Phenotype and Clinical Outcomes of Titin Cardiomyopathy
Improved understanding of dilated cardiomyopathy (DCM) due to titin truncation (TTNtv) may help guide patient stratification. The purpose of this study was to establish relationships among TTNtv genotype, cardiac phenotype, and outcomes in DCM. In this prospective, observational cohort study, DCM pa...
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| Veröffentlicht in: | Journal of the American College of Cardiology 2017-10, Vol.70 (18), p.2264-2274 |
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| creator | Tayal, Upasana Newsome, Simon Buchan, Rachel Whiffin, Nicola Halliday, Brian Lota, Amrit Roberts, Angharad Baksi, A. John Voges, Inga Midwinter, Will Wilk, Alijca Govind, Risha Walsh, Roddy Daubeney, Piers Jarman, Julian W.E. Baruah, Resham Frenneaux, Michael Barton, Paul J. Pennell, Dudley Ware, James S. Prasad, Sanjay K. Cook, Stuart A. |
| description | Improved understanding of dilated cardiomyopathy (DCM) due to titin truncation (TTNtv) may help guide patient stratification.
The purpose of this study was to establish relationships among TTNtv genotype, cardiac phenotype, and outcomes in DCM.
In this prospective, observational cohort study, DCM patients underwent clinical evaluation, late gadolinium enhancement cardiovascular magnetic resonance, TTN sequencing, and adjudicated follow-up blinded to genotype for the primary composite endpoint of cardiovascular death, and major arrhythmic and major heart failure events.
Of 716 subjects recruited (mean age 53.5 ± 14.3 years; 469 men [65.5%]; 577 [80.6%] New York Heart Association function class I/II), 83 (11.6%) had TTNtv. Patients with TTNtv were younger at enrollment (49.0 years vs. 54.1 years; p = 0.002) and had lower indexed left ventricular mass (5.1 g/m2 reduction; padjusted = 0.03) compared with patients without TTNtv. There was no difference in biventricular ejection fraction between TTNtv+/− groups. Overall, 78 of 604 patients (12.9%) met the primary endpoint (median follow-up 3.9 years; interquartile range: 2.0 to 5.8 years), including 9 of 71 patients with TTNtv (12.7%) and 69 of 533 (12.9%) without. There was no difference in the composite primary outcome of cardiovascular death, heart failure, or arrhythmic events, for patients with or without TTNtv (hazard ratio adjusted for primary endpoint: 0.92 [95% confidence interval: 0.45 to 1.87]; p = 0.82).
In this large, prospective, genotype-phenotype study of ambulatory DCM patients, we show that prognostic factors for all-cause DCM also predict outcome in TTNtv DCM, and that TTNtv DCM does not appear to be associated with worse medium-term prognosis.
[Display omitted] |
| doi_str_mv | 10.1016/j.jacc.2017.08.063 |
| format | Article |
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The purpose of this study was to establish relationships among TTNtv genotype, cardiac phenotype, and outcomes in DCM.
In this prospective, observational cohort study, DCM patients underwent clinical evaluation, late gadolinium enhancement cardiovascular magnetic resonance, TTN sequencing, and adjudicated follow-up blinded to genotype for the primary composite endpoint of cardiovascular death, and major arrhythmic and major heart failure events.
Of 716 subjects recruited (mean age 53.5 ± 14.3 years; 469 men [65.5%]; 577 [80.6%] New York Heart Association function class I/II), 83 (11.6%) had TTNtv. Patients with TTNtv were younger at enrollment (49.0 years vs. 54.1 years; p = 0.002) and had lower indexed left ventricular mass (5.1 g/m2 reduction; padjusted = 0.03) compared with patients without TTNtv. There was no difference in biventricular ejection fraction between TTNtv+/− groups. Overall, 78 of 604 patients (12.9%) met the primary endpoint (median follow-up 3.9 years; interquartile range: 2.0 to 5.8 years), including 9 of 71 patients with TTNtv (12.7%) and 69 of 533 (12.9%) without. There was no difference in the composite primary outcome of cardiovascular death, heart failure, or arrhythmic events, for patients with or without TTNtv (hazard ratio adjusted for primary endpoint: 0.92 [95% confidence interval: 0.45 to 1.87]; p = 0.82).
In this large, prospective, genotype-phenotype study of ambulatory DCM patients, we show that prognostic factors for all-cause DCM also predict outcome in TTNtv DCM, and that TTNtv DCM does not appear to be associated with worse medium-term prognosis.
[Display omitted]</description><identifier>ISSN: 0735-1097</identifier><identifier>EISSN: 1558-3597</identifier><identifier>DOI: 10.1016/j.jacc.2017.08.063</identifier><identifier>PMID: 29073955</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alcohol ; Cardiac arrhythmia ; Cardiology ; Cardiomyopathy ; Cardiomyopathy, Dilated - diagnostic imaging ; Cardiomyopathy, Dilated - genetics ; Cardiovascular disease ; Child ; Clinical outcomes ; CMR ; Cohort Studies ; Confidence intervals ; Connectin ; Connectin - genetics ; Coronary vessels ; DCM ; Deoxyribonucleic acid ; Dilated cardiomyopathy ; DNA ; Enrollments ; Female ; Follow-Up Studies ; Gadolinium ; genetics ; Heart ; Heart attacks ; Heart diseases ; Heart failure ; Hospitals ; Humans ; Hypertension ; Magnetic resonance ; Male ; Middle Aged ; Mortality ; Mutation ; Patients ; Phenotype ; Prospective Studies ; Proteins ; Single-Blind Method ; titin ; Treatment Outcome ; Ventricle ; Young Adult</subject><ispartof>Journal of the American College of Cardiology, 2017-10, Vol.70 (18), p.2264-2274</ispartof><rights>2017 The Authors</rights><rights>Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Oct 31, 2017</rights><rights>2017 The Authors 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c549t-8dce6089c612d35ecd84df98728053e95241d2b724d5e4ed105f383d517fa4443</citedby><cites>FETCH-LOGICAL-c549t-8dce6089c612d35ecd84df98728053e95241d2b724d5e4ed105f383d517fa4443</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0735109717394731$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29073955$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tayal, Upasana</creatorcontrib><creatorcontrib>Newsome, Simon</creatorcontrib><creatorcontrib>Buchan, Rachel</creatorcontrib><creatorcontrib>Whiffin, Nicola</creatorcontrib><creatorcontrib>Halliday, Brian</creatorcontrib><creatorcontrib>Lota, Amrit</creatorcontrib><creatorcontrib>Roberts, Angharad</creatorcontrib><creatorcontrib>Baksi, A. John</creatorcontrib><creatorcontrib>Voges, Inga</creatorcontrib><creatorcontrib>Midwinter, Will</creatorcontrib><creatorcontrib>Wilk, Alijca</creatorcontrib><creatorcontrib>Govind, Risha</creatorcontrib><creatorcontrib>Walsh, Roddy</creatorcontrib><creatorcontrib>Daubeney, Piers</creatorcontrib><creatorcontrib>Jarman, Julian W.E.</creatorcontrib><creatorcontrib>Baruah, Resham</creatorcontrib><creatorcontrib>Frenneaux, Michael</creatorcontrib><creatorcontrib>Barton, Paul J.</creatorcontrib><creatorcontrib>Pennell, Dudley</creatorcontrib><creatorcontrib>Ware, James S.</creatorcontrib><creatorcontrib>Prasad, Sanjay K.</creatorcontrib><creatorcontrib>Cook, Stuart A.</creatorcontrib><title>Phenotype and Clinical Outcomes of Titin Cardiomyopathy</title><title>Journal of the American College of Cardiology</title><addtitle>J Am Coll Cardiol</addtitle><description>Improved understanding of dilated cardiomyopathy (DCM) due to titin truncation (TTNtv) may help guide patient stratification.
The purpose of this study was to establish relationships among TTNtv genotype, cardiac phenotype, and outcomes in DCM.
In this prospective, observational cohort study, DCM patients underwent clinical evaluation, late gadolinium enhancement cardiovascular magnetic resonance, TTN sequencing, and adjudicated follow-up blinded to genotype for the primary composite endpoint of cardiovascular death, and major arrhythmic and major heart failure events.
Of 716 subjects recruited (mean age 53.5 ± 14.3 years; 469 men [65.5%]; 577 [80.6%] New York Heart Association function class I/II), 83 (11.6%) had TTNtv. Patients with TTNtv were younger at enrollment (49.0 years vs. 54.1 years; p = 0.002) and had lower indexed left ventricular mass (5.1 g/m2 reduction; padjusted = 0.03) compared with patients without TTNtv. There was no difference in biventricular ejection fraction between TTNtv+/− groups. Overall, 78 of 604 patients (12.9%) met the primary endpoint (median follow-up 3.9 years; interquartile range: 2.0 to 5.8 years), including 9 of 71 patients with TTNtv (12.7%) and 69 of 533 (12.9%) without. There was no difference in the composite primary outcome of cardiovascular death, heart failure, or arrhythmic events, for patients with or without TTNtv (hazard ratio adjusted for primary endpoint: 0.92 [95% confidence interval: 0.45 to 1.87]; p = 0.82).
In this large, prospective, genotype-phenotype study of ambulatory DCM patients, we show that prognostic factors for all-cause DCM also predict outcome in TTNtv DCM, and that TTNtv DCM does not appear to be associated with worse medium-term prognosis.
[Display omitted]</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alcohol</subject><subject>Cardiac arrhythmia</subject><subject>Cardiology</subject><subject>Cardiomyopathy</subject><subject>Cardiomyopathy, Dilated - diagnostic imaging</subject><subject>Cardiomyopathy, Dilated - genetics</subject><subject>Cardiovascular disease</subject><subject>Child</subject><subject>Clinical outcomes</subject><subject>CMR</subject><subject>Cohort Studies</subject><subject>Confidence intervals</subject><subject>Connectin</subject><subject>Connectin - genetics</subject><subject>Coronary vessels</subject><subject>DCM</subject><subject>Deoxyribonucleic acid</subject><subject>Dilated cardiomyopathy</subject><subject>DNA</subject><subject>Enrollments</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gadolinium</subject><subject>genetics</subject><subject>Heart</subject><subject>Heart attacks</subject><subject>Heart diseases</subject><subject>Heart failure</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Magnetic resonance</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Mutation</subject><subject>Patients</subject><subject>Phenotype</subject><subject>Prospective Studies</subject><subject>Proteins</subject><subject>Single-Blind Method</subject><subject>titin</subject><subject>Treatment Outcome</subject><subject>Ventricle</subject><subject>Young Adult</subject><issn>0735-1097</issn><issn>1558-3597</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc2KFDEQx4Mo7rj6Ah6kwYuXbvPZSUCEZfALFtbDeg7ZpNpJ052MSffCvI3P4pOZcdZFPXiqQ_3qR1X9EXpOcEcw6V-P3Wid6ygmssOqwz17gDZECNUyoeVDtMGSiZZgLc_Qk1JGjHGviH6MzqiuLS3EBqnPO4hpOeyhsdE32ynE4OzUXK2LSzOUJg3NdVhC_PF9a7MPaT6kvV12h6fo0WCnAs_u6jn68v7d9fZje3n14dP24rJ1guulVd5Bj5V2PaGeCXBecT9oJanCgoEWlBNPbyTlXgAHT7AYmGJeEDlYzjk7R29P3v16M0O1xSXbyexzmG0-mGSD-bsTw858TbdG9H1PCKuCV3eCnL6tUBYzh-JgmmyEtBZDtJBccqZ1RV_-g45pzbGe94tSlaNHIT1RLqdSMgz3yxBsjsGY0RyDMcdgDFamBlOHXvx5xv3I7yQq8OYEQH3mbYBsigsQHfiQwS3Gp_A__0-KIp8u</recordid><startdate>20171031</startdate><enddate>20171031</enddate><creator>Tayal, Upasana</creator><creator>Newsome, Simon</creator><creator>Buchan, Rachel</creator><creator>Whiffin, Nicola</creator><creator>Halliday, Brian</creator><creator>Lota, Amrit</creator><creator>Roberts, Angharad</creator><creator>Baksi, A. John</creator><creator>Voges, Inga</creator><creator>Midwinter, Will</creator><creator>Wilk, Alijca</creator><creator>Govind, Risha</creator><creator>Walsh, Roddy</creator><creator>Daubeney, Piers</creator><creator>Jarman, Julian W.E.</creator><creator>Baruah, Resham</creator><creator>Frenneaux, Michael</creator><creator>Barton, Paul J.</creator><creator>Pennell, Dudley</creator><creator>Ware, James S.</creator><creator>Prasad, Sanjay K.</creator><creator>Cook, Stuart A.</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><general>Elsevier Biomedical</general><scope>6I.</scope><scope>AAFTH</scope><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>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20171031</creationdate><title>Phenotype and Clinical Outcomes of Titin Cardiomyopathy</title><author>Tayal, Upasana ; Newsome, Simon ; Buchan, Rachel ; Whiffin, Nicola ; Halliday, Brian ; Lota, Amrit ; Roberts, Angharad ; Baksi, A. John ; Voges, Inga ; Midwinter, Will ; Wilk, Alijca ; Govind, Risha ; Walsh, Roddy ; Daubeney, Piers ; Jarman, Julian W.E. ; Baruah, Resham ; Frenneaux, Michael ; Barton, Paul J. ; Pennell, Dudley ; Ware, James S. ; Prasad, Sanjay K. ; Cook, Stuart A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c549t-8dce6089c612d35ecd84df98728053e95241d2b724d5e4ed105f383d517fa4443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alcohol</topic><topic>Cardiac arrhythmia</topic><topic>Cardiology</topic><topic>Cardiomyopathy</topic><topic>Cardiomyopathy, Dilated - diagnostic imaging</topic><topic>Cardiomyopathy, Dilated - genetics</topic><topic>Cardiovascular disease</topic><topic>Child</topic><topic>Clinical outcomes</topic><topic>CMR</topic><topic>Cohort Studies</topic><topic>Confidence intervals</topic><topic>Connectin</topic><topic>Connectin - genetics</topic><topic>Coronary vessels</topic><topic>DCM</topic><topic>Deoxyribonucleic acid</topic><topic>Dilated cardiomyopathy</topic><topic>DNA</topic><topic>Enrollments</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Gadolinium</topic><topic>genetics</topic><topic>Heart</topic><topic>Heart attacks</topic><topic>Heart diseases</topic><topic>Heart failure</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Magnetic resonance</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Mutation</topic><topic>Patients</topic><topic>Phenotype</topic><topic>Prospective Studies</topic><topic>Proteins</topic><topic>Single-Blind Method</topic><topic>titin</topic><topic>Treatment Outcome</topic><topic>Ventricle</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tayal, Upasana</creatorcontrib><creatorcontrib>Newsome, Simon</creatorcontrib><creatorcontrib>Buchan, Rachel</creatorcontrib><creatorcontrib>Whiffin, Nicola</creatorcontrib><creatorcontrib>Halliday, Brian</creatorcontrib><creatorcontrib>Lota, Amrit</creatorcontrib><creatorcontrib>Roberts, Angharad</creatorcontrib><creatorcontrib>Baksi, A. 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John</au><au>Voges, Inga</au><au>Midwinter, Will</au><au>Wilk, Alijca</au><au>Govind, Risha</au><au>Walsh, Roddy</au><au>Daubeney, Piers</au><au>Jarman, Julian W.E.</au><au>Baruah, Resham</au><au>Frenneaux, Michael</au><au>Barton, Paul J.</au><au>Pennell, Dudley</au><au>Ware, James S.</au><au>Prasad, Sanjay K.</au><au>Cook, Stuart A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phenotype and Clinical Outcomes of Titin Cardiomyopathy</atitle><jtitle>Journal of the American College of Cardiology</jtitle><addtitle>J Am Coll Cardiol</addtitle><date>2017-10-31</date><risdate>2017</risdate><volume>70</volume><issue>18</issue><spage>2264</spage><epage>2274</epage><pages>2264-2274</pages><issn>0735-1097</issn><eissn>1558-3597</eissn><abstract>Improved understanding of dilated cardiomyopathy (DCM) due to titin truncation (TTNtv) may help guide patient stratification.
The purpose of this study was to establish relationships among TTNtv genotype, cardiac phenotype, and outcomes in DCM.
In this prospective, observational cohort study, DCM patients underwent clinical evaluation, late gadolinium enhancement cardiovascular magnetic resonance, TTN sequencing, and adjudicated follow-up blinded to genotype for the primary composite endpoint of cardiovascular death, and major arrhythmic and major heart failure events.
Of 716 subjects recruited (mean age 53.5 ± 14.3 years; 469 men [65.5%]; 577 [80.6%] New York Heart Association function class I/II), 83 (11.6%) had TTNtv. Patients with TTNtv were younger at enrollment (49.0 years vs. 54.1 years; p = 0.002) and had lower indexed left ventricular mass (5.1 g/m2 reduction; padjusted = 0.03) compared with patients without TTNtv. There was no difference in biventricular ejection fraction between TTNtv+/− groups. Overall, 78 of 604 patients (12.9%) met the primary endpoint (median follow-up 3.9 years; interquartile range: 2.0 to 5.8 years), including 9 of 71 patients with TTNtv (12.7%) and 69 of 533 (12.9%) without. There was no difference in the composite primary outcome of cardiovascular death, heart failure, or arrhythmic events, for patients with or without TTNtv (hazard ratio adjusted for primary endpoint: 0.92 [95% confidence interval: 0.45 to 1.87]; p = 0.82).
In this large, prospective, genotype-phenotype study of ambulatory DCM patients, we show that prognostic factors for all-cause DCM also predict outcome in TTNtv DCM, and that TTNtv DCM does not appear to be associated with worse medium-term prognosis.
[Display omitted]</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>29073955</pmid><doi>10.1016/j.jacc.2017.08.063</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adolescent Adult Aged Aged, 80 and over Alcohol Cardiac arrhythmia Cardiology Cardiomyopathy Cardiomyopathy, Dilated - diagnostic imaging Cardiomyopathy, Dilated - genetics Cardiovascular disease Child Clinical outcomes CMR Cohort Studies Confidence intervals Connectin Connectin - genetics Coronary vessels DCM Deoxyribonucleic acid Dilated cardiomyopathy DNA Enrollments Female Follow-Up Studies Gadolinium genetics Heart Heart attacks Heart diseases Heart failure Hospitals Humans Hypertension Magnetic resonance Male Middle Aged Mortality Mutation Patients Phenotype Prospective Studies Proteins Single-Blind Method titin Treatment Outcome Ventricle Young Adult |
| title | Phenotype and Clinical Outcomes of Titin Cardiomyopathy |
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