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AIMS: Pericardial effusion (PE) is a common finding in cardiac patients with chronic heart failure. The prognostic relevance of a small, haemodynamically non-compromising PE in such patients, however, remains to be determined. METHODS AND RESULTS: All patients referred to our heart failure clinic and having a baseline echocardiography and follow-up clinical visits were included. Patients with a haemodynamically relevant PE, acute myo-/pericarditis, systemic sclerosis, rheumatoid arthritis, heart transplantation, heart surgery within the last 6 months or malignancies within the last 3 years were excluded. Patients with or without a haemodynamically irrelevant PE were compared regarding all-cause mortality as the primary and cardiovascular death or need for heart transplantation as secondary outcomes. A total of 897 patients (824 patients in the control vs. 73 patients in the PE group) were included. In the PE group, left ventricular ejection fraction (LVEF) was lower [31%, interquartile range (IQR): 18.0-45.0] than in controls (34%, IQR: 25.0-47.0; P = 0.04), while the end-systolic diameters of the left ventricle and the left atrium were larger (P = 0.01 and P = 0.001, respectively). Similarly, in patients with PE, the right ventricle (RV) systolic function was lower (P < 0.005 for both the fractional area change and the tricuspid annulus movement), the dimensions of RV and right atrium (RA) were larger (P < 0.05 for RV and P < 0.01 for RA), and the degree of tricuspid regurgitation was higher (P < 0.0001). Furthermore, in the PE group, the heart rate was higher (P < 0.001) and the leukocyte count as well as CRP values were increased (P = 0.004 and P < 0.0001, respectively); beta-blocker use was less frequent (P = 0.04), while spironolactone use was more frequent (P = 0.03). The overall survival was reduced in the PE group compared with controls (P = 0.02). Patients with PE were more likely to suffer cardiovascular death (1-year estimated event-free survival: 86 +

AimsFlavanol-rich chocolate (FRC) is beneficial for vascular and platelet function by increasing nitric oxide bioavailability and decreasing oxidative stress. Congestive heart failure (CHF) is characterized by impaired endothelial and increased platelet reactivity. As statins are ineffective in CHF, alternative therapies are a clinical need. We therefore investigated whether FRC might improve cardiovascular function in patients with CHF.Methods and resultsTwenty patients with CHF were enrolled in a double-blind, randomized placebo-controlled trial, comparing the effect of commercially available FRC with cocoa-liquor-free control chocolate (CC) on endothelial and platelet function in the short term (2 h after ingestion of a chocolate bar) and long term (4 weeks, two chocolate bars/day). Endothelial function was assessed non-invasively by flow-mediated vasodilatation of the brachial artery. Flow-mediated vasodilatation significantly improved from 4.98 ± 1.95 to 5.98 ± 2.32% (P = 0.045 and 0.02 for between-group changes) 2h after intake of FRC to 6.86 ± 1.76% after 4 weeks of daily intake (P = 0.03 and 0.004 for between groups). No effect on endothelial-independent vasodilatation was observed. Platelet adhesion significantly decreased from 3.9 ± 1.3 to 3.0 ± 1.3% (P = 0.03 and 0.05 for between groups) 2 h after FRC, an effect that was not sustained at 2 and 4 weeks. Cocoa-liquor-free CC had no effect, either on endothelial function or on platelet function. Blood pressure and heart rate did not change in either group.ConclusionFlavanol-rich chocolate acutely improves vascular function in patients with CHF. A sustained effect was seen after daily consumption over a 4-week period, even after 12 h abstinence. These beneficial effects were paralleled by an inhibition of platelet function in the presence of FRC only.Trial Registration ClinicalTrials.gov Identifier: NCT00538941.

AIMS: Chronic right ventricular (RV) pacing may impose ventricular dyssynchrony leading to LV remodelling and is associated with increased morbidity and mortality. Upgrading patients with chronic RV pacing to cardiac resynchronization therapy (CRT) may be considered to restore synchronicity and prevent these deleterious effects. METHODS AND RESULTS: A total of 172 patients from two tertiary centres were analysed over a mean follow-up of 21.7 and 23.5 months after primary CRT implantation (n = 102) and CRT upgrade (n = 70), respectively. In the latter group, mean duration of RV pacing before CRT upgrade was 80.3 months, and ventricular stimulation was >95%. A significant improvement in left ventricular (LV) ejection fraction (10 and 11% absolute increase in primary CRT vs. upgrades, respectively), LV end-diastolic diameter index (-0.15 cm/m(2) vs. -0.2 cm/m(2)), and LV end-systolic diameter (-6.0 vs. -7.0 mm) was observed in both groups, which did not differ between primary CRT recipients and CRT upgrades. Response to CRT upgrade was independent of the underlying rhythm, QRS duration, duration of prior RV pacing, or LV function and size at baseline. Of note, even seven of nine patients with RV pacing >12 years responded favourably to CRT. CONCLUSION: The current study demonstrates that CRT reverses LV remodelling in heart failure patients with chronic RV pacing in a similar way as in primary CRT recipients, even after very long periods of RV pacing. Our data, therefore, may have important implications for the treatment of pacemaker-dependent patients with heart failure, and support the use of CRT in this setting.

Resistant hypertension is defined as failure to lower blood pressure to target when a patient adheres to the maximum tolerated doses of three antihypertensive drugs including a diuretic. Notwithstanding the wide availability of several antihypertensive agents and the continued recommendation of dietary and lifestyle modifications, the prevalence of resistant hypertension remains high and is expected to increase thus underscoring the need for potential new treatment modalities in resistant hypertension. Endothelin-1 is a long-lasting potent vasoconstrictor and plays a key role in cardiovascular haemostasis. Endothelin mediates its biological activity in humans through the endothelin A and B receptors. The clinical experience and the evidence for therapy with darusentan in resistant systemic hypertension are reviewed. The leading journals that publish basic science and clinical research in the area of cardiovascular diseases and PubMed were scanned. While results from early clinical studies suggested that darusentan might emerge as new treatment option in patients with resistant hypertension, results from recent studies suggests that darusentan appears unlikely to find its way in the armamentarium for treatment of resistant hypertension.

BACKGROUND: Cyclosporine represents a milestone in immunosuppression following organ transplantation. Its use, however, comes at the cost of significant side effects, such as arterial hypertension which is rarely controllable by currently available anti-hypertensive drugs. The aim was to investigate the effect of acute administration of nitroglycerin in heart-transplanted patients with cyclosporine-induced hypertension. METHODS: The sample included 18 cyclosporine-induced hypertensive patients (HTX group) scheduled for elective cardiac catheterization following heart transplantation, as well as 6-matched essential hypertensive patients (HT group). The blood pressure (BP) in the aorta and pulmonary artery, before and after administration of nitroglycerin, was measured simultaneously. RESULTS: After injection of 50 microg and 100 microg nitroglycerin, BP significantly decreased both in HTX (systolic (s) BP p = 0.0001; diastolic (d) BP p = 0.0001) and in controls (sBP p = 0.006; dBP p = 0.05). This reduction was more pronounced in HTX (sBP p = 0.022; dBP p = 0.018 for group-comparison). Following analysis of the data in relation to its individual baseline, a significantly higher reduction of the BP induced by 100 microg nitroglycerin was observed in the HTX group compared to the HT group (p = 0.02 for sBP and p = 0.03 for dBP). 8 +/- 3 minutes after the last nitrate infusion, BP remained significantly reduced compared to baseline in HTX (p <0.001), whereas it came back to baseline in controls. The reduction in sBP was correlated to cyclosporine A levels (p = 0.04 after 50microg nitroglycerin; p = 0.05 after 100 microg nitroglycerin). CONCLUSION: After application of nitroglycerin, sBP is reduced immediately in HTX with uncontrolled cyclosporine-induced hypertension. Further studies are needed to evaluate the long-term effect of nitrates in these patients.