Both oxidative stress and inflammation are enhanced in chronic heart failure. Dysfunction of cardiac mitochondria is a hallmark of heart failure and a leading cause of oxidative stress, which in turn exerts detrimental effects on cellular components, including mitochondria themselves, thus generating a vicious circle. Oxidative stress also causes myocardial tissue damage and inflammation, contributing to heart failure progression. Furthermore, a subclinical inflammatory state may be caused by heart failure comorbidities such as obesity, diabetes mellitus or sleep apnoeas. Some markers of both oxidative stress and inflammation are enhanced in chronic heart failure and hold prognostic significance. For all these reasons, antioxidants or anti-inflammatory drugs may represent interesting additional therapies for subjects either at high risk or with established heart failure. Nonetheless, only a few clinical trials on antioxidants have been carried out so far, with several disappointing results except for vitamin C, elamipretide and coenzyme Q10. With regard to anti-inflammatory drugs, only preliminary data on the interleukin-1 antagonist anakinra are currently available. Therefore, a comprehensive, deep understanding of our current knowledge on oxidative stress and inflammation in chronic heart failure is key to providing some suggestions for future research on this topic.

BackgroundA thorough analysis of noncardiac determinants of mortality in heart failure (HF) is missing. Furthermore, evidence conflicts on the outcome of patients with HF and no or mild systolic dysfunction. We aimed to investigate the prevalence of noncardiac and cardiac causes of death in a cohort of chronic HF patients, covering the whole spectrum of systolic function.Methods and ResultsWe enrolled 2791 stable HF patients, classified into HF with reduced ejection fraction (HFrEF; left ventricular ejection fraction [EF] <40%), HR with midrange EF (HFmrEF; left ventricular EF 41–49%), or HF with preserved EF (HFpEF; left ventricular EF ≥50%), and followed up for all‐cause, cardiac, and noncardiac mortality (adjudicated as due to cancer, sepsis, respiratory disease, renal disease, or other causes). Over follow‐up of 39 months, adjusted mortality was lower in HFpEF and HFmrEF versus HFrEF (hazard ratio: 0.75 [95% CI, 0.67–0.84], P<0.001 for HFpEF; hazard ratio: 0.78 [95% CI, 0.63–0.96], P=0.017 for HFmrEF). HFrEF had the highest rates of cardiac death, whereas noncardiac mortality was similar across left ventricular EF categories. Noncardiac causes accounted for 62% of deaths in HFpEF, 54% in HFmrEF and 35% in HFrEF; cancer was twice as frequent as a cause of death in HFpEF and HFmrEF versus HFrEF. Yearly rates of noncardiac death exceeded those of cardiac death since the beginning of follow‐up in HFpEF and HFmrEF.ConclusionsNoncardiac death is a major determinant of outcome in stable HF, exceeding cardiac‐related mortality in HFpEF and HFmrHF. Comorbidities should be regarded as main therapeutic targets and objects of dedicated quality improvement initiatives, especially in patients with no or mild systolic dysfunction.

Ventricular remodeling occurs progressively in untreated patients after large myocardial infarction and in those with cardiomyopathy. The pathologic changes of increased left ventricular (LV) volume and perturbation in the LV chamber geometry involve not only the myocytes, but also the non-myocyte cells and the extracellular matrix. Inflammation, fibrosis, neuro-hormonal activation, and ongoing myocardial damage are the mechanisms underlying remodeling. The detection of an ongoing remodeling process by means of biomarkers such as cytokines, troponins, neurohormones, metalloproteinases, galectin-3, ST-2 and others, may hold a clinical value and could, to some extent, drive the therapeutical strategy in patients after a myocardial infarction or with heart failure. For this reason, there is an increasing interest in the development of new biomarkers and a great number of laboratory tests have been recently proposed, whose clinical usefulness, however, is not fully established yet.

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Background The contribution of the lung or the plant gain ( PG ; ie, change in blood gases per unit change in ventilation) to Cheyne‐Stokes respiration ( CSR ) in heart failure has only been hypothesized by mathematical models, but never been directly evaluated. Methods and Results Twenty patients with systolic heart failure (age, 72.4±6.4 years; left ventricular ejection fraction, 31.5±5.8%), 10 with relevant CSR (24‐hour apnea‐hypopnea index [ AHI ] ≥10 events/h) and 10 without ( AHI <10 events/h) at 24‐hour cardiorespiratory monitoring underwent evaluation of chemoreflex gain (CG) to hypoxia ( ) and hypercapnia ( ) by rebreathing technique, lung‐to‐finger circulation time, and PG assessment through a visual system. PG test was feasible and reproducible (intraclass correlation coefficient, 0.98; 95% CI , 0.91–0.99); the best‐fitting curve to express the PG was a hyperbola ( R 2 ≥0.98). Patients with CSR showed increased PG , (but not ), and lung‐to‐finger circulation time, compared with patients without CSR (all P <0.05). PG was the only predictor of the daytime AHI ( R =0.56, P =0.01) and together with the also predicted the nighttime AHI ( R =0.81, P =0.0003) and the 24‐hour AHI ( R =0.71, P =0.001). Lung‐to‐finger circulation time was the only predictor of CSR cycle length ( R =0.82, P =0.00006). Conclusions PG is a powerful contributor of CSR and should be evaluated together with the CG and circulation time to individualize treatments aimed at stabilizing breathing in heart failure.

In remote ischemic conditioning (RIC), several cycles of ischemia and reperfusion render distant organ and tissues more resistant to the ischemia-reperfusion injury. The intermittent ischemia can be applied before the ischemic insult in the target site (remote ischemic preconditioning), during the ischemic insult (remote ischemic perconditioning) or at the onset of reperfusion (remote ischemic postconditioning). The mechanisms of RIC have not been completely defined yet; however, these mechanisms must be represented by the release of humoral mediators and/or the activation of a neural reflex. RIC has been discovered in the heart, and has been arising great enthusiasm in the cardiovascular field. Its efficacy has been evaluated in many clinical trials, which provided controversial results. Our incomplete comprehension of the mechanisms underlying the RIC could be impairing the design of clinical trials and the interpretation of their results. In the present review we summarize current knowledge about RIC pathophysiology and the data about its cardioprotective efficacy.

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