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Endothelial dysfunction and altered nitric oxide (NO) metabolism are considered causal factors in heart failure with preserved ejection fraction (HFpEF). NO synthase activity depends on the availability of arginine and its derivatives. Thus, we analyzed arginine, associated metabolites, arginine-metabolizing enzymes and NO turnover in 20-week-old female healthy lean (L-ZSF1) and obese ZSF1 rats (O-ZSF1) with HFpEF. Serum, urine and lysates of liver, kidney and heart were analyzed. There were significantly lower lysine (− 28%), arginine (− 31%), homoarginine (− 72%) and nitrite (− 32%) levels in serum of O-ZSF1 rats. Ornithine (+ 60%) and citrulline (+ 20%) levels were higher. Similar results were found in the heart. Expression of arginine consuming enzymes in liver and kidney was unchanged. Instead, we observed a 5.8-fold higher arginase 1 expression, presumably of granulocyte origin, in serum and > fourfold increased cardiac macrophage invasion in O-ZSF1. We conclude that inflammatory cells in blood and heart consume arginine and probably homoarginine via arginase 1 and inducible NO synthase and release ornithine and citrulline. In combination with evidence for decreased NO turnover in O-ZSF1 rats, we assume lower arginine bioavailability to endothelial NO synthase.

Aims Establishing a diagnosis of inflammatory cardiomyopathy (iCMP) by non-invasive means remains challenging despite advances in cardiac magnetic resonance imaging. Previous studies suggested the involvement of microRNAs in the pathogenesis of iCMP. We examined the association of a predefined set of circulatory microRNAs with clinical characteristics of iCMP and evaluated their diagnostic performance in suspected iCMP. Methods and results Eighty-nine patients with clinical suspicion of iCMP were included in the analysis. All patients underwent cardiac catheterization with left ventricular endomyocardial biopsy, echocardiography, and cardiac magnetic resonance imaging applying the Lake Louise criteria (LLC). Plasma levels of miR-21, miR-126, miR-133a, miR-146b, miR-155, and miR-206 were determined using real-time polymerase chain reaction. Based on immunohistological findings on endomyocardial biopsy, iCMP was diagnosed in 67% of study participants (n = 60). Plasma levels of miR-155 and miR-206 were significantly increased in patients with iCMP as compared with patients with dilated cardiomyopathy (P = 0.008 and P = 0.009, respectively). In receiver operating characteristic curve analysis, miR-155 and miR-206 demonstrated superior diagnostic performance for iCMP (0.68 and 0.67, respectively) compared with LLC [area under the curve (AUC) 0.60], Troponin T (AUC 0.51), and N-terminal pro-brain natriuretic peptide (AUC 0.51). While baseline miR-155 and miR-206 plasma levels were predictive for biopsy-proven iCMP (odds ratio = 2.61, 95% confidence interval = 1.28-5.31, P = 0.008 and odds ratio = 2.65, 95% confidence interval = 1.27-5.52, P = 0.009) on univariate logistic regression analysis, the presence of positive LLC, high baseline C-reactive protein, or presence of clinical symptoms and signs of viral infection failed to predict iCMP (P > 0.05, respectively). Conclusions The present data suggest that plasma levels of miR-206 and miR-155 are potential novel biomarkers for confirming the diagnosis of iCMP.

Six consecutive cases of persistent pulmonary hypertension of the newborn (PPHN) were treated with adenosine following failure of conventional therapy, excluding inhaled nitric oxide. A rise in arterial P_O2 >20 mm Hg occurred in 5 of 6 cases within 30 min of commencing adenosine infusion. Individual maximal increases in PaO₂ ranged from 31 to 131 mm Hg. Three neonates survived and 3 died. Amongst deaths, intensive support was withdrawn in a preterm neonate due to severe arthrogryposis/pulmonary hypoplasia. Of the remaining 2, the improvement in oxygenation persisted until death occurred from causes unrelated to adenosine. Side effects related to adenosine (bradycardia, hypotension, prolonged bleeding time) did not occur. Due to its ease of availability, administration and extremely short half-life, adenosine may be an important therapeutic option in PPHN.

BackgroundAtrial fibrillation (AF) is the most common sustained arrhythmia in clinical routine. Left atrial (LA) electro-anatomical remodelling in AF patients indicates disease progression and is associated with poor therapeutic success. PR interval prolongation is associated with an increased risk for AF, however, the association between LA remodelling measured as low voltage areas (LVA) during catheter ablation and PR interval is unknown. The aim of this study was to investigate the association between PR interval prolongation and LVA in AF patients.MethodsWe studied 103 patients (62±12 years, 59% males, 34% persistent AF) undergoing first AF catheter ablation and presenting with sinus rhythm. PR interval prolongation was defined as PR >200ms and analysed in resting ECG before intervention. LVA were determined using high-density maps and defined as <0.5 mV.ResultsThere were 24 patients (23%) with PR interval prolongation and 18 patients (17%) with LVA. There were significant correlations between PR prolongation with LVA, CHA2DS2-VASc score and eGFR (r2 = 0.230, 0.216, and 0.307, all p<0.05). PR interval prolongation (OR 3.450, p = 0.024), persistent AF (OR 5.391, p = 0.002), and LA size (OR 1.117, p = 0.018) were significant predictors for LVA, while age (OR 1.072, p = 0.005), LVA (OR 3.450 p = 0.024) and eGFR (OR 0.962, p = 0.004) were associated with PR interval prolongation.ConclusionsBeside persistent AF and LA size, PR interval prolongation might be useful for the prediction of electro-anatomical substrate in AF patients. Larger studies are needed to confirm these results.