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Aims: Catheter-based renal nerve ablation (RNA) using radiofrequency energy is a novel treatment for drug-resistant essential hypertension. However, the local endothelial and vascular injury induced by RNA has not been characterized, although this importantly determines the long-term safety of the procedure. Optical coherence tomography (OCT) enables in vivo visualization of morphologic features with a high resolution of 10-15 µm. The objective of this study was to assess the morphological features of the endothelial and vascular injury induced by RNA using OCT., Methods and Results: In a prospective observational study, 32 renal arteries of patients with treatment-resistant hypertension underwent OCT before and after RNA. All pre- and post-procedural OCT pullbacks were evaluated regarding vascular changes such as vasospasm, oedema (notches), dissection, and thrombus formation. Thirty-two renal arteries were evaluated, in which automatic pullbacks were obtained before and after RNA. Vasospasm was observed more often after RNA then before the procedure (0 vs. 42%, P < 0.001). A significant decrease in mean renal artery diameter after RNA was documented both with the EnligHTN (4.69 ± 0.73 vs. 4.21 ± 0.87 mm; P < 0.001) and with the Simplicity catheter (5.04 ± 0.66 vs. 4.57 ± 0.88 mm; P < 0.001). Endothelial-intimal oedema was noted in 96% of cases after RNA. The presence of thrombus formations was significantly higher after the RNA then before ablation (67 vs. 18%, P < 0.001). There was one evidence of arterial dissection after RNA with the Simplicity catheter, while endothelial and intimal disruptions were noted in two patients with the EnligHTN catheter., Conclusion: Here we show that diffuse renal artery constriction and local tissue damage at the ablation site with oedema and thrombus formation occur after RNA and that OCT visualizes vascular lesions not apparent on angiography. This suggests that dual antiplatelet therapy may be required during RNA.

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 ± 5 vs. 95 ± 1%; P = 0.01) and to require heart transplantation (1-year estimated event-free survival: 88 ± 4 vs. 95 ± 1%; P = 0.009). A multivariate Cox proportional hazard model revealed the following independent predictors of mortality: (a) PE (P = 0.04, hazard ratio (HR): 1.95, 95% confidence interval (CI): 1.0-3.7), (b) age (P = 0.04, HR: 1.02, 95% CI: 1.0-1.04) and (c) LVEF <35% (P = 0.03, HR: 1.7, 95% CI: 1.1-2.8)., Conclusion: In chronic heart failure, even minor PEs are associated with an increased risk of all-cause mortality, cardiac death, and need for transplantation.

Aims: Flavanol-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 Results: Twenty 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., Conclusion: Flavanol-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.

The sympathetic nervous system (SNS) plays an important role in the regulation of cardiac performance and peripheral circulation. Changes in SNS activity measured as catecholamines in plasma or organ spillover have been implicated in the pathogenesis of hypertension. Recent studies using microneurography to directly assess peripheral sympathetic nerve activity have demonstrated an increase in sympathetic activity in patients with borderline hypertension at rest and during hypoxia. We have recently shown that resting muscle sympathetic nerve activity is comparable in offspring of hypertensive and normotensive parents. However, during mental arithmetic the increase in muscle sympathetic nerve activity and blood pressure was significantly more pronounced in offspring of hypertensive than in offspring of normotensive parents, but resting blood pressure was in the normotensive range and comparable in both groups. These data indicate that the response to mental stress results in a more pronounced activation of SNS in normotensive subjects with a genetic background of hypertension. In other cardiovascular disease states such as acute myocardial infarction and heart failure activity of the SNS may determine prognosis significantly. Some calcium antagonists which are successfully used to treat patients with hypertension and stable angina pectoris may have unfavourable effects in patients with impaired left ventricular function. This could be due in part to baroreceptor-mediated activation of the SNS, an effect which seems to be related to pharmacokinetics and pharmacodynamics of the drugs. In contrast, angiotensin converting enzyme inhibitors seem to directly decrease sympathetic nerve activity. This may explain at least in part their beneficial effects in patients with impaired left ventricular function. Thus, the SNS as a regulator of the cardiovascular system also plays an important role in the pathophysiology of cardiovascular diseases such as hypertension, myocardial infarction and heart failure. Furthermore, drug therapy could have a significant impact on the activity of the SNS.

The coronary circulation is controlled by the central nervous system, circulating hormones and local vascular mechanisms. The importance of local regulatory mechanisms has only recently been recognized. The endothelium is in a strategical anatomical position within the blood vessel wall located between the circulating blood and vascular smooth muscle cells. It can respond to mechanical and hormonal signals from the blood; of particular importance is the fact that it is a source of mediators which can modulate the contractile state and proliferative responses of vascular smooth muscle cells, platelet function and coagulation as well as monocyte adhesion. Important relaxing factors are nitric oxide and prostacyclin and a putative hyperpolarizing factor. Nitric oxide also inhibits smooth muscle proliferation and, together with prostacyclin, platelet adhesion and aggregation. Bradykinin-induced nitric oxide production is regulated by angiotensin converting enzyme located on the endothelial cell membrane; indeed, the enzyme not only activates angiotensin I into angiotensin II, but also inactivates bradykinin. Endothelin-1 and thromboxane A2 and prostaglandin H2 are contracting factors produced by the endothelium. In contrast to thromboxane A2 and prostaglandin H2 which activate platelets, endothelin has no direct effects on these cells, but has proliferative properties in vascular smooth muscle. Under physiological conditions, the endothelium plays a protective role as it prevents adhesion of circulating blood cells, keeps the vasculature in a vasodilated state and inhibits vascular smooth muscle proliferation. In disease states, however, endothelial dysfunction contributes to enhanced vasoconstrictor responses, adhesion of platelets and monocytes and proliferation of vascular smooth muscle cells, events all known to occur in coronary artery disease. Nitrates substitute in part for deficient endogenous nitric oxide, while angiotensin converting enzyme inhibitors increase the bradykinin induced nitric oxide and prostacyclin production. The newly developed endothelin antagonists allow specific blocking of the effects of endothelin. Pharmacological correction of endothelial dysfunction may be important to treat coronary artery disease and its complications.