Evidence map›Paper›PMID 34849696›Full record

ArticleEuropean heart journal2022

Calcific aortic valve disease: from molecular and cellular mechanisms to medical therapy.

Simon Kraler, Mark C Blaser, Elena Aikawa, Giovanni G Camici, Thomas F Lüscher

Open access · greenAbstract read
In one paragraph

Article in European heart journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
149citing papers in PubMed, 1 pooled it
27.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

149 citing papers in PubMed, 1 synthesis or guideline pooled it, 278 citations in OpenAlex.

  1. Pooled it
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  9. ILK-Dependent Modulation of DPP4 Prevents Progression of Calcific Aortic Valve Disease.Arteriosclerosis, thrombosis, and vascular biology · 2026
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89 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 3 countries.

Simon KralerCenter for Molecular Cardiology, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.ORCID 0000-0002-8245-7287
Mark C BlaserCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 3 Blackfan Street, Boston, MA 02115, USA.ORCID 0000-0002-3923-9786
Elena AikawaCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 3 Blackfan Street, Boston, MA 02115, USA.
Giovanni G CamiciCenter for Molecular Cardiology, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.ORCID 0000-0002-0523-0695
Thomas F LüscherCenter for Molecular Cardiology, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.ORCID 0000-0002-5259-538X
University of Zurich · CHBrigham and Women's Hospital · US

Funding

Improving Mitral Compensation In Ischemic RegurgitationR01HL141917 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI AIKAWA, ELENA, BISCHOFF, JOYCE E. · 2018 to 2021
$5.6M
Macrophage-derived microcalcificaitonsR01HL136431 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, ELENA · 2017 to 2020
$2.7M
New driver of fibrosis and calcification in CAVDR01HL147095 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, ELENA · 2019 to 2022
$2.4M
NHLBI NIH HHS R01 HL136431NHLBI NIH HHS R01 HL141917NHLBI NIH HHS R01 HL147095
6 · The paper itself

Abstract

Calcific aortic valve disease (CAVD) is a highly prevalent condition that comprises a disease continuum, ranging from microscopic changes to profound fibro-calcific leaflet remodelling, culminating in aortic stenosis, heart failure, and ultimately premature death. Traditional risk factors, such as hypercholesterolaemia and (systolic) hypertension, are shared among atherosclerotic cardiovascular disease and CAVD, yet the molecular and cellular mechanisms differ markedly. Statin-induced low-density lipoprotein cholesterol lowering, a remedy highly effective for secondary prevention of atherosclerotic cardiovascular disease, consistently failed to impact CAVD progression or to improve patient outcomes. However, recently completed phase II trials provide hope that pharmaceutical tactics directed at other targets implicated in CAVD pathogenesis offer an avenue to alter the course of the disease non-invasively. Herein, we delineate key players of CAVD pathobiology, outline mechanisms that entail compromised endothelial barrier function, and promote lipid homing, immune-cell infiltration, and deranged phospho-calcium metabolism that collectively perpetuate a pro-inflammatory/pro-osteogenic milieu in which valvular interstitial cells increasingly adopt myofibro-/osteoblast-like properties, thereby fostering fibro-calcific leaflet remodelling and eventually resulting in left ventricular outflow obstruction. We provide a glimpse into the most promising targets on the horizon, including lipoprotein(a), mineral-binding matrix Gla protein, soluble guanylate cyclase, dipeptidyl peptidase-4 as well as candidates involved in regulating phospho-calcium metabolism and valvular angiotensin II synthesis and ultimately discuss their potential for a future therapy of this insidious disease.

Indexed as

Aortic Valve StenosisCalcinosisAortic ValveCells, CulturedHumansOsteogenesisAgeingCalcific aortic valve diseaseLipoprotein(a)Medical therapyNitric oxideNotch1

Identifiers

PMID34849696
PMCPMC8843796
OpenAlexW3215076242

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.