AimIncreasing evidence suggests an important role for hyperactivation of the sympathetic nervous system (SNS) in the clinical phenomena of heart failure with normal LVEF (HFNEF) and hypertension. Moreover, the level of renal sympathetic activation is directly related to the severity of heart failure. Since percutaneous renal denervation (pRDN) has been shown to be effective in modulating elevated SNS activity in patients with hypertension, it can be hypothesized that pRDN has a positive effect on HFNEF. The DIASTOLE trial will investigate whether renal sympathetic denervation influences parameters of HFNEF. MethodsDIASTOLE is a multicentre, randomized controlled trial. Sixty patients, diagnosed with HFNEF and treated for hypertension, will be randomly allocated in a 1:1 ratio to undergo renal denervation on top of medical treatment (n ¼ 30) or to maintain medical treatment alone (n ¼ 30). The primary objective is to investigate the efficacy of pRDN by means of pulsed wave Doppler echocardiographic parameters. Secondary objectives include safety of pRDN and a comparison of changes in the following parameters after pRDN: LV mass, LV volume, LVEF, and left atrial volume as determined by magnetic resonance imaging. Also, MIBG (metaiodobenzylguanidine) uptake and washout, BNP levels, blood pressure, heart rate variability, exercise capacity, and quality of life will be assessed.Perspective DIASTOLE is a randomized controlled trial evaluating renal denervation as a treatment option for HFNEF. The results of the current trial will provide important information regarding the treatment of HFNEF, and therefore may have major impact on future therapeutic strategies. Trail registration NCT01583881--

Exenatide did not reduce myocardial infarct size expressed as a percentage of AAR in ST elevated myocardial infarction patients successfully treated with percutaneous coronary intervention.

Purpose Complex high-risk percutaneous coronary intervention (PCI) is challenging and frequently accompanied by haemodynamic instability. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide cardiopulmonary support in highrisk PCI. However, the outcome is unclear. Methods A two-centre, retrospective study was performed of all patients undergoing high-risk PCI and receiving VA-ECMO for cardiopulmonary support. Results A total of 14 patients (92% male, median age 69 (53-83) years), of whom 50% had previous coronary artery disease in the form of a coronary artery bypass graft (36%) and a PCI (14%) underwent highrisk PCI and received VA-ECMO support. The main target lesion was a left main coronary artery in 78%, a left anterior descending artery in 14%, a right coronary artery in 7%, and 71% underwent multi-vessel PCI in addition to main target vessel PCI. The median SYNTAX score was 27.2 (8-42.5) and in 64% (9/14) there was a chronic total occlusion. Left ventricular function was mildly impaired in 7% (1/14), moderately impaired in 14% (2/14) and severely impaired in F. S. van den Brink () • S.

Angiotensin II (Ang II) causes facilitation of sympathetic neurotransmission via prejunctionallylocated AT 1 -receptors. The pithed rat is a suitable model to study the interactions between endogenously produced Ang II and the sympathetic nervous system at the peripheral level. Previously, we demonstrated that inhibition of the facilitatory actions of Ang II is a class effect of all AT 1 -receptor blockers (ARB). However, all ARBs caused less than maximal inhibition after the highest dose, thus causing a U-shaped dose-response curve with respect to sympatho-inhibition. In the present study, we investigated whether the AT 2 -receptor is involved in this 'upturn' of the dose-response relationship. Accordingly, we studied the effect of the ARB, irbesartan (1-60 mg/kg), on the sequelae of electric stimulation of the thoraco-lumbar sympathetic outflow in the presence and absence of the AT 2 -blocker, PD 123319 (0.5 mg/kg +50 µg/kg/min). Additionally, the effect of the combined (nonselective) AT 1 /AT 2 -receptor antagonist saralasin (0.001, 0.003, 0.01 or 0.03 mg/kg/min), on stimulation-induced responses was studied. In addition, we measured PRA-levels after administration of irbesartan, in this model.The stimulation-induced increase in diastolic blood pressure (DBP) could be dose-dependently reduced by irbesartan. Co-infusion with PD 123319 increased the sympatho-inhibitory potency of irbesartan, possibly through displacement of irbesartan from plasma protein binding sites. The U-shaped dose-response relationship observed with irbesartan, which is illustrative for other ARBs in this model, was not observed when PD 123319 was co-administered with irbesartan, nor with the non-selective AT 1 /AT 2 -blocker, saralasin. PRA-levels increased from 111.0+17.8 to 198.7+22.2 ng/ml/hour after administration of irbesartan. PRA-levels did not differ when measured after the three highest doses of irbesartan. ConclusionsThe present findings indicate a facilitatory role for the AT 2 -receptor, which is unmasked by the highest dose of irbesartan. Different plasma Ang II-levels are unlikely to have caused the less than maximal inhibition after the highest dose of irbesartan.