Remote exercise testing in pulmonary hypertension (PHRET)

Remote exercise tests for patients with pulmonary hypertension (PH) would improve the telemedicine strategies in this disease. The PHRET study assessed the validity and feasibility of four remote exercise tests performed by PH patients at home. Participants undergoing diagnostic assessment for PH were included. At baseline, patients completed a 6MWT followed by a range of study tests including a Timed Up and Go (TUG) test, a Sit-to-Stand (STS), a Step Test (ST), and a tele-6MWT (T6MWT) performed outside using a GPS-enabled smartphone. Patients performed these tests at home following discharge and at first follow-up. Analysis focused on comparing the results of study tests to the standard 6MWT. The discontinuation rate was 15%. Ninety-seven percent of patients were able to complete a TUG, 92% a STS, 73% a ST, and 49% a T6MWT. At baseline, correlation between the standard 6MWT and study tests, respectively, was T6MWT 0.93, ST 0.78, STS 0.71, and TUG −0.76 (p < 0.001). Direction of change in the study test agreed with the standard 6MWT in 68% of the follow-up ST, 68% of the STS, 71% of the TUG, and 79% of the T6MWT. Patients were able to complete the tests at home, there were no adverse incidents and ≥92% of patients were happy to continue performing home tests. Remote exercise testing is feasible. The T6MWT was a valid remote measure of exercise capacity, but could only be performed by a limited number of patients. The high discontinuation rate may impact the utility of remote tests

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

The right ventricle under pressure: anatomy and imaging in sickness and health

The right ventricle (RV) is an important structure which serves a multitude of vital physiological functions in health. For many years, the left ventricle has dominated the focus of understanding in both biology and pathophysiology and the RV was felt to be more of a passive structure which rarely had an effect on disease states. However, it is increasingly recognised that the RV is essential to the homoeostasis of normal physiology and disturbances in RV structure and function have a substantial effect on patient outcomes. Indeed, the prognosis of diseases of lung diseases affecting the pulmonary vasculature and left heart disease is intimately linked to the function of the right ventricle. This review sets out to describe the developmental and anatomical complexities of the right ventricle while exploring the modern techniques employed to image and understand its function from a clinical perspective

COMPERA 2.0 risk stratification in medically managed chronic thromboembolic pulmonary hypertension

The newly proposed COMPERA 2.0 risk stratification model provides improved clinical refinement and is applicable in medically managed chronic thromboembolic pulmonary hypertension (CTEPH)

Remote exercise testing in pulmonary hypertension (PHRET)

Abstract Remote exercise tests for patients with pulmonary hypertension (PH) would improve the telemedicine strategies in this disease. The PHRET study assessed the validity and feasibility of four remote exercise tests performed by PH patients at home. Participants undergoing diagnostic assessment for PH were included. At baseline, patients completed a 6MWT followed by a range of study tests including a Timed Up and Go (TUG) test, a Sit‐to‐Stand (STS), a Step Test (ST), and a tele‐6MWT (T6MWT) performed outside using a GPS‐enabled smartphone. Patients performed these tests at home following discharge and at first follow‐up. Analysis focused on comparing the results of study tests to the standard 6MWT. The discontinuation rate was 15%. Ninety‐seven percent of patients were able to complete a TUG, 92% a STS, 73% a ST, and 49% a T6MWT. At baseline, correlation between the standard 6MWT and study tests, respectively, was T6MWT 0.93, ST 0.78, STS 0.71, and TUG −0.76 (p < 0.001). Direction of change in the study test agreed with the standard 6MWT in 68% of the follow‐up ST, 68% of the STS, 71% of the TUG, and 79% of the T6MWT. Patients were able to complete the tests at home, there were no adverse incidents and ≥92% of patients were happy to continue performing home tests. Remote exercise testing is feasible. The T6MWT was a valid remote measure of exercise capacity, but could only be performed by a limited number of patients. The high discontinuation rate may impact the utility of remote tests

Remote-management of COPD: Evaluating the Implementation of Digital Innovation to Enable Routine Care (RECEIVER): the protocol for a feasibility and service adoption observational cohort study

Introduction: Reductions in exacerbation and hospitalisations are the outcomes rated as most important by people with chronic obstructive pulmonary disease (COPD). Most COPD management is currently based on a reactive approach, and delays in recognising treatable opportunities underpin COPD care quality gaps. Innovations that empower COPD self-management, facilitate integrated clinical care and support delivery of evidence-based treatment interventions are urgently required. Methods and analysis: The Remote-Management of COPD: Evaluating the Implementation of Digital Innovation to Enable Routine Care trial is a prospective observational cohort hybrid implementation and effectiveness study that will explore the adoption of a digital service model for people with ‘high-risk’ COPD and evaluate the feasibility of this approach versus current standards of care. People with COPD, who have had recent severe exacerbation and/or COPD–obstructive sleep apnoea overlap or chronic hypercapnic respiratory failure requiring home non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP), with internet access will be recruited into the study and enrolled into the digital service. Study endpoints will examine participant utilisation, clinical service impact and clinical outcomes compared with historical and contemporary control patient data. The digital infrastructure will also provide a foundation to explore the feasibility of approaches to predict outcomes and exacerbation in people with COPD through machine learning analysis. Ethics and dissemination: Ethical approval for this clinical trial has been obtained from the West of Scotland Research Ethics Service. The trial will commence in September 2019 for a duration of 2 years. Results will be presented at local, national and international meetings, as well as submission for publication to peer-reviewed journals. Trial registration number: NCT04240353

A randomised controlled trial of non-invasive ventilation compared with extracorporeal carbon dioxide removal for acute hypercapnic exacerbations of chronic obstructive pulmonary disease

BACKGROUND: Patients presenting with acute hypercapnic respiratory failure due to exacerbations of chronic obstructive pulmonary disease (AECOPD) are typically managed with non-invasive ventilation (NIV). The impact of low-flow extracorporeal carbon dioxide removal (ECCO(2)R) on outcome in these patients has not been explored in randomised trials. METHODS: Open-label randomised trial comparing NIV (NIV arm) with ECCO(2)R (ECCO(2)R arm) in patients with AECOPD at high risk of NIV failure (pH < 7.30 after ≥ 1 h of NIV). The primary endpoint was time to cessation of NIV. Secondary outcomes included device tolerance and complications, changes in arterial blood gases, hospital survival. RESULTS: Eighteen patients (median age 67.5, IQR (61.5–71) years; median GOLD stage 3 were enrolled (nine in each arm). Time to NIV discontinuation was shorter with ECCO(2)R (7:00 (6:18–8:30) vs 24:30 (18:15–49:45) h, p = 0.004). Arterial pH was higher with ECCO(2)R at 4 h post-randomisation (7.35 (7.31–7.37) vs 7.25 (7.21–7.26), p < 0.001). Partial pressure of arterial CO(2) (PaCO(2)) was significantly lower with ECCO(2)R at 4 h (6.8 (6.2–7.15) vs 8.3 (7.74–9.3) kPa; p = 0.024). Dyspnoea and comfort both rapidly improved with commencement of ECCO(2)R. There were no severe or life-threatening complications in the study population. There were no episodes of major bleeding or red blood cell transfusion in either group. ICU and hospital length of stay were longer with ECCO(2)R, and there was no difference in 90-day mortality or functional outcomes at follow-up. INTERPRETATION: There is evidence of benefit associated with ECCO(2)R with time to improvement in respiratory acidosis, in respiratory physiology and an immediate improvement in patient comfort and dyspnoea with commencement of ECCO(2)R. In addition, there was minimal clinically significant adverse events associated with ECCO(2)R use in patients with AECOPD at risk of failing or not tolerating NIV. However, the ICU and hospital lengths of stay were longer in the ECCO(2)R for similar outcomes. Trial registration The trial is prospectively registered on ClinicalTrials.gov: NCT02086084. Registered on 13th March 2014, https://clinicaltrials.gov/ct2/show/NCT02086084?cond=ecco2r&draw=2&rank=8 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13613-022-01006-8

Long-term usage and improved clinical outcomes with adoption of a COPD digital support service: key findings from the RECEIVER trial

Purpose: Digital tools may improve chronic obstructive pulmonary disease (COPD) management, but further evidence of significant, persisting benefits are required. The RECEIVER trial was devised to evaluate the Lenus COPD support service by determining if people with severe COPD would continue to utilize the co-designed patient web application throughout study follow-up and to explore the impact of this digital service on clinical outcomes with its adoption alongside routine care. Patients and Methods: The prospective observational cohort hybrid implementation-effectiveness study began in September 2019 and included 83 participants. Recruitment stopped in March 2020 due to COVID-19, but follow-up continued as planned. A contemporary matched control cohort was identified to compare participant clinical outcomes with and minimize biases associated with wider COVID-19 impacts. Utilization was determined by daily COPD assessment test (CAT) completion through the application. Survival metrics and post-index date changes in annual hospitalizations were compared between the RECEIVER and control cohorts. Longitudinal quality of life and symptom burden data and community-managed exacerbation events were also captured through the application. Results: High and sustained application utilization was noted across the RECEIVER cohort with a mean follow-up of 78 weeks (64/83 participants completed at least one CAT entry on ≥ 50% of possible follow-up weeks). Subgroup analysis of participants resident in more socioeconomically deprived postcode areas revealed equivalent utilization. Median time to death or a COPD or respiratory-related admission was higher in the RECEIVER cohort compared to control (335 days vs 155 days). Mean reduction in annual occupied bed days was 8.12 days vs 3.38 days in the control cohort. Quality of life and symptom burden remained stable despite the progressive nature of COPD. Conclusion: The sustained utilization of the co-designed patient application and improvements in participant outcomes observed in the RECEIVER trial support scale-up implementation with continued evaluation of this digital service