Natriuretic Peptides in Heart Failure with Preserved Left Ventricular Ejection Fraction: From Molecular Evidences to Clinical Implications.

The incidence of heart failure with preserved ejection fraction (HFpEF) is increasing and its challenging diagnosis and management combines clinical, imagistic and biological data. Natriuretic peptides (NPs) are hormones secreted in response to myocardial stretch that, by increasing cyclic guanosine monophosphate (cGMP), counteract myocardial fibrosis and hypertrophy, increase natriuresis and determine vasodilatation. While their role in HFpEF is controversial, most authors focused on b-type natriuretic peptides (BNPs) and agreed that patients may show lower levels. In this setting, newer molecules with an increased specificity, such as middle-region pro-atrial natriuretic peptide (MR-proANP), emerged as promising markers. Augmenting NP levels, either by NP analogs or breakdown inhibition, could offer a new therapeutic target in HFpEF (already approved in their reduced EF counterparts) by increasing the deficient cGMP levels found in patients. Importantly, these peptides also retain their prognostic value. This narrative review focuses on NPs' physiology, diagnosis, therapeutic and prognostic implication in HFpEF.

The Predictive Role of the Biomarker Kidney Molecule-1 (KIM-1) in Acute Kidney Injury (AKI) Cisplatin-Induced Nephrotoxicity.

Acute kidney injury (AKI) following platinum-based chemotherapeutics is a frequently reported serious side-effect. However, there are no approved biomarkers that can properly identify proximal tubular injury while routine assessments such as serum creatinine lack sensitivity. Kidney-injury-molecule 1 (KIM-1) is showing promise in identifying cisplatin-induced renal injury both in vitro and in vivo studies. In this review, we focus on describing the mechanisms of renal tubular cells cisplatin-induced apoptosis, the associated inflammatory response and oxidative stress and the role of KIM-1 as a possible biomarker used to predict cisplatin associated AKI.

Left Atrial Structural Remodelling in Non-Valvular Atrial Fibrillation: What Have We Learnt from CMR?

Left atrial structural, functional and electrical remodelling are linked to atrial fibrillation (AF) pathophysiology and mirror the phrase "AF begets AF". A structurally remodelled left atrium (LA) is fibrotic, dysfunctional and enlarged. Fibrosis is the hallmark of LA structural remodelling and is associated with increased risk of stroke, heart failure development and/or progression and poorer catheter ablation outcomes with increased recurrence rates. Moreover, increased atrial fibrosis has been associated with higher rates of stroke even in sinus-rhythm individuals. As such, properly assessing the fibrotic atrial cardiomyopathy in AF patients becomes necessary. In this respect, late-gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging is the gold standard in imaging myocardial fibrosis. LA structural remodelling extension offers both diagnostic and prognostic information and influences therapeutic choices. LGE-CMR scans can be used before the procedure to better select candidates and to aid in choosing the ablation technique, during the procedure (full CMR-guided ablations) and after the ablation (to assess the ablation scar). This review focuses on imaging several LA structural remodelling CMR parameters, including size, shape and fibrosis (both extension and architecture) and their impact on procedure outcomes, recurrence risk, as well as their utility in relation to the index procedure timing.

Cardiac Optogenetics in Atrial Fibrillation: Current Challenges and Future Opportunities.

Although rarely life-threatening on short term, atrial fibrillation leads to increased mortality and decreased quality of life through its complications, including heart failure and stroke. Recent studies highlight the benefits of maintaining sinus rhythm. However, pharmacological long-term rhythm control strategies may be shadowed by associated proarrhythmic effects. At the same time, electrical cardioversion is limited to hospitals, while catheter ablation therapy, although effective, is invasive and is dedicated to specific patients, usually with low amounts of atrial fibrosis (preferably Utah I-II). Cardiac optogenetics allows influencing the heart's electrical activity by applying specific wavelength light pulses to previously engineered cardiomyocytes into expressing microbial derived light-sensitive proteins called opsins. The resulting ion influx may give rise to either hyperpolarizing or depolarizing currents, thus offering a therapeutic potential in cardiac electrophysiology, including pacing, resynchronization, and arrhythmia termination. Optogenetic atrial fibrillation cardioversion might be achieved by inducing a conduction block or filling of the excitable gap. The authors agree that transmural opsin expression and appropriate illumination with an exposure time longer than the arrhythmia cycle length are necessary to achieve successful arrhythmia termination. However, the efficiency and safety of biological cardioversion in humans remain to be seen, as well as side effects such as immune reactions and loss of opsin expression. The possibility of delivering pain-free shocks with out-of-hospital biological cardioversion is tempting; however, there are several issues that need to be addressed first: applicability and safety in humans, long-term behaviour, anticoagulation requirements, and fibrosis interactions.

Arterial Hypertension and Interleukins: Potential Therapeutic Target or Future Diagnostic Marker?

Hypertension as a multifactorial pathology is one of the most important cardiovascular risk factors, affecting up to 30-40% of the general population. Complex immune responses are involved in the inflammatory mechanism of hypertension, with evidence pointing to increased inflammatory mediators even in prehypertensive patients. Increased vascular permeability, thrombogenesis, and fibrosis, effects that are associated with sustained hypertension, could be attributed to chronic inflammation. Chronic inflammation triggers endothelial dysfunction via increased production of ROS through proinflammatory cytokines. Increased serum level of proinflammatory cytokines such as IL-1ß, IL-6, IL-8, IL-17, IL-23, TGFß, and TNFα in hypertensive patients has been associated with either increased blood pressure values and/or end-organ damage. Moreover, some cytokines (i.e., IL-6) seem to determine a hypertensive response to angiotensin II, regardless of blood pressure values. Understanding hypertension as an inflammatory-based pathology gives way to new therapeutic targets. As such, conventional cardiovascular drugs (statins, calcium channels blockers, and ACEIs/ARBs) have shown additional anti-inflammatory effects that could be linked to their blood pressure lowering properties. Moreover, anti-inflammatory drugs (mycophenolate mofetil) have been shown to decrease blood pressure in hypertensive patients or prevent its development in normotensive individuals. Further research is needed to evaluate whether drugs targeting hypertensive-linked proinflammatory cytokines, such as monoclonal antibodies, could become a new therapeutic option in treating arterial hypertension.