23 September 2022

This week in PVD

Pulmonary artery denervation improves exercise capacity in group 1 PAH

BOSTON — Pulmonary artery denervation improved exercise capacity and measures of cardiac function vs. a sham procedure in patients with WHO group 1 pulmonary arterial hypertension, speaker reported.

The results of the PADN-CFDA trial were presented at TCT 2022 and simultaneously published in JACC: Cardiovascular Interventions.

“From 2012, our team and other teams have provided some data to support the treatment effect of [pulmonary artery denervation] for treatment of group 1 pulmonary arterial hypertension, which is a progressive, incurable disease, but the treatment effect of PADN for group 1 has not been studied in randomization,” Shao-Liang Chen, MD, fellow at the Collaborative Innovation Center for Cardiovascular Disease Translational Medicine at Nanjing Medical University in Nanjing, China, said during a press conference.

Chen and colleagues conducted a sham-controlled randomized trial to evaluate the effects of pulmonary artery denervation in 128 patients with group 1 pulmonary hypertension. For trial inclusion, patients were free from exposure to pulmonary arterial hypertension-specific drugs for 30 days prior to enrollment.

Metabolites can help identify PAH linked to systemic sclerosis: Study

A new study has found that there are nine metabolites — molecules that take part in metabolism — in the blood that can tell pulmonary arterial hypertension (PAH) linked to systemic sclerosis from idiopathic PAH, the label given when the disease is due to an unknown cause.

Researchers also observed that some of these metabolites were associated with worse disease in patients with PAH tied to systemic sclerosis.

These findings “offer a more comprehensive metabolic guide to much needed diagnostic, prognostic, and therapeutic strategies of precision medicine” in patients with systemic sclerosis-PAH (or SSc-PAH), the researchers wrote.

“SSc-PAH is characterized by significant metabolomic alterations that associate with markers of disease severity which may explain accelerated disease course and contribute to poor response to therapy compared to IPAH,” the team wrote.

The study, “Metabolomic profiles differentiate scleroderma-PAH from idiopathic PAH and correspond with worsened functional capacity,” was published in the journal Chest.

Bruton’s tyrosine kinase could be a potential therapeutic target for PAH

Researchers from China showed that inhibition of Bruton’s tyrosine kinase (BTK) improved pulmonary arterial hypertension (PAH), pulmonary vascular remodeling, and right ventricle hypertrophy in a rodent model of PAH. Moreover, it alleviated pulmonary vascular fibrosis and decreased endothelial-to-mesenchymal transition (EndMT).

“These beneficial effects of BTK inhibition are associated with the suppression of [nucleotide-binding oligomerization domain-like receptor with pyrin domain 3] inflammasome and NF-κB/MAPK signaling, thereafter reduce M1 macrophage polarization and M1-related inflammatory cytokine production, and thereafter, alleviate EndMT and pulmonary vascular remodeling,” the researchers explained.

Yu et al used the compound BGB-3111 to selectively inhibit BTK. Intragastric administration of BGB-3111 suppressed monocrotaline (MCT)-induced increase of perivascular macrophages and recruitment of polarized M1 macrophages (inflammatory), but not M2 macrophages (immunosuppressive), to the bronchoalveolar lavage fluid. Changes in macrophage polarization phenotype (M1/M2) have been implicated in the development and progression of PAH.

Eteplirsen delays pulmonary decline in duchenne muscular dystrophy

In patients with Duchenne muscular dystrophy (DMD), treatment with eteplirsen — a type of antisense oligonucleotide that promotes dystrophin production by restoring the translation reading frame of the DMD gene — is associated with statistically significant, clinically meaningful attenuation in the percentage of predicted forced vital capacity (FVC%p).

Recognizing that pulmonary decline is a major issue in individuals with DMD, researchers sought to evaluate the effect of eteplirsen treatment, as derived from newly available data sources, on pulmonary function over time in patients with DMD.

In this post hoc analysis, researchers compared the FVC%p and projected time with pulmonary function milestones in patients with DMD and exon 51 skip-amenable mutations being treated with eteplirsen. Overall, 113 participants fulfilled the inclusion criteria and were included in the main analysis. Of the patients treated with eteplirsen, 20 were enrolled in Study 204 (ClinicalTrials.gov Identifier: NCT02286947) and 52 were enrolled in Study 301 (ClinicalTrials.gov Identifier: NCT02255552). Of the patients who received standard of care (SoC), 20 were enrolled in Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG-DNHS; ClinicalTrials.gov Identifier: NCT00468832) and 21 were enrolled in DEMAND III (ClinicalTrials.gov identifier: NCT01254019).

Bioinformatics analysis reveals new potential therapeutic targets in PAH

A new bioinformatics study offers insight into the pathogenesis of pulmonary arterial hypertension (PAH) as well as 10 newly identified hub genes that could represent potential treatment targets for the disease. The study, published in the Canadian Respiratory Journal, employed multiple microarray analyses to provide a theoretical basis for future research in PAH.

“Although basic discoveries and pivotal clinical trials have led to the development of medications in recent years, patients with PAH still have a poor prognosis,” the authors wrote. “The objective of this study was to use transcriptomic microarray data analysis to find genes associated with the onset of pulmonary hypertension, and to provide a research basis for identifying new potential therapeutic targets.”

The research team used bioinformatics analyses of 2 sets of microarray data from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus, an open-access database, to search for differentially expressed genes (DEGs) between patients with PAH and healthy controls as well as for the primary signaling pathways of those genes.

Grant helps eko develop al algorithm for detecting PH

Digital health company Eko has been awarded $2.7 million from the National Institutes of Health (NIH) to develop an artificial intelligence (AI)-based algorithm that can detect pulmonary hypertension (PH) and classify its severity.

The algorithm will analyze data from two common, noninvasive heart tests collected via Eko’s digital smart stethoscopes. Machine learning, a type of AI that learns how to predict outcomes by analyzing large amounts of data, will be used to translate data from these heart tests into meaningful predictions.

Eko hopes the new identification tool will enable PH to be diagnosed sooner and more accurately, allowing patients earlier access to life-saving treatments compared with existing diagnostic tools.

“This machine learning algorithm has the potential to be a low cost, easily implementable, and sustainable medical technology that assists healthcare professionals in identifying more patients with pulmonary hypertension,” Gaurav Choudhary, MD, said in a press release. Choudhary is principal investigator and director of cardiovascular research at the Lifespan Cardiovascular Institute in Rhode Island. He also is director of cardiovascular research at the Alpert Medical School of Brown University.

Global COPD prevalence, deaths and disability-adjusted life-years declined in recent years

COPD prevalence, death and disability-adjusted life-year rates around the world were lower in 2019 than in 1990, researchers reported in The BMJ.

Researchers conducted a systematic analysis of data from the Global Burden of Disease Study 2019 for 204 countries and territories between 1990 and 2019. Researchers assessed data on the prevalence, deaths and disability-adjusted life-years (DALYs) of COPD and possible attributable risk factors.

Of the 212.3 million prevalent COPD cases reported globally in 2019, COPD accounted for 3.3 million deaths and 74.4 million DALYs. The global age-standardized point prevalence for COPD was 2,638.2 per 100,000 population, death rate was 42.5 and DALY rate was 926.1. These rates were 8.7%, 41.7% and 39.8% lower than those reported in 1990, respectively.

In 2019, the highest age-standardized point prevalence for COPD was in Denmark (4,299.5 per 100,000 population), followed by Myanmar (3,963.7 per 100,000 population) and Belgium (3,927.7 per 100,000 population). Egypt, Georgia and Nicaragua had the largest increases in age-standardized point prevalence for COPD from 1990 to 2019, at 62%, 54.9% and 51.6%, respectively.

Pulnovo’s PADN device yields improved outcomes in PAH trial

Treatment with Pulnovo Medical‘s pulmonary artery denervation (PADN) device improved exercise capacity, blood flow dynamics, and clinical outcomes for pulmonary arterial hypertension (PAH) patients in a clinical trial called PADN-CFDA, the company announced.

“The PADN-CFDA results are very important because this was an adequately powered randomized controlled trial, and what we clearly saw was that there was lower rates of clinical worsening and a better satisfactory clinical response,” Gregg Stone, MD, a member of the Pulnovo’s scientific advisory board, said in a press release. Stone is chairman of the steering committee for an upcoming global clinical trial to test the PADN device.

Results from the trial were presented at this year’s Transcatheter Cardiovascular Therapy conference (TCT 2022). A study detailing the findings has been accepted for publication in JACC: Cardiovascular Interventions.

Pulnovo’s PADN device uses radio waves to block nerve activity around the pulmonary artery, the main blood vessel connecting the heart to the lungs. By blocking these nerves, blood pressure drops in the pulmonary artery, ultimately slowing disease progression. The device consists of a special looped catheter that’s inserted through a large blood vessel in the leg.

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