Heart failure (HF) is a clinical syndrome of exercise intolerance and/or congestion. The optimal medical therapy of heart failure with reduced ejection fraction (HFrEF) includes angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and mineralocorticoid receptor antagonists, plus a diuretic, which has improved over the last decades. The recent PARADIGM-HF trial compared the novel compound LCZ696, a combination of the angiotensin receptor blocker valsartan and the neprilysin inhibitor sacubitril, versus the enalapril in 8,442 patients with symptomatic chronic HFrEF. LCZ696 led to a 20% reduction in the rate of death or hospitalization for HF and a 16% reduction in the rate of all-cause death at 3.5 years of follow-up. Accumulating evidence supports augmentation of cyclic guanosine monophosphate (cGMP) signalling as a potential therapeutic strategy for HF. Direct soluble guanylate cyclase (sGC) stimulators target reduced cGMP generation due to insufficient sGC stimulation and represent a promising method for cGMP enhancement. In addition, several preclinical or early phase studies which are currently investigating new mechanisms for matrix, intracellular calcium and energy regulation including the role of microRNAs, renal denervation, and new devices are presented and discussed.
　　The management of patients with heart failure and preserved ejection fraction (HFpEF) remains challenging and requires an accurate diagnosis. This portion of HFpEF population consists predominantly older age and high prevalence of co-morbidities such as obesity, diabetes mellitus, hyperlipidemia, metabolic syndrome and hypertension. Little progress has been made in identifying evidence-based, effective treatments for HFpEF. The mainstay of treatment is diuretics to reduce volume overload and improve dyspnea. Patients with an acute exacerbation of HFpEF and rapid atrial fibrillation (AF) should be rate controlled with negative chronotropic agents. For chronic therapy, treatments proven effective in HFrEF have failed to show significant benefit in patients with HFpEF. Chronic management can be simplified by using three strategies based on applicability: treat precipitating conditions (e.g., hypertension, AF), control symptoms by maintaining euvolemia with diuretics, and avoid therapies that have been shown not to be beneficial unless another compelling indication exists. Future outcome trials testing the efficacy of promising new agents will have better characterization of patient phenotype to maximize the potential response to therapies.