocytes express mostly Cav1.2 whereas SANc express two additional isoforms. Specifically, in SANc are expressed Cav1.3 LTCC (L type Calcium channels) and the Cav3.1 TTCC (T type Calcium channels), which are activated during the DD. Genetically modified mice inactivated for Cav1.3, Cav3.1 and Cav1.3/Cav3.1 we generated and used as a models of study of human SAN dysfunctions. In particular, we highlighted the impairment of the pacemaker activity in these mice by optical mapping of the intact SAN, and by patch clamping and calcium imaging of isolated SANc. Coupling this approaches with pharmacological tools allowed us to evaluating the contribution of the various elements constituting to the pacemaker mechanism. This thematic of research presents major issues in terms of public health. Indeed, we need a better understanding of the pacemaker mechanism to develop pharmacological strategies against SAN dysfunction.