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Secondary mitral regurgitation (MR) results from left ventricular dilatation and dysfunction. Quantification of secondary MR is challenging because of the underlying myocardial disease. Clinical and echocardiographic evaluation requires a multi-parametric approach. Severe secondary MR occurs in up to one-fourth of patients with heart failure with reduced ejection fraction, which is associated with a mortality rate of 40% to 50% in 3 years. Percutaneous edge-to-edge mitral valve repair (MitraClip) has emerged as an alternative to surgical valve repair to improve symptoms, functional capacity, heart failure hospitalizations, and cardiac haemodynamics. Further new transcatheter strategies addressing MR are evolving. The Carillion, Cardioband, and Mitralign devices were designed to reduce the annulus dilatation, which is a frequent and important determinant of secondary MR. Several transcatheter mitral valve replacement systems (Tendyne, CardiAQ-Edwards, Neovasc, Tiara, Intrepid, Caisson, HighLife, MValve System, and NCSI NaviGate Mitral) are emerging because valve replacement might be more durable compared with valve repair. In small studies, these interventional therapies demonstrated feasibility and efficiency to reduce MR and to improve heart failure symptoms. However, neither transcatheter nor surgical mitral valve repair or replacement has been proven to impact on the prognosis of heart failure patients with severe MR, which remains high with a mortality rate of 14-20% at 1 year. To date, the primary indication for treatment of secondary severe MR is the amelioration of symptoms, reinforcing the value of a Heart Team discussion. Randomized studies to investigate the treatment effect and long-term outcome for any transcatheter or surgical mitral valve intervention compared with optimized medical treatment are urgently needed and underway., (© 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with significant morbidity and mortality. Currently, atrial endocardial catheter ablation, mainly targeting focal discharges in the pulmonary veins, is the most widely used interventional treatment of drug-refractory AF. Despite technical improvements, results are not yet optimal. There is ongoing search for alternative and/or complementary interventional targets. Conditions associated with increased sympathetic activation such as hypertension, heart failure and sleep apnea lead to structural, neural and electrophysiological changes in the atrium thereby contributing to the progression from paroxysmal to persistent AF and increasing recurrence rate of AF after PVI. Until now, interventional modulation of autonomic nervous system was limited by highly invasive techniques. Catheter-based renal denervation (RDN) was introduced as a minimally invasive approach to reduce renal and whole body sympathetic activation with accompanying blood pressure control and left-ventricular morphological and functional changes in resistant hypertension. This review focuses on the potential atrial antiarrhythmic and antiremodeling effects of RDN in AF patients with hypertension, heart failure, and sleep apnea and discusses the possible role of RDN in the treatment of AF.

Chronic heart failure is associated with sympathetic activation characterised by elevated circulating norepinephrine levels linked to cardiovascular morbidity and mortality. Norepinephrine induces phenotype changes of the cardiomyocyte, fibrosis and β-adrenergic signal transduction defects implicated in the dysregulation of contractility. Renal denervation reduces left ventricular hypertrophy and improves diastolic dysfunction, partly blood pressure independently. Also, exercise tolerance and cardiac arrhythmias are positively influenced. Furthermore, there is evidence that common comorbidities like sleep apnoea, metabolic disease and microalbuminuria are improved following renal denervation. The available evidence suggests performing randomised controlled trials to scrutinise whether renal sympathetic denervation might be able to improve morbidity and mortality in chronic heart failure with preserved or reduced ejection fraction.

Heart failure is a frequent and life-threatening syndrome which is not only the result of myocardial injury or hemodynamic overload as commonly perceived, but appears to be the result of an interplay among genetic, neurohormonal, inflammatory, and biochemical factors, collectively referred to as biomarkers. Biomarkers can become risk factors in case their therapeutic modification results in an improvement of clinical outcomes. Among those markers identified in patients with heart failure, a number appears to have direct clinical relevance in aiding diagnosis, risk stratification, monitoring therapy, and treating to targets in order to improve clinical outcomes. These include brain natriuretic peptides (e.g., BNP, NT-proBNP), inflammatory markers (e.g., hsCRP), neurohormones (e.g., aldosterone), cardiorenal markers (e.g., cycstatin C), and novel markers (e.g., galectin-3). While their utility to indicate risk is mostly well established, there are less data to establish that a treatment using biomarkers as a guidance results in better outcomes than a more generalized intensified treatment of patients with heart failure. Future directions may involve larger platforms that facilitate to simultaneously analyze hundreds of biomarkers and may help to tailor heart failure therapy on a single patient basis, considering the specific pathogenesis and prognosis. Also from a therapeutic perspective there are data that a single intervention such as aldosterone blockade may affect multiple biomarkers at the same time. Taken together the data indicate that biomarkers are evolving into a valuable addendum to the diagnostic and therapeutic armamentarium.

Inflammation and pro-hypertrophic signaling are important for development and progression of myocardial hypertrophy (LVH) and chronic heart failure (CHF). Here we investigated the relevance of integrin-linked kinase (ILK) for chemokine receptor CXCR4- and angiotensin II type 1-triggered signaling and its regulation and role in cardiac remodeling. Using ELISA, real-time-PCR, and Western blotting, the present study demonstrates that SDF-1 and its receptor CXCR4 are up-regulated in plasma and left ventricles, respectively, in mouse models of cardiac hypertrophy (transaortic constriction, transgenic cardiac-specific overexpression of rac1) and in human CHF in association with increased cardiac ILK-expression. In isolated cardiomyocytes, ILK is activated by CXCR4-ligation and necessary for SDF-1-triggered activation of rac1, NAD(P)H oxidase, and release of reactive oxygen species. Importantly, the pro-hypertrophic peptide angiotensin II induces ILK-activation dependent on rac1 in cardiomyocytes, where ILK is necessary for angiotensin II-mediated stimulation of hypertrophy genes and protein synthesis. We conclude that in both SDF-1- and angiotensin II-triggered signaling, ILK is a central mediator of rac1-induced oxidative stress and myocardial hypertrophy., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Background Since kidney transplant recipients (KTRs) have a high cardiovascular disease burden, adequate risk prediction is of importance. Whether echocardiographic parameters and plasma biomarkers, natriuretic peptides [N-terminal pro-B-type natriuretic peptide (NT-proBNP)] and troponin T provide complementary or overlapping prognostic information on cardiovascular events remains uncertain. Methods The prospective Heterogeneity of Monocytes and Echocardiography Among Allograft Recipients in Nephrology (HOME ALONE) study followed 177 KTRs for 5.4 ± 1.7 years. Predefined endpoints were hospitalization for acute decompensated heart failure or all-cause death (HF/D) and major atherosclerotic cardiovascular events or all-cause death (MACE/D). At baseline, plasma NT-proBNP, plasma troponin T and echocardiographic parameters [left atrial volume index, left ventricular (LV) mass index, LV ejection fraction, and LV filling pressure] were assessed. Results Among all echocardiographic and plasma biomarkers measured, only NT-proBNP was consistently associated with HF/D in univariate and multivariate {third versus first tertile: hazard ratio [HR] 4.20 [95% confidence interval (CI) 1.02–17.27]} analysis, and only troponin T was consistently associated with MACE/D in univariate and multivariate [third versus first tertile: HR 8.15 (95% CI 2.75–24.18)] analysis. Conclusion Our data suggest that plasma biomarkers are robust and independent predictors of heart failure and atherosclerotic cardiovascular events after kidney transplantation, whereas standard echocardiographic follow-up does not add to risk prediction. [ABSTRACT FROM AUTHOR]

Aims Peripartum cardiomyopathy (PPCM) is associated with high mortality and morbidity. Endothelial damage involving cathepsin-D to form a 16 kDa prolactin (PRL) peptide is pathogenetically relevant. Inhibiting PRL peptide with bromocriptine has yielded promising results. We investigated whether microparticles (MPs) can be quantified in serum as markers for diagnosis and treatment effects in PPCM. Methods and results Patients with PPCM were compared with age-matched healthy post-partum women (PPCTR), healthy pregnant women (PCTR), healthy non-pregnant women (NPCTR), patients with ischaemic cardiomyopathy (ICM), patients with stable coronary artery disease (CAD) and healthy controls (HCTR). Peripartum cardiomyopathy treated with bromocriptine (PPCM-BR) and with PPCM without bromocriptine-treatment as control (PPCM-BRCTR) were compared. Microparticles were determined by flow cytometry. Endothelial MPs (EMPs) were elevated in PPCM compared with PPCTR, PCTR, and NPCTR, each P< 0.001. They were significantly elevated compared with ICM, CAD, and HCTR (P< 0.001). Pregnancy (PCTR) exhibited only slight increases vs. ICM, CAD, NPCTR, and HCTR. The increase in PPCM was due to an increase of activated but not apoptotic EMPs. Platelet-derived microparticles were highly increased in PPCM compared with ICM (P< 0.001) but 9.3 ± 4.4-fold compared with CAD (P< 0.001). In NPCTR (P< 0.001) compared with NPCTR, the increase was 5.9 ± 1.7-fold (P< 0.001). Microparticles generated from monocytes (MMPs) were increased 2.4 ± 1.8-fold in PPCM compared with PCTR (P< 0.001) and 4.8 ± 3.6-fold compared with CAD (P< 0.001), whereas leucocyte MPs (LMPs) were not significantly elevated. Endothelial microparticles were significantly reduced in PPCM treated additionally with bromocriptine compared with PPCM treated only with heart failure therapy (P< 0.001). Conclusion Microparticle profiles may in long-term distinguish PPCM from normal pregnancy, heart failure, and vascular diseases and might be a diagnostic marker related to the pathomechanism of PPCM. [ABSTRACT FROM PUBLISHER]