Progression of Left Ventricular Dysfunction and Remodelling under Optimal Medical Therapy in CHF Patients: Role of Individual Genetic Background

Background. Neurohormonal systems play an important role in chronic heart failure (CHF). Due to interindividual heterogeneity in the benefits of therapy, it may be hypothesized that polymorphisms of neurohormonal systems may affect left ventricular (LV) remodelling and systolic function. We aimed to assess whether genetic background of maximally treated CHF patients predicts variations in LV systolic function and volumes. Methods and Results. We prospectively studied 131 CHF outpatients on optimal treatment for at least six months. Echocardiographic evaluations were performed at baseline and after 12 months. Genotype analysis for ACE I/D, β1adrenergic receptor (AR) Arg389Gly, β2AR Arg16Gly, and β2AR Gln27Glu polymorphisms was performed. No differences in baseline characteristics were detected among subgroups. ACE II was a significant predictor of improvement of LV end-diastolic and end-systolic volume (P = .003 and P = .002, respectively) but not of LV ejection fraction (LVEF); β1AR389 GlyGly was related to improvement of LVEF (P = .02) and LV end-systolic volume (P = .01). The predictive value of polymorphisms remained after adjustment for other clinically significant predictors (P < .05 for all). Conclusions. ACE I/D and β1AR Arg389Gly polymorphisms are independent predictors of reverse remodeling and systolic function recovery in CHF patients under optimal treatment

The influence of confounders in the analysis of mid-regional pro-atrial natriuretic peptide in patients with chronic heart failure

Natriuretic peptides play an important role in the diagnosis and risk stratification of patients with acute and chronic heart failure. Multiple studies have shown that these peptides are liable to the influence of individual factors. For N-terminal-pro-B-type natriuretic peptide (NT-proBNP) some of these confounding factors have been evaluated over the years such as age, gender, New York Heart Association (NYHA) class and body mass index (BMI). The aim of this study was to establish confounding factors of mid-regional pro-atrial natriuretic peptide (MR-proANP) assessment

Ambient air pollution as a new risk factor for cardiovascular diseases: Time to take action

Air pollution is a recently recognized risk factor for cardiovascular disease

Emerging strategies for chronic heart failure: the role of gene therapy

Heart failure (HF) is a complex clinical syndrome and a major growing public health problem in Western countries. HF is a leading cause of death and morbidity in modern society, and its incidence continues to increase with the aging population. The complexity of this syndrome and its multifactorial origin constitute problems in the management of patients. Pharmacological treatments aim to interfere with the activation of the neurohormonal and adrenergic systems, which are key pathophysiological mechanisms underlying disease progression. Despite the improvements achieved by current therapies, patients in end stages of the disease still have a poor prognosis. Gene therapy represents a new approach to the treatment of HF, with the ambitious aim of repairing the molecular abnormalities that lead to the disease. Current medical management of clinical HF and novel gene therapies for treatment of HF are presented here

Cardiorenal Syndrome Type 1 Pathophysiological Crosstalk Leading to Combined Heart and Kidney Dysfunction in the Setting of Acutely Decompensated Heart Failure

Cardiorenal syndrome (CRS) type 1 is characterized as the development of acute kidney injury (AKI) and dysfunction in the patient with acute cardiac illness, most commonly acute decompensated heart failure (ADHF). There is evidence in the literature supporting multiple pathophysiological mechanisms operating simultaneously and sequentially to result in the clinical syndrome characterized by a rise in serum creatinine, oliguria, diuretic resistance, and in many cases, worsening of ADHF symptoms. The milieu of chronic kidney disease has associated factors including obesity, cachexia, hypertension, diabetes, proteinuria, uremic solute retention, anemia, and repeated subclinical AKI events all work to escalate individual risk of CRS in the setting of ADHF. All of these conditions have been linked to cardiac and renal fibrosis. In the hospitalized patient, hemodynamic changes leading to venous renal congestion, neurohormonal activation, hypothalamic-pituitary stress reaction, inflammation and immune cell signaling, systemic endotoxemic exposure from the gut, superimposed infection, and iatrogenesis all contribute to CRS type 1. The final common pathway of bidirectional organ injury appears to be cellular, tissue, and systemic oxidative stress that exacerbate organ function. This review explores in detail the pathophysiological pathways that put a patient at risk and then effectuate the vicious cycle now recognized as CRS type 1. (J Am Coll Cardiol 2012;60:1031–42) © 2012 by the American College of Cardiology Foundation Combined disorders of heart and kidney are today classifie

Fill in the Gaps of Secondary Mitral Regurgitation: a Continuum Challenge From Pathophysiology to Prognosis

Purpose of Review: Mitral regurgitation (MR) is one of the most frequent valvular heart diseases encountered in clinical practice. In contrast to primary MR, less is still known about the pathophysiology, diagnosis, and prognosis of secondary MR. The purpose of this report is to provide a review, upon the last knowledge reported in the literature, on the role and management of secondary MR in clinical practice. Recent Findings: Recent data highlight secondary MR not as a single pathological entity but as a wide spectrum of interconnected conditions which portend poor outcome. Although the role of secondary MR on clinical outcome is debated, recent available data suggest an independent association of MR with prognosis. Nevertheless, available treatment did not show a clear benefit after MR correction. Summary: Further studies are needed to better categorize and assess secondary MR beyond schematic classification. A management approach should be tailored upon each clinical context of presentation

Risk stratification in heart failure with mild reduced ejection fraction. European Journal of Preventive Cardiology

Heart failure with mid-range ejection fraction represents a heterogeneous and relatively young heart failure category accounting for nearly 20-30% of the overall heart failure population. Due to its complex phenotype, a reliable clinical picture of heart failure with mid-range ejection fraction patients as well as a definite risk stratification are still relevant unsolved issues. In such a context, there is growing interest in a comprehensive functional assessment by means of a cardiopulmonary exercise test, yet considered a cornerstone in the clinical management of patients with heart failure and reduced ejection fraction. Indeed, the cardiopulmonary exercise test has also been found to be particularly useful in the heart failure with mid-range ejection fraction category, several cardiopulmonary exercise test-derived parameters being associated with a poor outcome. In particular, a recent contribution by the metabolic exercise combined with cardiac and kidney indexes research group showed an independent association between the peak oxygen uptake and pure cardiovascular mortality in a large cohort of recovered heart failure with mid-range ejection fraction patients. Contextually, the same study supplied an easy approach to identify a high-risk heart failure with mid-range ejection fraction subset by using a combination of peak oxygen uptake and ventilatory efficiency cut-off values, namely 55% of the maximum predicted and 31, respectively. Thus, looking at the above-mentioned promising results and waiting for specific trials, it is reasonable to consider cardiopulmonary exercise test assessment as part of the heart failure with mid-range ejection fraction work-up in order to identify those patients with an unfavourable functional profile who probably deserve a close clinical follow-up and, probably, more aggressive therapeutic strategies