Magri D.,University of Rome La Sapienza |
Re F.,San Camillo Forlanini Hospital |
Limongelli G.,The Second University of Naples |
Agostoni P.,Monzino Cardiologic Center |
And 17 more authors.
Circulation Journal | Year: 2016
Background: Heart failure (HF) progression and its complications represent major emergent concerns in hypertrophic cardiomyopathy (HCM). We investigated the possible adjunctive role of cardiopulmonary exercise testing (CPET) in predicting HF-related events. An exercise-derived risk model, the HYPertrophic Exercise-derived Risk HF (HYPERHF), has been developed. Methods and Results: A multicenter cohort of 620 consecutive HCM outpatients was recruited and followed (2007 to 2015). The endpoint was death from HF, cardiac transplantation, NYHA III–IV class progression, severe functional deterioration leading to hospitalization for septal reduction, and hospitalization for HF worsening. During a median follow-up of 3.8 years (25–75th centile: 2.3–5.3 years), 84 patients reached the endpoint. Peak circulatory power (peak oxygen consumption * peak systolic blood pressure), ventilatory efficiency and left atrial diameter were independently associated with the endpoint and, accordingly, integrated into the HYPERHF model (C index: 0.849; best cutoff value equal to 15%). Conclusions: CPET is useful in the evaluation of HCM patients. In this context, the HYPERHF score might allow early identification of those patients at high risk of HF progression and its complications. © 2016, Japanese Circulation Society. All rights reserved.
Nobili E.,Monzino Cardiologic Center |
Nobili E.,University of Milan |
Salvado M.D.,Karolinska Institutet |
Folkersen L.,Karolinska Institutet |
And 10 more authors.
PLoS ONE | Year: 2012
Background: Cysteinyl-leukotrienes (cys-LT) are powerful spasmogenic and immune modulating lipid mediators involved in inflammatory diseases, in particular asthma. Here, we investigated whether cys-LT signaling, in the context of atherosclerotic heart disease, compromises the myocardial microcirculation and its response to hypoxic stress. To this end, we examined Apoe-/- mice fed a hypercholesterolemic diet and analysed the expression of key enzymes of the cys-LT pathway and their receptors (CysLT1/CysLT2) in normal and hypoxic myocardium as well as the potential contribution of cys-LT signaling to the acute myocardial response to hypoxia. Methods and principal findings: Myocardial biopsies from Apoe-/- mice demonstrated signs of chronic inflammation with fibrosis, increased apoptosis and expression of IL-6, as compared to biopsies from C57BL/6J control mice. In addition, we found increased leukotriene C4 synthase (LTC4S) and CysLT1 expression in the myocardium of Apoe-/- mice. Acute bouts of hypoxia further induced LTC4S expression, increased LTC4S enzyme activity and CysLT1 expression, and were associated with increased extension of hypoxic areas within the myocardium. Inhibition of cys-LT signaling by treatment with montelukast, a selective CysLT1 receptor antagonist, during acute bouts of hypoxic stress reduced myocardial hypoxic areas in Apoe-/- mice to levels equal to those observed under normoxic conditions. In human heart biopsies from 14 patients with chronic coronary artery disease mRNA expression levels of LTC4S and CysLT1 were increased in chronic ischemic compared to non-ischemic myocardium, constituting a molecular basis for increased cys-LT signaling. Conclusion: Our results suggest that CysLT1 antagonists may have protective effects on the hypoxic heart, and improve the oxygen supply to areas of myocardial ischemia, for instance during episodes of sleep apnea. © 2012 Nobili et al.