Clonal Hematopoiesis Has Prognostic Value in Dilated Cardiomyopathy Independent of Age and Clone Size
Clonal hematopoiesis (CH) gives rise to mutated leukocyte clones that induce cardiovascular inflammation and thereby impact the disease course in atherosclerosis and ischemic heart failure. CH of indeterminate potential refers to a variant allele frequency (VAF) (a marker for clone size) in blood of...
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| Veröffentlicht in: | JACC. Heart failure 2024-05, Vol.12 (5), p.905-914 |
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| creator | Sikking, Maurits A. Stroeks, Sophie L.V.M. Henkens, Michiel T.H.M. Raafs, Anne G. Cossins, Benjamin van Deuren, Rosanne C. Steehouwer, Marlies Riksen, Niels P. van den Wijngaard, Arthur Brunner, Han G. Hoischen, Alexander Verdonschot, Job A.J. Heymans, Stephane R.B. |
| description | Clonal hematopoiesis (CH) gives rise to mutated leukocyte clones that induce cardiovascular inflammation and thereby impact the disease course in atherosclerosis and ischemic heart failure. CH of indeterminate potential refers to a variant allele frequency (VAF) (a marker for clone size) in blood of ≥2%. The impact of CH clones—including small clone sizes (VAF |
| doi_str_mv | 10.1016/j.jchf.2023.06.037 |
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| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2858405968</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S2213177923005097</els_id><sourcerecordid>2858405968</sourcerecordid><originalsourceid>FETCH-LOGICAL-c356t-ee446c7b8fb130893901093872e371734ff32a01d4fbf6cb2e849adb0bc870223</originalsourceid><addsrcrecordid>eNp9kE1LxDAQhoMoKuof8CA5etmaj7ZJwYusHyssKPhxDWk6WbO0TU26wvrrzbKrR-cwM4dnXpgHoXNKMkpoebXMlubDZowwnpEyI1zsoWPGKJ9QIcX-3y6qI3QW45KkkgWVUh6iIy5KLgtGjhFMW9_rFs-g06MfvIPoIp7piJ-DX_Q-js7gd92uALse37pWj9DgqQ6N893aD3r8WOPHvoEBUutH7C2-WQDWfaJSNOAX9w2n6MDqNsLZbp6gt_u71-lsMn96eJzezCeGF-U4Acjz0oha2ppyIiteEUoqLgUDLqjgubWcaUKb3Na2NDUDmVe6qUltpCCM8RN0uc0dgv9cQRxV56KBttU9-FVUTBYyJ0VVyoSyLWqCjzGAVUNwnQ5rRYnaGFZLtTGsNoYVKVUynI4udvmruoPm7-TXZwKutwCkL78cBBWNg95A4wKYUTXe_Zf_A2_Ii_Q</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2858405968</pqid></control><display><type>article</type><title>Clonal Hematopoiesis Has Prognostic Value in Dilated Cardiomyopathy Independent of Age and Clone Size</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Sikking, Maurits A. ; Stroeks, Sophie L.V.M. ; Henkens, Michiel T.H.M. ; Raafs, Anne G. ; Cossins, Benjamin ; van Deuren, Rosanne C. ; Steehouwer, Marlies ; Riksen, Niels P. ; van den Wijngaard, Arthur ; Brunner, Han G. ; Hoischen, Alexander ; Verdonschot, Job A.J. ; Heymans, Stephane R.B.</creator><creatorcontrib>Sikking, Maurits A. ; Stroeks, Sophie L.V.M. ; Henkens, Michiel T.H.M. ; Raafs, Anne G. ; Cossins, Benjamin ; van Deuren, Rosanne C. ; Steehouwer, Marlies ; Riksen, Niels P. ; van den Wijngaard, Arthur ; Brunner, Han G. ; Hoischen, Alexander ; Verdonschot, Job A.J. ; Heymans, Stephane R.B.</creatorcontrib><description>Clonal hematopoiesis (CH) gives rise to mutated leukocyte clones that induce cardiovascular inflammation and thereby impact the disease course in atherosclerosis and ischemic heart failure. CH of indeterminate potential refers to a variant allele frequency (VAF) (a marker for clone size) in blood of ≥2%. The impact of CH clones—including small clone sizes (VAF <0.5%)—in nonischemic dilated cardiomyopathy (DCM) remains largely undetermined.
The authors sought to establish the prognostic impact of CH in DCM including small clones.
CH is determined using an ultrasensitive single-molecule molecular inversion probe technique that allows detection of clones down to a VAF of 0.01%. Cardiac death and all-cause mortality were analyzed using receiver-operating characteristic curve–optimized VAF cutoff values.
A total of 520 DCM patients have been included. A total of 109 patients (21%) had CH driver mutations, of which 45 had a VAF of ≥2% and 31 <0.5%. The median follow-up duration was 6.5 years (IQR: 4.7-9.7 years). DCM patients with CH have a higher risk of cardiac death (HR: 2.33 using a VAF cutoff of 0.36%, 95% CI: 1.24-4.40) and all-cause mortality (HR: 1.72 using a VAF cutoff of 0.06%, 95% CI: 1.10-2.69), independent of age, sex, left ventricular ejection fraction, and NYHA functional classification.
CH predicts cardiac death and all-cause mortality in DCM patients with optimal thresholds for clone size of 0.36% and 0.06%, respectively. Therefore, CH is prognostically relevant, independent of clone size in patients with DCM.
[Display omitted]</description><identifier>ISSN: 2213-1779</identifier><identifier>EISSN: 2213-1787</identifier><identifier>DOI: 10.1016/j.jchf.2023.06.037</identifier><identifier>PMID: 37638520</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Age Factors ; Aged ; Cardiomyopathy, Dilated - genetics ; Cardiomyopathy, Dilated - physiopathology ; clonal hematopoiesis ; Clonal Hematopoiesis - genetics ; dilated cardiomyopathy ; Female ; Gene Frequency ; heart failure ; Humans ; Male ; Middle Aged ; Mutation ; Prognosis</subject><ispartof>JACC. Heart failure, 2024-05, Vol.12 (5), p.905-914</ispartof><rights>2024 American College of Cardiology Foundation</rights><rights>Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-ee446c7b8fb130893901093872e371734ff32a01d4fbf6cb2e849adb0bc870223</citedby><cites>FETCH-LOGICAL-c356t-ee446c7b8fb130893901093872e371734ff32a01d4fbf6cb2e849adb0bc870223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37638520$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sikking, Maurits A.</creatorcontrib><creatorcontrib>Stroeks, Sophie L.V.M.</creatorcontrib><creatorcontrib>Henkens, Michiel T.H.M.</creatorcontrib><creatorcontrib>Raafs, Anne G.</creatorcontrib><creatorcontrib>Cossins, Benjamin</creatorcontrib><creatorcontrib>van Deuren, Rosanne C.</creatorcontrib><creatorcontrib>Steehouwer, Marlies</creatorcontrib><creatorcontrib>Riksen, Niels P.</creatorcontrib><creatorcontrib>van den Wijngaard, Arthur</creatorcontrib><creatorcontrib>Brunner, Han G.</creatorcontrib><creatorcontrib>Hoischen, Alexander</creatorcontrib><creatorcontrib>Verdonschot, Job A.J.</creatorcontrib><creatorcontrib>Heymans, Stephane R.B.</creatorcontrib><title>Clonal Hematopoiesis Has Prognostic Value in Dilated Cardiomyopathy Independent of Age and Clone Size</title><title>JACC. Heart failure</title><addtitle>JACC Heart Fail</addtitle><description>Clonal hematopoiesis (CH) gives rise to mutated leukocyte clones that induce cardiovascular inflammation and thereby impact the disease course in atherosclerosis and ischemic heart failure. CH of indeterminate potential refers to a variant allele frequency (VAF) (a marker for clone size) in blood of ≥2%. The impact of CH clones—including small clone sizes (VAF <0.5%)—in nonischemic dilated cardiomyopathy (DCM) remains largely undetermined.
The authors sought to establish the prognostic impact of CH in DCM including small clones.
CH is determined using an ultrasensitive single-molecule molecular inversion probe technique that allows detection of clones down to a VAF of 0.01%. Cardiac death and all-cause mortality were analyzed using receiver-operating characteristic curve–optimized VAF cutoff values.
A total of 520 DCM patients have been included. A total of 109 patients (21%) had CH driver mutations, of which 45 had a VAF of ≥2% and 31 <0.5%. The median follow-up duration was 6.5 years (IQR: 4.7-9.7 years). DCM patients with CH have a higher risk of cardiac death (HR: 2.33 using a VAF cutoff of 0.36%, 95% CI: 1.24-4.40) and all-cause mortality (HR: 1.72 using a VAF cutoff of 0.06%, 95% CI: 1.10-2.69), independent of age, sex, left ventricular ejection fraction, and NYHA functional classification.
CH predicts cardiac death and all-cause mortality in DCM patients with optimal thresholds for clone size of 0.36% and 0.06%, respectively. Therefore, CH is prognostically relevant, independent of clone size in patients with DCM.
[Display omitted]</description><subject>Adult</subject><subject>Age Factors</subject><subject>Aged</subject><subject>Cardiomyopathy, Dilated - genetics</subject><subject>Cardiomyopathy, Dilated - physiopathology</subject><subject>clonal hematopoiesis</subject><subject>Clonal Hematopoiesis - genetics</subject><subject>dilated cardiomyopathy</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>heart failure</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Prognosis</subject><issn>2213-1779</issn><issn>2213-1787</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LxDAQhoMoKuof8CA5etmaj7ZJwYusHyssKPhxDWk6WbO0TU26wvrrzbKrR-cwM4dnXpgHoXNKMkpoebXMlubDZowwnpEyI1zsoWPGKJ9QIcX-3y6qI3QW45KkkgWVUh6iIy5KLgtGjhFMW9_rFs-g06MfvIPoIp7piJ-DX_Q-js7gd92uALse37pWj9DgqQ6N893aD3r8WOPHvoEBUutH7C2-WQDWfaJSNOAX9w2n6MDqNsLZbp6gt_u71-lsMn96eJzezCeGF-U4Acjz0oha2ppyIiteEUoqLgUDLqjgubWcaUKb3Na2NDUDmVe6qUltpCCM8RN0uc0dgv9cQRxV56KBttU9-FVUTBYyJ0VVyoSyLWqCjzGAVUNwnQ5rRYnaGFZLtTGsNoYVKVUynI4udvmruoPm7-TXZwKutwCkL78cBBWNg95A4wKYUTXe_Zf_A2_Ii_Q</recordid><startdate>202405</startdate><enddate>202405</enddate><creator>Sikking, Maurits A.</creator><creator>Stroeks, Sophie L.V.M.</creator><creator>Henkens, Michiel T.H.M.</creator><creator>Raafs, Anne G.</creator><creator>Cossins, Benjamin</creator><creator>van Deuren, Rosanne C.</creator><creator>Steehouwer, Marlies</creator><creator>Riksen, Niels P.</creator><creator>van den Wijngaard, Arthur</creator><creator>Brunner, Han G.</creator><creator>Hoischen, Alexander</creator><creator>Verdonschot, Job A.J.</creator><creator>Heymans, Stephane R.B.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202405</creationdate><title>Clonal Hematopoiesis Has Prognostic Value in Dilated Cardiomyopathy Independent of Age and Clone Size</title><author>Sikking, Maurits A. ; Stroeks, Sophie L.V.M. ; Henkens, Michiel T.H.M. ; Raafs, Anne G. ; Cossins, Benjamin ; van Deuren, Rosanne C. ; Steehouwer, Marlies ; Riksen, Niels P. ; van den Wijngaard, Arthur ; Brunner, Han G. ; Hoischen, Alexander ; Verdonschot, Job A.J. ; Heymans, Stephane R.B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-ee446c7b8fb130893901093872e371734ff32a01d4fbf6cb2e849adb0bc870223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Age Factors</topic><topic>Aged</topic><topic>Cardiomyopathy, Dilated - genetics</topic><topic>Cardiomyopathy, Dilated - physiopathology</topic><topic>clonal hematopoiesis</topic><topic>Clonal Hematopoiesis - genetics</topic><topic>dilated cardiomyopathy</topic><topic>Female</topic><topic>Gene Frequency</topic><topic>heart failure</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Prognosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sikking, Maurits A.</creatorcontrib><creatorcontrib>Stroeks, Sophie L.V.M.</creatorcontrib><creatorcontrib>Henkens, Michiel T.H.M.</creatorcontrib><creatorcontrib>Raafs, Anne G.</creatorcontrib><creatorcontrib>Cossins, Benjamin</creatorcontrib><creatorcontrib>van Deuren, Rosanne C.</creatorcontrib><creatorcontrib>Steehouwer, Marlies</creatorcontrib><creatorcontrib>Riksen, Niels P.</creatorcontrib><creatorcontrib>van den Wijngaard, Arthur</creatorcontrib><creatorcontrib>Brunner, Han G.</creatorcontrib><creatorcontrib>Hoischen, Alexander</creatorcontrib><creatorcontrib>Verdonschot, Job A.J.</creatorcontrib><creatorcontrib>Heymans, Stephane R.B.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>JACC. Heart failure</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sikking, Maurits A.</au><au>Stroeks, Sophie L.V.M.</au><au>Henkens, Michiel T.H.M.</au><au>Raafs, Anne G.</au><au>Cossins, Benjamin</au><au>van Deuren, Rosanne C.</au><au>Steehouwer, Marlies</au><au>Riksen, Niels P.</au><au>van den Wijngaard, Arthur</au><au>Brunner, Han G.</au><au>Hoischen, Alexander</au><au>Verdonschot, Job A.J.</au><au>Heymans, Stephane R.B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clonal Hematopoiesis Has Prognostic Value in Dilated Cardiomyopathy Independent of Age and Clone Size</atitle><jtitle>JACC. Heart failure</jtitle><addtitle>JACC Heart Fail</addtitle><date>2024-05</date><risdate>2024</risdate><volume>12</volume><issue>5</issue><spage>905</spage><epage>914</epage><pages>905-914</pages><issn>2213-1779</issn><eissn>2213-1787</eissn><abstract>Clonal hematopoiesis (CH) gives rise to mutated leukocyte clones that induce cardiovascular inflammation and thereby impact the disease course in atherosclerosis and ischemic heart failure. CH of indeterminate potential refers to a variant allele frequency (VAF) (a marker for clone size) in blood of ≥2%. The impact of CH clones—including small clone sizes (VAF <0.5%)—in nonischemic dilated cardiomyopathy (DCM) remains largely undetermined.
The authors sought to establish the prognostic impact of CH in DCM including small clones.
CH is determined using an ultrasensitive single-molecule molecular inversion probe technique that allows detection of clones down to a VAF of 0.01%. Cardiac death and all-cause mortality were analyzed using receiver-operating characteristic curve–optimized VAF cutoff values.
A total of 520 DCM patients have been included. A total of 109 patients (21%) had CH driver mutations, of which 45 had a VAF of ≥2% and 31 <0.5%. The median follow-up duration was 6.5 years (IQR: 4.7-9.7 years). DCM patients with CH have a higher risk of cardiac death (HR: 2.33 using a VAF cutoff of 0.36%, 95% CI: 1.24-4.40) and all-cause mortality (HR: 1.72 using a VAF cutoff of 0.06%, 95% CI: 1.10-2.69), independent of age, sex, left ventricular ejection fraction, and NYHA functional classification.
CH predicts cardiac death and all-cause mortality in DCM patients with optimal thresholds for clone size of 0.36% and 0.06%, respectively. Therefore, CH is prognostically relevant, independent of clone size in patients with DCM.
[Display omitted]</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>37638520</pmid><doi>10.1016/j.jchf.2023.06.037</doi><tpages>10</tpages></addata></record> |
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| subjects | Adult Age Factors Aged Cardiomyopathy, Dilated - genetics Cardiomyopathy, Dilated - physiopathology clonal hematopoiesis Clonal Hematopoiesis - genetics dilated cardiomyopathy Female Gene Frequency heart failure Humans Male Middle Aged Mutation Prognosis |
| title | Clonal Hematopoiesis Has Prognostic Value in Dilated Cardiomyopathy Independent of Age and Clone Size |
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