Mayo Clinic Laboratory and pathology research roundup: April 12
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The research roundup provides an overview of the past week’s research from Mayo Clinic Laboratories consultants, including featured abstracts and a complete list of published studies and reviews.
Featured Abstract
Latent pulmonary vascular disease may alter the response to therapeutic atrial shunt device in heart failure.
In the REDUCE LAP-HF II trial, implantation of an atrial shunt device did not provide, overall, clinical benefit for patients with heart failure and preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). However, pre-specified analyses identified differences in response in subgroups defined by pulmonary artery systolic pressure during submaximal exercise, right atrial (RA) volume, and sex. Shunt implantation reduces left atrial (LA) pressures but increases pulmonary blood flow, which may be poorly tolerated in patients with pulmonary vascular disease (PVD). Based upon these results, we hypothesized that patients with latent PVD, defined as elevated pulmonary vascular resistance (PVR) during exercise, might be harmed by shunt implantation, and conversely that patients without PVD might benefit. Methods: REDUCE LAP-HF II enrolled 626 patients with HF, EF ≥40%, exercise pulmonary capillary wedge pressure ≥25 mmHg, and resting PVR <3.5 WU who were randomized 1:1 to atrial shunt device or sham control. The primary outcome, a hierarchical composite of cardiovascular death, nonfatal ischemic stroke, recurrent HF events, and change in health status, was analyzed using the win ratio. Latent PVD was defined as PVR ≥1.74 WU (highest tertile) at peak exercise, measured prior to randomization. Results: Compared to patients without PVD (n=382), those with latent PVD (n=188) were older, had more atrial fibrillation and right heart dysfunction, and were more likely to have elevated LA pressure at rest. Shunt treatment was associated with worse outcomes in patients with PVD (win ratio 0.60, [95% CI 0.42, 0.86]; p=0.005) and signal of clinical benefit in patients without PVD (win ratio 1.31 [95% CI 1.02, 1.68]; p=0.038). Patients with larger RA volumes and men had worse outcomes with the device, and both groups were more likely to have pacemakers, HFmrEF, and increased LA volume. For patients without latent PVD or pacemaker (n=313, 50% of randomized patients), shunt treatment resulted in more robust signal of clinical benefit (win ratio 1.51 [95% CI 1.14, 2.00]; p=0.004). Conclusions: In patients with HFpEF/HFmrEF, the presence of latent PVD uncovered by invasive hemodynamic exercise testing identifies patients who may worsen with atrial shunt therapy, whereas those without latent PVD may benefit.
Published to PubMed This Week
- MTAP deficiency creates an exploitable target for antifolate therapy in 9p21-loss cancers.
Nature Communications - Dynamics of plasmid-mediated niche invasion, immunity to invasion, and pheromone-inducible conjugation in the murine gastrointestinal tract.
Nature Communications - Cytogenetic abnormalities in essential thrombocythemia: Clinical and molecular correlates and prognostic relevance in 809 informative cases.
Blood Cancer Journal - Cytogenetic abnormalities in essential thrombocythemia: Clinical and molecular correlates and prognostic relevance in 809 informative cases.
Blood Cancer Journal - Targeted metagenomic sequencing-based approach applied to 2,146 tissue and body fluid samples in routine clinical practice.
Clinical of Infection Diseases - Neuropilin-1 deficiency in vascular smooth muscle cells is associated with hereditary hemorrhagic telangiectasia arteriovenous malformations.
JCI Insights - Clinical impact of the refit CKD-EPI 2021 creatinine-based eGFR equation.
Clinical Chemistry - Accessory genomes drive independent spread of carbapenem-resistant klebsiella pneumoniae clonal groups 258 and 307 in Houston, TX.
MBio - Genetic profiling and biomarkers in peripheral T-cell lymphomas: current role in the diagnostic work-up.
Modern Pathology - CSF kappa free light chains: Cutoff validation for diagnosing multiple sclerosis.
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