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ArticleClinical research in cardiology : official journal of the German Cardiac Society2025

Mutational landscape and impact of clonal hematopoiesis of indeterminate potential in severe aortic valve stenosis.

Raúl Nicolas Jamin, Baravan Al-Kassou, Theresa Kleuker, Jasmin Shamekhi, Benedikt Bartsch, Ansgar Ackerschott, Muntadher Al Zaidi, Hannah Billig, Claus Moritz Graef, Malte Kelm and 4 more

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Article in Clinical research in cardiology : official journal of the German Cardiac Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
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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

14 authors.

Raúl Nicolas Jamin *Heart Center Bonn, Clinic for Internal Medicine II, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany. Raul_nicolas.jamin@ukbonn.de.ORCID http://orcid.org/0009-0003-2084-8463
Baravan Al-Kassou *Heart Center Bonn, Clinic for Internal Medicine II, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.
Theresa KleukerHeart Center Bonn, Clinic for Internal Medicine II, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.
Jasmin ShamekhiHeart Center Bonn, Clinic for Internal Medicine II, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.
Benedikt BartschHeart Center Bonn, Clinic for Internal Medicine II, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.
Ansgar AckerschottHeart Center Bonn, Clinic for Internal Medicine II, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.
Muntadher Al ZaidiHeart Center Bonn, Clinic for Internal Medicine II, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.
Hannah BilligHeart Center Bonn, Clinic for Internal Medicine II, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.
Claus Moritz GraefDepartment I of Internal Medicine, University Hospital, 50937, Cologne, Germany.
Malte KelmDepartment of Cardiology, Pulmonology and Vascular Medicine, University Hospital, Heinrich Heine University, 40225, Düsseldorf, Germany.
Stephan BaldusHeart Center, Department of Cardiology, University Hospital Cologne, 50937, Cologne, Germany.
Georg NickenigHeart Center Bonn, Clinic for Internal Medicine II, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.
Eicke LatzGerman Rheumatism Research Centre, 10117, Berlin, Germany.
Sebastian ZimmerHeart Center Bonn, Clinic for Internal Medicine II, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Funding

Deutsche Forschungsgemeinschaft 397484323
6 · The paper itself

Abstract

backgroundClonal hematopoiesis of indeterminate potential (CHIP) has been progressively established as a risk factor for cardiovascular disease and associated with worsened outcomes in patients with aortic valve stenosis (AVS). This cohort study aimed to evaluate the mutational landscape of CHIP and its' influence on clinical outcomes.

methods194 patients with AVS undergoing transcatheter aortic valve replacement (TAVR) were sequenced using a capture panel for multiple CH driver mutations and follow up conducted for three years.

resultsWe found high prevalences (77.8%) of a broad spectrum of CH-driver mutations across 38 genes, with 34% of patients fulfilling the diagnostic criteria for CHIP. Evaluating the impact of CHIP driver mutations on outcomes, the presence of CHIP was associated with mortality only when adjusting for confounding factors (HR: 2.143, 95% CI: 1.029-4.461, p = 0.042), while the presence of CH driver mutations at low VAF showed no association with mortality (p = 0.377). However, when excluding DNMT3A-CHIP, we found a significant association of CHIP with mortality in univariate (p = 0.022) and multivariable (HR: 2.976, 95% CI: 1.381-6.411, p = 0.005) analyses.

conclusionsAs the first study to evaluate a broad spectrum of CH driver mutations at all variant allele frequencies in the context of aortic valve stenosis, we found CHIP to be a frequent phenomenon and CH-driver mutations to be highly prevalent in patients with severe AVS. CHIP, other than DNMT3A-CHIP, was associated with increased mortality even after successful TAVR. The presence of CH driver mutations at low allele frequencies was not associated with mortality.

Indexed as

Aortic valve stenosisClonal hematopoiesisTranscatheter aortic valve replacement

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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.