Ambulatory prostanoid therapy: safe reduction in duration of inpatient training.

AIMS: IV prostanoid therapy for advanced pulmonary arterial hypertension requires lifelong, continuous infusion, and extensive self-care. The inpatient training pathway (ITP) ensures patient competency but can be psychologically and physically demanding. Therefore, an alternative Elective Prostanoid Admission Pathway (EPAP) was developed.Compare clinical outcomes and patient experiences for patients following the EPAP vs. the ITP. METHODS AND RESULTS: From 2013, clinically stable patients were trained via the EPAP, which consisted of pre-admission including an outpatient training day, followed by inpatient training. The EPAP patients were followed-up face-to-face/via telephone and could access a Clinical Nurse Specialist-led telephone service between appointments. Very high-risk patients were trained via the ITP, which consisted of pre-therapy counselling and daily ward-based training. Prior to 2013, patients followed the ITP pathway irrespective of clinical status. All were enrolled into the 'IV buddy' scheme and retrospectively asked to complete patient experience surveys. Among EPAP (n = 24) and ITP (n = 54) patients, 17% and 33% discontinued therapy, respectively. Among all, frequent challenges to treatment initiation were: dexterity (43%) and body image (27%). Elective Prostanoid Admission Pathway use reduced inpatient stay duration by 8 days per patient and infection rates remained low. Patient experience surveys [n = 17 (EPAP), n = 10 (ITP)] showed equal patient satisfaction between groups, but the incidence of side effects was numerically lower in EPAP patients, who also reported home practice and having access to the 'IV buddy' scheme as 'very useful' [12/14 (86%) and 10/13 (77%), respectively]. CONCLUSIONS: Elective Prostanoid Admission Pathway implementation improved patient outcomes and has the potential for application to other clinical scenarios where patient self-management is required.

Real-time deep artifact suppression using recurrent U-Nets for low-latency cardiac MRI.

PURPOSE: Real-time low latency MRI is performed to guide various cardiac interventions. Real-time acquisitions often require iterative image reconstruction strategies, which lead to long reconstruction times. In this study, we aim to reconstruct highly undersampled radial real-time data with low latency using deep learning. METHODS: A 2D U-Net with convolutional long short-term memory layers is proposed to exploit spatial and preceding temporal information to reconstruct highly accelerated tiny golden radial data with low latency. The network was trained using a dataset of breath-hold CINE data (including 770 time series from 7 different orientations). Synthetic paired data were created by retrospectively undersampling the magnitude images, and the network was trained to recover the target images. In the spirit of interventional imaging, the network was trained and tested for varying acceleration rates and orientations. Data were prospectively acquired and reconstructed in real time in 1 healthy subject interactively and in 3 patients who underwent catheterization. Images were visually compared to sliding window and compressed sensing reconstructions and a conventional Cartesian real-time sequence. RESULTS: The proposed network generalized well to different acceleration rates and unseen orientations for all considered metrics in simulated data (less than 4% reduction in structural similarity index compared to similar acceleration and orientation-specific networks). The proposed reconstruction was demonstrated interactively, successfully depicting catheters in vivo with low latency (39 ms, including 19 ms for deep artifact suppression) and an image quality comparing favorably to other reconstructions. CONCLUSION: Deep artifact suppression was successfully demonstrated in the time-critical application of non-Cartesian real-time interventional cardiac MR.

Neprilysin inhibition for pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled, proof-of-concept trial.

BACKGROUND AND PURPOSE: Pulmonary arterial hypertension (PAH) is an incurable, incapacitating disorder resulting from increased pulmonary vascular resistance, pulmonary arterial remodelling, and right ventricular failure. In preclinical models, the combination of a PDE5 inhibitor (PDE5i) with a neprilysin inhibitor augments natriuretic peptide bioactivity, promotes cGMP signalling, and reverses the structural and haemodynamic deficits that characterize PAH. Herein, we conducted a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of repurposing the neprilysin inhibitor, racecadotril, in PAH. EXPERIMENTAL APPROACH: Twenty-one PAH patients stable on PDE5i therapy were recruited. Acute haemodynamic and biochemical changes following a single dose of racecadotril or matching placebo were determined; this was followed by a 14-day safety and efficacy evaluation. The primary endpoint in both steps was the maximum change in circulating atrial natriuretic peptide (ANP) concentration (Δmax ), with secondary outcomes including pulmonary and systemic haemodynamics plus mechanistic biomarkers. KEY RESULTS: Acute administration of racecadotril (100 mg) resulted in a 79% increase in the plasma ANP concentration and a 106% increase in plasma cGMP levels, with a concomitant 14% fall in pulmonary vascular resistance. Racecadotril (100 mg; t.i.d.) treatment for 14 days resulted in a 19% rise in plasma ANP concentration. Neither acute nor chronic administration of racecadotril resulted in a significant drop in mean arterial BP or any serious adverse effects. CONCLUSIONS AND IMPLICATIONS: This Phase IIa evaluation provides proof-of-principle evidence that neprilysin inhibitors may have therapeutic utility in PAH and warrants a larger scale prospective trial.

The CRASH report: emergency management dilemmas facing acute physicians in patients with pulmonary arterial hypertension.

Treatment of acute emergencies in patients with pulmonary arterial hypertension (PAH) can be challenging. In the UK and Ireland, management of adult patients with PAH is centred in eight nationally designated pulmonary hypertension (PH) centres. However, many patients live far from these centres and physicians in local hospitals are often required to manage PAH emergencies. A committee of physicians from nationally designated PH centres identified the 'most common' emergency clinical scenarios encountered in patients with PAH. Thereafter, a review of the literature was performed centred on these specified topics and a management approach was developed based on best available evidence and expert consensus. Management protocols were developed on the following PAH emergencies: chest pain (including myocardial ischaemia), right ventricular failure, arrhythmias, sepsis, haemoptysis ('CRASH'), as well as considerations relevant to surgery, anaesthesia and pregnancy. Emergencies are not uncommon in PAH. While expertise in PAH management is essential, all physicians involved in acute care should be aware of the principles of acute management of PAH emergencies. A multidisciplinary approach is necessary, with physicians from tertiary PH centres supporting care locally and planning safe transfer of patients to PH centres when appropriate.

Noninvasive pulmonary artery wave intensity analysis in pulmonary hypertension.

Pulmonary wave reflections are a potential hemodynamic biomarker for pulmonary hypertension (PH) and can be analyzed using wave intensity analysis (WIA). In this study we used pulmonary vessel area and flow obtained using cardiac magnetic resonance (CMR) to implement WIA noninvasively. We hypothesized that this method could detect differences in reflections in PH patients compared with healthy controls and could also differentiate certain PH subtypes. Twenty patients with PH (35% CTEPH and 75% female) and 10 healthy controls (60% female) were recruited. Right and left pulmonary artery (LPA and RPA) flow and area curves were acquired using self-gated golden-angle, spiral, phase-contrast CMR with a 10.5-ms temporal resolution. These data were used to perform WIA on patients and controls. The presence of a proximal clot in CTEPH patients was determined from contemporaneous computed tomography/angiographic data. A backwards-traveling compression wave (BCW) was present in both LPA and RPA of all PH patients but was absent in all controls (P = 6e(-8)). The area under the BCW was associated with a sensitivity of 100% [95% confidence interval (CI) 63-100%] and specificity of 91% (95% CI 75-98%) for the presence of a clot in the proximal PAs of patients with CTEPH. In conclusion, WIA metrics were significantly different between patients and controls; in particular, the presence of an early BCW was specifically associated with PH. The magnitude of the area under the BCW showed discriminatory capacity for the presence of proximal PA clot in patients with CTEPH. We believe that these results demonstrate that WIA could be used in the noninvasive assessment of PH.