Central sleep apnea after acute coronary syndrome and association with ticagrelor use.

STUDY OBJECTIVES: By modifying the apneic threshold, the antiplatelet agent ticagrelor could promote central sleep apnea hypopnea syndrome (CSAHS). We aimed to assess the association between CSAHS and ticagrelor administration. METHODS: Patients were prospectively included within 1 year after acute coronary syndrome (ACS), if they had no heart failure (and left ventricular ejection fraction ≥ 45%) and no history of sleep apnea. After an overnight sleep study, patients were classified as "normal" with apnea hypopnea index (AHI) < 15, "CSAHS patients" with AHI ≥ 15 mostly with central sleep apneas, and "obstructive sleep apnea hypopnea syndrome (OSAHS) patients" with AHI ≥ 15 mostly with obstructive sleep apneas. RESULTS: We included 121 consecutive patients (mean age 56.8 ± 10.8, 88% men, mean body mass index 28.3 ± 4.4 kg/m2, left ventricular ejection fraction 56 ± 5%, at a mean of 67 ± 60 days (median 40 days, interquartile range: 30-80 days) after ACS. In total, 49 (45.3%) patients had AHI ≥ 15 (27 [22.3%] CSAHS %, 22 [18.2%] OSAHS). For 80 patients receiving ticagrelor, 24 (30%) had CSAHS with AHI ≥ 15, and for 41 patients not taking ticagrelor, only 3 (7.3%) had CSAHS with AHI ≥ 15 (chi-square = 8, p = 0.004). On multivariable analysis only age and ticagrelor administration were associated with the occurrence of CSAHS, (p = 0.0007 and p = 0.0006). CONCLUSION: CSA prevalence after ACS is high and seems promoted by ticagrelor administration. Results from monocentric study suggest a preliminary signal of safety. CLINICAL TRIALS. GOV ID: NCT03540459.

[BNP and echocardiography can predict the occurrence of acute cardiac decompensation during titration of bisoprolol in chronic systolic heart failure]. / Le BNP et l'échocardiographie prédisent la survenue de décompensation cardiaque aigue au cours de la titration du bisoprolol dans l'insuffisance cardiaque chronique systolique.

OBJECTIVES: Based on the fact that NYHA class, plasma BNP level, and echocardiographic indices of left ventricular filling pressures are prognostic factors in chronic systolic heart failure, we evaluated their predictive value for acute decompensation following initiation and titration of bisoprolol in this illness. METHODS AND RESULTS: Bisoprolol was initiated and/or increased according to the ESC/ACC/AHA recommendations in 50 patients with stable chronic systolic heart failure (age: 60+/-2 years, males: 88%) in NYHA class? 2 with a left ventricular ejection fraction (LVEF)<40% and a plasma creatinine<250 micromol/l. The clinical parameters, plasma BNP levels and echocardiographic indices were measured blind on the same day, on admission and then once a week for three weeks. On admission, the NYHA was 2.9+/-0.1, mean plasma creatinine 99+/-3 micromol/l, plasma BNP 503+/-57 pg/ml, LVEF 29+/-1%, E/A ratio 1.9+/-0.2, E/Ea ratio 8.8+/-0.3, E wave deceleration time 155+/-9 ms, systolic pulmonary artery pressure 40+/-2 mmHg and the diameter of the inferior vena cava was 16+/-1 mm. Over the course of follow up, an episode of acute decompensation occurred in 16% of the patients (8/50). Using univariate analysis, age and initial (admission) values for NYHA class, blood pressure, plasma BNP level, E/A ratio, E wave deceleration time, E/Ea ratio and the systolic pulmonary arterial pressure allowed prediction of the occurrence of acute decompensation following initiation and titration of bisoprolol. The use of the initial value of NYHA class alone allowed prediction of the occurrence of acute decompensation in just 56% of the patients, and the absence of an occurrence of acute decompensation in 93% of them. Normal results for the echocardiographic indices (systolic pulmonary arterial pressure<40 mmHg or E/A ratio<1.4 or E wave deceleration time>145 ms) as recorded on admission were associated with the absence of an occurrence of acute decompensation is 100% of cases. The combined use of NYHA class>3 and either a BNP>398 pg/ml or echocardiographic indices in favour of an elevation in left ventricular filling pressures (systolic pulmonary arterial pressure>40 mmHg, E/A ratio>1.4 or E wave deceleration time<145 ms) allowed prediction of the occurrence of acute heart failure in 100% of cases CONCLUSION: The combined use of NYHA class, BNP level and echocardiographic indices for measuring left ventricular filling pressures is more pertinent than the isolated use of clinical parameters for predicting tolerance to bisoprolol in chronic heart failure with a LVEF<40%.

[Exercise training in cardiac patients: usefulness of the cardiopulmonary exercise test]. / Réadaptation des patients porteurs d'une cardiopathie: intérêt de la mesure des echanges gazeux a l'effort (VO2).

Exercise training is currently including in the treatment of coronary arterial disease patients, in patients with left ventricular dysfunction as well as in patients who underwent cardiac transplantation or cardiac surgery. However methods of prescribing exercise-training programs are difficult to determine and must be adapted for each patient Exercise test with gas analysis through the determination of anaerobic threshold may help to understand the physiopathological mechanism related to exercise limitation in these patients. Exercise test may help to precise exercise intensity during cardiac rehabilitation and may assess the benefits on exercise tolerance.

[Heart failure and cachexia]. / Insuffisance cardiaque et cachexie.

Cachexia is related to a malnutrition state related to hypercatabolism. Initially described in cancer, it is also related to several chronic diseases including heart failure. Defined by an unintentional weight loss exceeding 7.5% of body mass during more than 6 months, it is presented by the association of nutritional deficiencies, digestive and/or urinary losses as well as metabolic abnormalities causing fat and lean mass loss and is associated to a poor prognosis. The pathophysiology of cachexia and heart failure presented some similarities associating especially neuro-hormonal activation, a cortisol/DHEA ratio imbalance, as well as pro-inflammatory cytokines activation. Currently the treatment of cachexia is mainly preventive, based on ACE-inhibitors and beta-blockers therapy and physical reconditioning. The benefits of hormonal and nutritional substitutes remains to be evidenced.

[Treatment of left intraventricular thrombosis with low molecular weight heparin]. / Traitement des thrombus intraventriculaires gauches par héparine de bas poids moléculaire.

UNLABELLED: Following the discovery of a left intra ventricular thrombus (LIVT), the classical approach consists of treatment with non-fractionated heparin (NFH) followed by oral anticoagulants. The use of NFH for this indication has only been evaluated in one open, non randomised study of 23 patients with no control group. Low molecular weight heparins (LMWH) have not been the object of any study although they are routinely used by certain teams. The objective of this study was to evaluate the feasibility of the use of LMWH in the treatment of left intra ventricular thrombus. This was an open, non randomised prospective study. All patients having a newly diagnosed LIVT between September 2000 and September 2002 were treated with enoxaparine (100 IU/kg twice daily) for an average duration of 13 days; replacement with fluindione was started on the fifth day. The progression of the LIVT was followed using twice weekly transthoracic echocardiography for 3 weeks. RESULTS: 19 LIVT were discovered in 2 years (13 complicating an anterior infarct and 6 with a dilated cardiomyopathy). The average area was between 2.64 +/- 0.41 cm2 and 0.43 +/- 0.21 cm2 (p < 0.0001). Thirteen out of 19 thrombi disappeared with treatment (68.5%). There was no thrombocytopenia or haemorrhage. One transient ischaemic attack was noted. CONCLUSION: This preliminary work shows that LMWH are well tolerated and effective to make a thrombus disappear or to reduce its size.

Enhanced flow-dependent vasodilatation after bed rest, a possible mechanism for orthostatic intolerance in humans.

We investigated the alteration in flow-dependent-dilatation in the orthostatic intolerance occurring after bed-rest deconditioning. Eight men [aged mean (SEM) 32 (2) years] underwent two consecutive periods of 7 days of head-down-tilt (HDT, -6 degrees) during bed rest. A control age and sex matched group [n = 8, 30 (2) years], maintained its usual physical activity. Blood flow velocity (BFV) and diameter (Doppler and echotracking systems) were measured in the brachial artery, under basal conditions and during the post ischaemic hyperaemia following occlusion. The increase in BFV post-ischaemia did not change before, during and after HDT but the relative increase in the diameter was greater on the 7th day of the HDT period than before HDT [+8.8(1.6)% compared to +3.7(1.0)%, P < 0.001]. After HDT, 11 of 16 standing tests (comprising eight subjects in the two HDT periods) had to be stopped because of orthostatic intolerance. The flow-dependent-dilatation measured at the end of HDT was negatively correlated with the post-bed-rest duration of orthostatic tolerance (r = 0.78, P < 0.01). After the sublingual administration of glyceryl trinitrate, there was no change in the increase in diameter. No significant changes were observed in the control group. Bed-rest deconditioning enhances the flow-dependent vasodilatation of large arteries and might contribute to the orthostatic intolerance observed following bed-rest.

Hemodynamic stresses induce endothelial dysfunction and remodeling of pulmonary artery in experimental compensated heart failure.

BACKGROUND: We hypothesized that, in compensated heart failure (HF), hemodynamic perturbations and their consequences exist in pulmonary artery (PA) despite the absence of any perturbation in thoracic aorta (TA). METHODS AND RESULTS: The left coronary artery was ligated in 20 male Wistar rats with compensated HF. Four months after ligation, these rats were compared with 20 sham-operated control rats. Blood pressure, velocity, viscosity, luminal diameter, and wall tensile and shear stresses were determined in PA and TA. Arterial rings were mounted in a myograph for ex vivo study. Endothelial nitric oxide synthase (eNOS) mRNA expression was determined in lung and aorta. Sections of PA and TA were used for histomorphometric study. In PA from rats with compensated HF, (1) blood pressure and wall tensile stress increased, whereas blood velocity and wall shear stress decreased; (2) contractions to KCl were not altered, but maximal contraction to phenylephrine and EC(50) decreased; (3) endothelium-dependent relaxation to acetylcholine and basal NO activity were blunted, whereas endothelium-independent relaxation was preserved; (4) eNOS mRNA levels and eNOS transcription in lung nuclei decreased; and (5) medial cross-sectional area, thickness, smooth muscle cell number, elastin, and collagen contents increased. Conversely, no such changes were found in TA from rats with compensated HF. CONCLUSIONS: In compensated HF induced by small myocardial infarction, hemodynamics, vascular wall function, and structure are altered in PA but preserved in TA. These results indicate that the pulmonary vascular bed is an early target of regional circulatory alterations in HF.

Enalapril improves arterial elastic properties in rats with myocardial infarction.

Systemic arterial elastic properties, important determinants of left ventricular function and coronary blood flow, are compromised in myocardial infarction (MI). The cardiac effect of angiotensin-converting enzyme inhibitors (ACEIs) has been extensively studied, whereas their arterial effect has been poorly reported in MI. The aim of this work was to study the effect of prolonged ACEI enalapril treatment on systemic arterial structure and elastic properties in rats with MI. One week after the induction of an MI, 40 male Wistar rats received either no treatment (n = 20) or ACEI enalapril (2 mg/kg; n = 20) for 17 weeks. At the end of the treatment period, blood pressure, cardiac output, total peripheral resistance, systemic arterial compliance, characteristic impedance, and left ventricular power were measured in anesthetized rats. Then the rats were killed for infarct-size determination and aortic histomorphometric study. Infarct size, heart, and left and right ventricular weights were similar in the ACEI-treated and untreated infarcted rats. Prolonged ACEI enalapril treatment reduced blood pressure by 17% (p < 0.001), total peripheral resistance by 22% (p < 0.01), and characteristic impedance by 26% (p < 0.03), and increased systemic arterial compliance by 35% (p < 0.01), in comparison with untreated infarcted rats. Enalapril reduced aortic media wall thickness by 9% (p < 0.02) and increased elastin content by 22% (p < 0.03) and elastin-to-collagen content ratio by 42% (p < 0.01). Enalapril did not affect cardiac output and left ventricular power. Smooth muscle cell nuclei number and size and collagen content of aortic wall were similar in the ACEI-treated and untreated infarcted rats. These results indicate that long-term treatment with ACEI enalapril improves arterial elastic properties through structural modifications of arterial wall in rats with MI. This vascular effect may contribute to improve the left ventricular function and the coronary perfusion of infarcted myocardium, and added to the cardiac effect, may explain the prevention of left ventricular remodeling observed with ACEI in this model.

Arterial expansive remodeling induced by high flow rates.

The effects of chronic increase in aortic blood flow on arterial wall remodeling were investigated in vivo with the use of an aortocaval fistula (ACF) model in rats. Phasic hemodynamics and aortic wall structure upstream and downstream in 30 male Wistar rats with ACF and 30 sham-operated rats were compared immediately and 2 mo after the ACF was opened in anesthetized rats. Opening the ACF upstream acutely decreased aortic pressure (-30%, P < 0.001) and increased aortic blood velocity (x12, P < 0.001), blood flow (x9, P < 0.001), wall shear stress (x10, P < 0.001) and guanosine 3',5'-cyclic monophosphate (cGMP) wall content (+50%, P < 0.01). After 2 mo, aortic pressure decreased (-22%, P < 0.001) and aortic blood velocity, diameter, and blood flow increased (+114%, P < 0.001; +60%, P < 0.001; and +250%, P < 0.001; respectively) compared with the control group. Aortic wall shear stress and cGMP wall content dropped over time and tended to recover control values; aortic wall tensile stress was higher than in the control group (P < 0.05). Medial cross-sectional area and elastin and collagen contents increased (+38%, P < 0.01; +50%, P < 0.01; and +30%, P < 0.05, respectively) and were associated with smooth muscle cell hypertrophy) (+23%, P < 0.05), despite a decrease in arterial wall thickness (-13%, P < 0.01). Opening the ACF downstream acutely decreased aortic pressure (-30%, P < 0.001) without any change in aortic blood velocity, diameter, blood flow, shear stress, and cGMP wall content. After 2 mo, pressure, blood velocity, shear stress, and cGMP wall content decreased (-22%, P < 0.001; -31%, P < 0.01; -46%, P < 0.02; and -50%, P < 0.05; respectively) and diameter and blood flow were unchanged; smooth muscle cell hypertrophy and hypoplasia were the only observed changes in the aortic wall structure. These results suggest that both shear and tensile stresses are involved in the aortic wall remodeling. Increase in shear stress likely induces expansive remodeling in relation to flow-dependent vasodilation, whereas increase in tensile stress is responsible for medial hypertrophy and fibrosis.