Europace. 2009 Jun 25; Bortone A, Boveda S, Pasquié JL, Pujadas-Berthault P, Marijon E, Appetiti A, Albenque JPAims In the setting of congestive heart failure (CHF), atrial fibrillation (AF) ablation can improve clinical status and the left ventricular ejection fraction (LVEF) value. However, the impact of AF ablation on the implantable cardioverter defibrillator (ICD) indication has never been specifically addressed. Methods and results Study subject were six CHF (mean age 61.1 +/- 6.9 years, mean LVEF 25.8 +/- 7.3%) patients refractory to conventional medical treatment with long-lasting AF unresponsive to external cardioversion. Five patients had an idiopathic dilated cardiomyopathy (DCM) and one had an ischaemic cardiomyopathy (ICM). Their New York Heart Association (NYHA) class was III-IV. Two patients had renal insufficiency. No patient had left ventricular delay. All patients underwent AF ablation. LVEF and NYHA class were dramatically improved in the five DCM patients. New York Heart Association class, but not the LVEF, was improved in the ICM patient. A redo ablative procedure was undertaken in four of five DCM patients and in the ICM patient due to arrhythmia recurrence. Left ventricular ejection fraction and NYHA were improved again in the DCM patients (56 +/- 4.4%, I-II, respectively) and led to ICD indication preclusion. The LVEF remained low in the ICM patient (30%) and led to ICD insertion. Sinus rhythm has been stable during the 18.1 +/- 5.7 months follow-up period. Conclusion Atrial fibrillation ablation in CHF patients can improve both the clinical status of patients and their LVEF, especially among those affected by DCM. The LVEF improvement has the potential to preclude the indication for a primary prevention ICD insertion.

Am J Physiol Heart Circ Physiol. 2009 Jun 19; Casals G, Ros J, Sionis A, Davidson MM, Morales-Ruiz M, Jimenez WB-type natriuretic peptide (BNP) is a peptide hormone of myocardial origin with significant cardioprotective properties. Patients with myocardial ischemia present with high levels of BNP in plasma and elevated expression in the myocardium. However, molecular mechanisms of BNP induction in the ischemic myocardium are not well understood. The aim of the investigation was to assess whether myocardial hypoxia induces the production of BNP in human ventricular myocytes. To test the hypothesis that reduced oxygen tension can directly stimulate BNP gene expression and release in the absence of hemodynamic or neurohormonal stimuli, we used an in vitro model system of cultured human ventricular myocytes (AC16 cells). Cells were cultured under normoxic (21% O2) or hypoxic (5% O2) conditions for up to 48 hours. Then, accumulation of BNP, Atrial Natriuretic Peptide (ANP) and Vascular Endothelial Growth Factor (VEGF) was measured. Hypoxia stimulated protein release of BNP and VEGF but not of ANP. In concordance, increased mRNA levels of BNP and VEGF but not of ANP were found on culturing AC16 cells under hypoxic conditions. The analysis of the transcriptional activity of the hypoxia inducible factor 1 (HIF-1) in nuclear extracts showed that HIF-1 activity was induced under hypoxic conditions. Finally, treatment of AC16 cells with the HIF-1 inhibitor rotenone in hypoxia inhibited BNP and VEGF release. In conclusion, these data indicate that hypoxia induces the synthesis and secretion of BNP in human ventricular myocytes, likely through HIF-1 enhanced transcriptional activity. Key words: natriuretic peptides, HIF-1, myocardial ischemia, heart failure.

J Am Coll Cardiol. 2009 Jun 30; 54(1): 36-46Tan YT, Wenzelburger F, Lee E, Heatlie G, Leyva F, Patel K, Frenneaux M, Sanderson JEOBJECTIVES: The purpose of this study was to test the hypothesis that in heart failure with normal ejection fraction (HFNEF) exercise limitation is due to combined systolic and diastolic abnormalities, particularly involving ventricular twist and deformation (strain) leading to reduced ventricular suction, delayed untwisting, and impaired early diastolic filling. BACKGROUND: A substantial proportion of patients with heart failure have a normal left ventricular ejection fraction. Currently the pathophysiology is considered to be due to abnormal myocardial stiffness and relaxation. METHODS: Patients with a diagnosis of HFNEF and proven cardiac limitation by cardiopulmonary exercise testing were studied by standard, tissue Doppler, and speckle tracking echocardiography at rest and on submaximal exercise. RESULTS: Fifty-six patients (39 women; mean age 72 +/- 7 years) with a clinical diagnosis of HFNEF and 27 age-matched healthy control subjects (19 women; mean age 70 +/- 7 years) had rest and exercise images of sufficient quality for analysis. At rest, systolic longitudinal and radial strain, systolic mitral annular velocities, and apical rotation were lower in patients, and all failed to rise normally on exercise. Systolic longitudinal functional reserve was also significantly lower in patients (p < 0.001). In diastole, patients had reduced and delayed untwisting, reduced left ventricular suction at rest and on exercise, and higher end-diastolic pressures. Mitral annular systolic and diastolic velocities, systolic left ventricular rotation, and early diastolic untwist on exercise correlated with peak VO(2)max. CONCLUSIONS: In HFNEF there are widespread abnormalities of both systolic and diastolic function that become more apparent on exercise. HFNEF is not an isolated disorder of diastole.

Horm Metab Res. 2009 Jun 19; Sivukhina EV, Poskrebysheva AS, Smurova IV, Dolzhikov AA, Morozov IE, Jirikowski GF, Grinevich VNeuroendocrine factors play an important role in the pathogenesis of chronic heart failure. Despite numerous clinical and experimental studies, the role of the hypothalamic-pituitary-adrenal axis and glucocorticoid hormones is not fully characterised. Here we present a study of plasma cortisol concentration in 74 chronic heart failure patients, divided into four groups based on NYHA functional classes I-IV, and in 17 control subjects. In parallel, we performed morphological analysis of the hypothalamic-pituitary-adrenal axis components from 8 male patients who had died from chronic heart failure, and 9 male controls. In our study we applied immunohistochemical method and quantitative analysis to investigate an expression of hypothalamic neurohormones (corticotropin-releasing hormone, vasopressin) and adrenocorticotropin hormone in the pituitary, as well as performed general histological examination of the adrenal cortex. Measurement of morning cortisol concentration in plasma of chronic heart failure patients revealed neither difference compared to controls nor with the severity of the disease. Despite this, a two-fold increase in the density of corticotropin-releasing hormone-immunoreactive neurons as well as a two-fold increase in the number of corticotropin-releasing hormone neurons co-expressing vasopressin in the hypothalamic paraventricular nucleus were found. In the anterior pituitary the density of adrenocorticotropin hormone-immunoreactive cells was significantly increased. General histological analysis of the adrenal cortex revealed a drastic thinning of the zona fasciculata and dystrophic changes in corticocytes. Structural changes, observed in the adrenal cortex, suggest a relative glucocorticoid deficiency, which may contribute to corticotropin-releasing hormone and adrenocorticotropin hormone upregulation in hypothalamus and pituitary of chronic heart failure patients.