Safety, Tolerability and Clinical Effects of a Rapid Dose Titration of Subcutaneous Treprostinil Therapy in Pulmonary Arterial Hypertension: A Prospective Multi-Centre Trial.

BACKGROUND: Subcutaneous treprostinil has dose-dependent beneficial effects in patients with severe pulmonary arterial hypertension, but adverse effects like infusion site pain can lead to treatment discontinuation. OBJECTIVES: The objective of this study was to evaluate safety, tolerability and clinical effects of a rapid up-titration dosing regimen of subcutaneous treprostinil using proactive infusion site pain management. METHODS: Effects of rapid up-titration dosing regimen on tolerability and clinical parameters were evaluated in this 16-week, open-label multi-centre study. RESULTS: Thirty-nine patients with idiopathic or heritable pulmonary arterial hypertension on stable treatment with oral pulmonary arterial hypertension-approved drugs (90% on dual combination therapy) were included. Patients achieved a median treprostinil dosage of 35.7 ng/kg/min after 16 weeks. A good overall safety profile was demonstrated with 3 patients (8%) withdrawing due to infusion site pain, which occurred in 97% of patients. After 16 weeks, median 6-min walking distance, cardiac index, pulmonary vascular resistance, and tricuspid annular plane systolic excursion improved. CONCLUSIONS: Rapid up-titration of subcutaneous treprostinil was well tolerated, achieving a clinically effective dose associated with improvement of exercise capacity and haemodynamics after 16 weeks. A rapid dose titration regimen and proactive infusion site pain management may improve the handling of this therapy and contribute to better treatment outcome.

Applicability of cardiogoniometry as a non-invasive screening tool for the detection of graft vasculopathy in heart transplant recipients.

Currently available diagnostic modalities for the detection of graft vasculopathy following orthotopic heart transplantation are subject to various restrictions. We hypothesized that cardiogoniometry, a novel non-invasive diagnostic tool for the detection of atherosclerotic coronary vessel disease, is applicable in the graft vasculopathy setting. Cardiogoniometric results were obtained during routine follow-up in 49 consecutive, unselected heart transplant recipients and then retrospectively correlated blindly by an independent reader to recent angiographic findings. Sensitivity of cardiogoniometry was 100%, specificity 62.3%, positive predictive value 68.75%, negative predictive value 100%, negative likelihood ratio 0 and positive likelihood ratio 2.888. Cardiogoniometry is potentially applicable as an easy-to-perform, non-invasive screening tool predominantly for the exclusion but also for the detection of graft vasculopathy in heart transplant recipients.

Late enhancement: a new feature in MRI of arrhythmogenic right ventricular cardiomyopathy?

Aim of the study was to evaluate whether late enhancement (LE) in contrast-enhanced MRI can be used to characterize fibrofatty myocardial replacement in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC). Fifteen patients with suspected ARVC underwent CE-MRI using a 1.5 T scanner. Long and short axis SSFP cine images and T1-weighted fast spin echo images were collected in all patients. After injection of 0.2 mmol/kg Gd-DTPA (Magnevist, Schering, Berlin, Germany), inversion recovery gradient echo images were acquired in long and contiguous short axes to detect myocardial LE indicating areas of fibrous tissue within the myocardium. For definition of ARVC, the ESC Task force criteria were used. In 7 (47%) of 15 patients, ARVC was diagnosed based on the ESC criteria. In all of these 7 patients, MRI showed morphologic or functional criteria of ARVC according to the ESC. LE of the right ventricular myocardium was detected in 5 (71%) of the 7 ARVC patients, additional LE of the left ventricular myocardium in 2 of these patients. None of the 7 patients meeting the ARVC diagnostic criteria had fatty RV infiltration demonstrable by conventional T1-weighted imaging. Eight patients neither showed morphologic criteria of ARVC nor LE. In conclusion, late enhancement can be detected in the right and left ventricular myocardium in some ARVC patients. LE might represent intramyocardial areas of fibrous tissue.