Rationale and design of the PHOspholamban RElated CArdiomyopathy intervention STudy (i-PHORECAST).

BACKGROUND: The p.Arg14del (c.40_42delAGA) phospholamban (PLN) pathogenic variant is a founder mutation that causes dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM). Carriers are at increased risk of malignant ventricular arrhythmias and heart failure, which has been ascribed to cardiac fibrosis. Importantly, cardiac fibrosis appears to be an early feature of the disease, occurring in many presymptomatic carriers before the onset of overt disease. As with most monogenic cardiomyopathies, no evidence-based treatment is available for presymptomatic carriers. AIMS: The PHOspholamban RElated CArdiomyopathy intervention STudy (iPHORECAST) is designed to demonstrate that pre-emptive treatment of presymptomatic PLN p.Arg14del carriers using eplerenone, a mineralocorticoid receptor antagonist with established antifibrotic effects, can reduce disease progression and postpone the onset of overt disease. METHODS: iPHORECAST has a multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) design. Presymptomatic PLN p.Arg14del carriers are randomised to receive either 50 mg eplerenone once daily or no treatment. The primary endpoint of the study is a multiparametric assessment of disease progression including cardiac magnetic resonance parameters (left and right ventricular volumes, systolic function and fibrosis), electrocardiographic parameters (QRS voltage, ventricular ectopy), signs and/or symptoms related to DCM and ACM, and cardiovascular death. The follow-up duration is set at 3 years. BASELINE RESULTS: A total of 84 presymptomatic PLN p.Arg14del carriers (n = 42 per group) were included. By design, at baseline, all participants were in New York Heart Association (NHYA) class I and had a left ventricular ejection fraction > 45% and < 2500 ventricular premature contractions during 24-hour Holter monitoring. There were no statistically significant differences between the two groups in any of the baseline characteristics. The study is currently well underway, with the last participants expected to finish in 2021. CONCLUSION: iPHORECAST is a multicentre, prospective randomised controlled trial designed to address whether pre-emptive treatment of PLN p.Arg14del carriers with eplerenone can prevent or delay the onset of cardiomyopathy. iPHORECAST has been registered in the clinicaltrials.gov-register (number: NCT01857856).

Splenic rupture following colonoscopy, a rare complication.

Splenic rupture is an extremely rare complication of colonoscopy. So far, less than 80 cases have been reported worldwide since 1970. We report two patients, one patient presenting with haemorrhagic shock after a therapeutic colonoscopy and another patient presenting with abdominal pain following a diagnostic colonoscopy. In both cases splenic rupture was diagnosed by abdominal computed tomography (CT scan). One patient was treated by selective embolisation of the splenic artery; the other patient underwent a splenectomy. Because the numbers of colonoscopies performed in The Netherlands as well as in many other European countries are likely to double in the coming years as a result of the introduction of nationwide colorectal cancer screening programmes and intensive surveillance protocols after polypectomy, more splenic injuries as a complication of colonoscopy can be expected in the near future. Awareness of this complication is of great importance in early recognition and management of this potentially life-threatening injury.

Guidelines for heart transplantation.

Based on the changes in the field of heart transplantation and the treatment and prognosis of patients with heart failure, these updated guidelines were composed by a committee under the supervision of both the Netherlands Society of Cardiology and the Netherlands Association for Cardiothoracic surgery (NVVC and NVT).THE INDICATION FOR HEART TRANSPLANTATION IS DEFINED AS: 'End-stage heart disease not remediable by more conservative measures'.CONTRAINDICATIONS ARE: irreversible pulmonary hypertension/elevated pulmonary vascular resistance; active systemic infection; active malignancy or history of malignancy with probability of recurrence; inability to comply with complex medical regimen; severe peripheral or cerebrovascular disease and irreversible dysfunction of another organ, including diseases that may limit prognosis after heart transplantation.Considering the difficulties in defining end-stage heart failure, estimating prognosis in the individual patient and the continuing evolution of available therapies, the present criteria are broadly defined. The final acceptance is done by the transplant team which has extensive knowledge of the treatment of patients with advanced heart failure on the one hand and thorough experience with heart transplantation and mechanical circulatory support on the other hand. (Neth Heart J 2008;16:79-87.).

Is topical local anaesthesia necessary when performing paediatric flexible nasendoscopy? A double-blind randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of lignocain 2% and oxymetazoline 0.025% compared to oxymetazoline 0.025% alone when administered prior to fibreoptic nasendoscopy in paediatric patients. STUDY DESIGN: Prospective, randomized controlled, double-blind study. A group of 56 children, undergoing nasendoscopy to determine adenoidal size, were randomized into two groups and received either lignocain 2% and oxymetazoline 0.025% or oxymetazoline 0.025% alone prior to fibreoptic nasendoscopy. SETTING: A tertiary care Paediatric Hospital. METHOD: The endoscopist recorded the ease of performance of the procedure, cooperation of patient and quality of the view achieved using a visual analogue scale (VAS). The pain and anxiety levels of the child were recorded before, during and immediately after the procedure, using a VAS. The duration of performing the procedure was recorded from insertion of the endoscope into the nostril until removal. RESULTS: All 56 children were able to undergo the endoscopy and the full anxiety and pain assessment was done. Three children were excluded because they have undergone nasendoscopies before. Of the 53 patients included, 27 children received solution A (oxymetazoline 0.025%) and 26 children received solution B (oxymetazoline 0.025% and lignocain 2%). There was no statistical difference between the two groups regarding the duration of the endoscopy, quality of view, ease of performance and cooperation of the patients. The median pain and anxiety scores were not significantly different between the two groups. CONCLUSIONS: This study concludes that the use of a decongestant (oxymetazoline) for paediatric nasendoscopy is just as effective as the use of oxymetazoline with lignocain. Pain and anxiety is not increased in the absence of lignocain.

Early and late arterial healing response to catheter-induced laser, thermal, and mechanical wall damage in the rabbit.

Pulsed lasers are being promoted for laser angioplasty because of their capacity to ablate obstructions without producing adjacent thermal tissue injury. The implicit assumption that thermal injury to the artery is to be avoided was tested. Thermal lesions were produced in the iliac arteries and aorta of normal rabbits by a) electrical spark erosion, b) the metal laser probe, and c) continuous wave neodymium-yttrium aluminum garnet (Nd-YAG) laser energy through the sapphire contact probe. High-energy doses were used to induce substantial damage without perforating the vessel wall. Thermal lesions (n = 77) were compared with mechanical lesions (n = 22) induced by oversized balloon dilation. Medial necrosis was induced by all four injury methods. Provided no extravascular contrast was observed after the injury, all damaged segments were patent after 1 to 56 days. The progression of healing with myointimal proliferation was remarkably similar for all injuries. At 56 days, the neointima measured up to 370 microns. In conclusion, provided no perforation with contrast extravasation occurred, the normal rabbit artery recovered well from transmural thermal injury. The wall healing response is largely nonspecific.