Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: Structural deterioration and compensatory mechanisms
The progression of compensated hypertrophy to heart failure (HF) is still debated. We investigated patients with isolated valvular aortic stenosis and differing degrees of left ventricular (LV) systolic dysfunction to test the hypothesis that structural remodeling, as well as cell death, contributes...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2003-02, Vol.107 (7), p.984-991 |
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| container_title | Circulation (New York, N.Y.) |
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| creator | HEIN, Stefan ARNON, Eyal KOSTIN, Sawa SCHÖNBURG, Markus ELSÄSSER, Albrecht POLYAKOVA, Victoria BAUER, Erwin P KLÖVEKORN, Wolf-Peter SCHAPER, Jutta |
| description | The progression of compensated hypertrophy to heart failure (HF) is still debated. We investigated patients with isolated valvular aortic stenosis and differing degrees of left ventricular (LV) systolic dysfunction to test the hypothesis that structural remodeling, as well as cell death, contributes to the transition to HF.
Structural alterations were studied in LV myectomies from 3 groups of patients (group 1: ejection fraction [EF] >50%, n=12; group 2: EF 30% to 50%, n=12; group 3: EF |
| doi_str_mv | 10.1161/01.CIR.0000051865.66123.B7 |
| format | Article |
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Structural alterations were studied in LV myectomies from 3 groups of patients (group 1: ejection fraction [EF] >50%, n=12; group 2: EF 30% to 50%, n=12; group 3: EF <30%, n=10) undergoing aortic valve replacement. Control patients were patients with mitral valve stenosis but normal LV (n=6). Myocyte hypertrophy was accompanied by increased nuclear DNA and Sc-35 (splicing factor) content. ACE and TGF-beta1 were upregulated correlating with fibrosis, which increased 2.3-, 2.2-, and 3.2-fold over control in the 3 groups. Myocyte degeneration increased 10, 22, and 32 times over control. A significant correlation exists between EF and myocyte degeneration or fibrosis. Ubiquitin-related autophagic cell death was 0.5 per thousand in control and group 1, 1.05 in group 2, and 6.05 per thousand in group 3. Death by oncosis was 0 per thousand in control, 3 per thousand in group 1, and increased to 5 per thousand (groups 2 and 3). Apoptosis was not detectable in control and group 3, but it was present at 0.02 per thousand in group 1 and 0.01 per thousand in group 2. Cardiomyocyte mitosis was never observed.
These structure-function correlations confirm the hypothesis that transition to HF occurs by fibrosis and myocyte degeneration partially compensated by hypertrophy involving DNA synthesis and transcription. Cell loss, mainly by autophagy and oncosis, contributes significantly to the progression of LV systolic dysfunction.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.CIR.0000051865.66123.B7</identifier><identifier>PMID: 12600911</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Aged ; Aortic Valve Stenosis - complications ; Aortic Valve Stenosis - pathology ; Aortic Valve Stenosis - physiopathology ; Biological and medical sciences ; Capillaries - anatomy & histology ; Capillaries - chemistry ; Cardiology. Vascular system ; Cardiomegaly - complications ; Cardiomegaly - pathology ; Cardiomegaly - physiopathology ; Cell Death ; Cell Nucleus - genetics ; Disease Progression ; DNA - analysis ; Female ; Fibrosis ; Heart ; Heart Failure - etiology ; Heart failure, cardiogenic pulmonary edema, cardiac enlargement ; Hemodynamics ; Humans ; Inflammation - etiology ; Male ; Medical sciences ; Models, Cardiovascular ; Myocytes, Cardiac - pathology ; Myocytes, Cardiac - ultrastructure ; Nuclear Proteins - analysis ; Peptidyl-Dipeptidase A - analysis ; Ribonucleoproteins ; Serine-Arginine Splicing Factors ; Transforming Growth Factor beta - analysis ; Transforming Growth Factor beta1 ; Ventricular Dysfunction, Left - complications ; Ventricular Dysfunction, Left - pathology ; Ventricular Dysfunction, Left - physiopathology ; Ventricular Pressure</subject><ispartof>Circulation (New York, N.Y.), 2003-02, Vol.107 (7), p.984-991</ispartof><rights>2003 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Feb 25 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c413t-83a658b9254537a4f482cf8b31e81e0b68fa69bcb050b155d06c2082257bc2203</citedby><cites>FETCH-LOGICAL-c413t-83a658b9254537a4f482cf8b31e81e0b68fa69bcb050b155d06c2082257bc2203</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3674,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14606732$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12600911$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HEIN, Stefan</creatorcontrib><creatorcontrib>ARNON, Eyal</creatorcontrib><creatorcontrib>KOSTIN, Sawa</creatorcontrib><creatorcontrib>SCHÖNBURG, Markus</creatorcontrib><creatorcontrib>ELSÄSSER, Albrecht</creatorcontrib><creatorcontrib>POLYAKOVA, Victoria</creatorcontrib><creatorcontrib>BAUER, Erwin P</creatorcontrib><creatorcontrib>KLÖVEKORN, Wolf-Peter</creatorcontrib><creatorcontrib>SCHAPER, Jutta</creatorcontrib><title>Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: Structural deterioration and compensatory mechanisms</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>The progression of compensated hypertrophy to heart failure (HF) is still debated. We investigated patients with isolated valvular aortic stenosis and differing degrees of left ventricular (LV) systolic dysfunction to test the hypothesis that structural remodeling, as well as cell death, contributes to the transition to HF.
Structural alterations were studied in LV myectomies from 3 groups of patients (group 1: ejection fraction [EF] >50%, n=12; group 2: EF 30% to 50%, n=12; group 3: EF <30%, n=10) undergoing aortic valve replacement. Control patients were patients with mitral valve stenosis but normal LV (n=6). Myocyte hypertrophy was accompanied by increased nuclear DNA and Sc-35 (splicing factor) content. ACE and TGF-beta1 were upregulated correlating with fibrosis, which increased 2.3-, 2.2-, and 3.2-fold over control in the 3 groups. Myocyte degeneration increased 10, 22, and 32 times over control. A significant correlation exists between EF and myocyte degeneration or fibrosis. Ubiquitin-related autophagic cell death was 0.5 per thousand in control and group 1, 1.05 in group 2, and 6.05 per thousand in group 3. Death by oncosis was 0 per thousand in control, 3 per thousand in group 1, and increased to 5 per thousand (groups 2 and 3). Apoptosis was not detectable in control and group 3, but it was present at 0.02 per thousand in group 1 and 0.01 per thousand in group 2. Cardiomyocyte mitosis was never observed.
These structure-function correlations confirm the hypothesis that transition to HF occurs by fibrosis and myocyte degeneration partially compensated by hypertrophy involving DNA synthesis and transcription. Cell loss, mainly by autophagy and oncosis, contributes significantly to the progression of LV systolic dysfunction.</description><subject>Aged</subject><subject>Aortic Valve Stenosis - complications</subject><subject>Aortic Valve Stenosis - pathology</subject><subject>Aortic Valve Stenosis - physiopathology</subject><subject>Biological and medical sciences</subject><subject>Capillaries - anatomy & histology</subject><subject>Capillaries - chemistry</subject><subject>Cardiology. Vascular system</subject><subject>Cardiomegaly - complications</subject><subject>Cardiomegaly - pathology</subject><subject>Cardiomegaly - physiopathology</subject><subject>Cell Death</subject><subject>Cell Nucleus - genetics</subject><subject>Disease Progression</subject><subject>DNA - analysis</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Heart</subject><subject>Heart Failure - etiology</subject><subject>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</subject><subject>Hemodynamics</subject><subject>Humans</subject><subject>Inflammation - etiology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Models, Cardiovascular</subject><subject>Myocytes, Cardiac - pathology</subject><subject>Myocytes, Cardiac - ultrastructure</subject><subject>Nuclear Proteins - analysis</subject><subject>Peptidyl-Dipeptidase A - analysis</subject><subject>Ribonucleoproteins</subject><subject>Serine-Arginine Splicing Factors</subject><subject>Transforming Growth Factor beta - analysis</subject><subject>Transforming Growth Factor beta1</subject><subject>Ventricular Dysfunction, Left - complications</subject><subject>Ventricular Dysfunction, Left - pathology</subject><subject>Ventricular Dysfunction, Left - physiopathology</subject><subject>Ventricular Pressure</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkduK1TAUhoMoznb0FSQM6F1rDk3aPXfOxsPAgOLhOqTpqu3QJnUlHdhv4SObOhs2mJuwWN-fleQj5IqzknPN3zFeHm6_lWxbijdalVpzIcub-gnZcSWqolJy_5Tscn9f1FKIC_Iixvtcalmr5-SCC51bnO_In68YfiHEOAZPewwzdWFewEeboKPDcQFMGJbhSFOgvR2nFYGOnqYB6LLlcl2EB8Ap2G5LrLP1dACL6Zp-T7i6tKKdaAcJcAxo0zbI-u48J-CRzuAG68c4x5fkWW-nCK9O-yX5-fHDj8Pn4u7Lp9vD-7vCVVymopFWq6bdC5XfWtuqrxrh-qaVHBoOrNVNb_W-dS1TrOVKdUw7wRohVN06IZi8JG8fz10w_F4hJjOP0cE0WQ9hjaaWOSlrkcGr_8D7sKLPdzMi_6NuuOAZun6EHIYYEXqz4DhbPBrOzCbNMG6yNHOWZv5JMzd1Dr8-TVjbGbpz9GQpA29OgI3OTj1a78Z45irNdNYs_wKm1KL7</recordid><startdate>20030225</startdate><enddate>20030225</enddate><creator>HEIN, Stefan</creator><creator>ARNON, Eyal</creator><creator>KOSTIN, Sawa</creator><creator>SCHÖNBURG, Markus</creator><creator>ELSÄSSER, Albrecht</creator><creator>POLYAKOVA, Victoria</creator><creator>BAUER, Erwin P</creator><creator>KLÖVEKORN, Wolf-Peter</creator><creator>SCHAPER, Jutta</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association, Inc</general><scope>IQODW</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>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>20030225</creationdate><title>Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: Structural deterioration and compensatory mechanisms</title><author>HEIN, Stefan ; ARNON, Eyal ; KOSTIN, Sawa ; SCHÖNBURG, Markus ; ELSÄSSER, Albrecht ; POLYAKOVA, Victoria ; BAUER, Erwin P ; KLÖVEKORN, Wolf-Peter ; SCHAPER, Jutta</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c413t-83a658b9254537a4f482cf8b31e81e0b68fa69bcb050b155d06c2082257bc2203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Aged</topic><topic>Aortic Valve Stenosis - complications</topic><topic>Aortic Valve Stenosis - pathology</topic><topic>Aortic Valve Stenosis - physiopathology</topic><topic>Biological and medical sciences</topic><topic>Capillaries - anatomy & histology</topic><topic>Capillaries - chemistry</topic><topic>Cardiology. Vascular system</topic><topic>Cardiomegaly - complications</topic><topic>Cardiomegaly - pathology</topic><topic>Cardiomegaly - physiopathology</topic><topic>Cell Death</topic><topic>Cell Nucleus - genetics</topic><topic>Disease Progression</topic><topic>DNA - analysis</topic><topic>Female</topic><topic>Fibrosis</topic><topic>Heart</topic><topic>Heart Failure - etiology</topic><topic>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</topic><topic>Hemodynamics</topic><topic>Humans</topic><topic>Inflammation - etiology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Models, Cardiovascular</topic><topic>Myocytes, Cardiac - pathology</topic><topic>Myocytes, Cardiac - ultrastructure</topic><topic>Nuclear Proteins - analysis</topic><topic>Peptidyl-Dipeptidase A - analysis</topic><topic>Ribonucleoproteins</topic><topic>Serine-Arginine Splicing Factors</topic><topic>Transforming Growth Factor beta - analysis</topic><topic>Transforming Growth Factor beta1</topic><topic>Ventricular Dysfunction, Left - complications</topic><topic>Ventricular Dysfunction, Left - pathology</topic><topic>Ventricular Dysfunction, Left - physiopathology</topic><topic>Ventricular Pressure</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HEIN, Stefan</creatorcontrib><creatorcontrib>ARNON, Eyal</creatorcontrib><creatorcontrib>KOSTIN, Sawa</creatorcontrib><creatorcontrib>SCHÖNBURG, Markus</creatorcontrib><creatorcontrib>ELSÄSSER, Albrecht</creatorcontrib><creatorcontrib>POLYAKOVA, Victoria</creatorcontrib><creatorcontrib>BAUER, Erwin P</creatorcontrib><creatorcontrib>KLÖVEKORN, Wolf-Peter</creatorcontrib><creatorcontrib>SCHAPER, Jutta</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HEIN, Stefan</au><au>ARNON, Eyal</au><au>KOSTIN, Sawa</au><au>SCHÖNBURG, Markus</au><au>ELSÄSSER, Albrecht</au><au>POLYAKOVA, Victoria</au><au>BAUER, Erwin P</au><au>KLÖVEKORN, Wolf-Peter</au><au>SCHAPER, Jutta</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: Structural deterioration and compensatory mechanisms</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2003-02-25</date><risdate>2003</risdate><volume>107</volume><issue>7</issue><spage>984</spage><epage>991</epage><pages>984-991</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>The progression of compensated hypertrophy to heart failure (HF) is still debated. We investigated patients with isolated valvular aortic stenosis and differing degrees of left ventricular (LV) systolic dysfunction to test the hypothesis that structural remodeling, as well as cell death, contributes to the transition to HF.
Structural alterations were studied in LV myectomies from 3 groups of patients (group 1: ejection fraction [EF] >50%, n=12; group 2: EF 30% to 50%, n=12; group 3: EF <30%, n=10) undergoing aortic valve replacement. Control patients were patients with mitral valve stenosis but normal LV (n=6). Myocyte hypertrophy was accompanied by increased nuclear DNA and Sc-35 (splicing factor) content. ACE and TGF-beta1 were upregulated correlating with fibrosis, which increased 2.3-, 2.2-, and 3.2-fold over control in the 3 groups. Myocyte degeneration increased 10, 22, and 32 times over control. A significant correlation exists between EF and myocyte degeneration or fibrosis. Ubiquitin-related autophagic cell death was 0.5 per thousand in control and group 1, 1.05 in group 2, and 6.05 per thousand in group 3. Death by oncosis was 0 per thousand in control, 3 per thousand in group 1, and increased to 5 per thousand (groups 2 and 3). Apoptosis was not detectable in control and group 3, but it was present at 0.02 per thousand in group 1 and 0.01 per thousand in group 2. Cardiomyocyte mitosis was never observed.
These structure-function correlations confirm the hypothesis that transition to HF occurs by fibrosis and myocyte degeneration partially compensated by hypertrophy involving DNA synthesis and transcription. Cell loss, mainly by autophagy and oncosis, contributes significantly to the progression of LV systolic dysfunction.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>12600911</pmid><doi>10.1161/01.CIR.0000051865.66123.B7</doi><tpages>8</tpages></addata></record> |
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| ispartof | Circulation (New York, N.Y.), 2003-02, Vol.107 (7), p.984-991 |
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| source | MEDLINE; American Heart Association Journals; EZB-FREE-00999 freely available EZB journals; Journals@Ovid Complete |
| subjects | Aged Aortic Valve Stenosis - complications Aortic Valve Stenosis - pathology Aortic Valve Stenosis - physiopathology Biological and medical sciences Capillaries - anatomy & histology Capillaries - chemistry Cardiology. Vascular system Cardiomegaly - complications Cardiomegaly - pathology Cardiomegaly - physiopathology Cell Death Cell Nucleus - genetics Disease Progression DNA - analysis Female Fibrosis Heart Heart Failure - etiology Heart failure, cardiogenic pulmonary edema, cardiac enlargement Hemodynamics Humans Inflammation - etiology Male Medical sciences Models, Cardiovascular Myocytes, Cardiac - pathology Myocytes, Cardiac - ultrastructure Nuclear Proteins - analysis Peptidyl-Dipeptidase A - analysis Ribonucleoproteins Serine-Arginine Splicing Factors Transforming Growth Factor beta - analysis Transforming Growth Factor beta1 Ventricular Dysfunction, Left - complications Ventricular Dysfunction, Left - pathology Ventricular Dysfunction, Left - physiopathology Ventricular Pressure |
| title | Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: Structural deterioration and compensatory mechanisms |
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