<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v2.0 20040830//EN" "journalpublishing.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="2.0" xml:lang="en" article-type="letter"><front><journal-meta><journal-id journal-id-type="nlm-ta">JMIR Aging</journal-id><journal-id journal-id-type="publisher-id">aging</journal-id><journal-id journal-id-type="index">31</journal-id><journal-title>JMIR Aging</journal-title><abbrev-journal-title>JMIR Aging</abbrev-journal-title><issn pub-type="epub">2561-7605</issn></journal-meta><article-meta><article-id pub-id-type="publisher-id">56345</article-id><article-id pub-id-type="doi">10.2196/56345</article-id><title-group><article-title>The Frailty Trajectory&#x2019;s Additional Edge Over the Frailty Index: Retrospective Cohort Study of Veterans With Heart Failure</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name name-style="western"><surname>Razjouyan</surname><given-names>Javad</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Orkaby</surname><given-names>Ariela R</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Horstman</surname><given-names>Molly J</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Goyal</surname><given-names>Parag</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Intrator</surname><given-names>Orna</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff7">7</xref><xref ref-type="aff" rid="aff8">8</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Naik</surname><given-names>Aanand D</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff9">9</xref><xref ref-type="aff" rid="aff10">10</xref></contrib></contrib-group><aff id="aff1"><institution>Baylor College of Medicine</institution>, <addr-line>Houston</addr-line><addr-line>TX</addr-line>, <country>United States</country></aff><aff id="aff2"><institution>VA Health Services Research &#x0026; Development, Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey VA Medical Center</institution>, <addr-line>Houston</addr-line><addr-line>TX</addr-line>, <country>United States</country></aff><aff id="aff3"><institution>Big Data Scientist Training Enhancement Program, VA Office of Research and Development</institution>, <addr-line>Washington</addr-line><addr-line>DC</addr-line>, <country>United States</country></aff><aff id="aff4"><institution>New England Geriatrics Research, Education, and Clinical Center, VA Boston Health Care System</institution>, <addr-line>Boston</addr-line><addr-line>MA</addr-line>, <country>United States</country></aff><aff id="aff5"><institution>Brigham &#x0026; Women's Hospital, Harvard Medical School</institution>, <addr-line>Boston</addr-line><addr-line>MA</addr-line>, <country>United States</country></aff><aff id="aff6"><institution>Division of General Internal Medicine, Department of Medicine, Weill Medical College of Cornell University</institution>, <addr-line>New York</addr-line><addr-line>NY</addr-line>, <country>United States</country></aff><aff id="aff7"><institution>Geriatrics and Extended Care Data Analysis Center, Canandaigua VA Medical Center</institution>, <addr-line>Canandaigua</addr-line><addr-line>NY</addr-line>, <country>United States</country></aff><aff id="aff8"><institution>Public Health Sciences, University of Rochester School of Medicine and Dentistry</institution>, <addr-line>Rochester</addr-line><addr-line>NY</addr-line>, <country>United States</country></aff><aff id="aff9"><institution>Department of Management, Policy, and Community Health, School of Public Health, University of Texas Health Science Center</institution>, <addr-line>Houston</addr-line><addr-line>TX</addr-line>, <country>United States</country></aff><aff id="aff10"><institution>Institute on Aging, University of Texas Health Science Center</institution>, <addr-line>Houston</addr-line><addr-line>TX</addr-line>, <country>United States</country></aff><contrib-group><contrib contrib-type="editor"><name name-style="western"><surname>Fan</surname><given-names>Qiping</given-names></name></contrib></contrib-group><contrib-group><contrib contrib-type="reviewer"><name name-style="western"><surname>Hassan</surname><given-names>Ahmed</given-names></name></contrib><contrib contrib-type="reviewer"><name name-style="western"><surname>Li</surname><given-names>Xiangwei</given-names></name></contrib></contrib-group><author-notes><corresp>Correspondence to Javad Razjouyan, PhD<email>javad.razjouyan@bcm.edu</email></corresp></author-notes><pub-date pub-type="collection"><year>2024</year></pub-date><pub-date pub-type="epub"><day>27</day><month>6</month><year>2024</year></pub-date><volume>7</volume><elocation-id>e56345</elocation-id><history><date date-type="received"><day>13</day><month>01</month><year>2024</year></date><date date-type="rev-recd"><day>29</day><month>04</month><year>2024</year></date><date date-type="accepted"><day>29</day><month>04</month><year>2024</year></date></history><copyright-statement>&#x00A9; Javad Razjouyan, Ariela Orkaby, Molly Horstman, Parag Goyal, Orna Intrator, Aanand D Naik. Originally published in JMIR Aging (<ext-link ext-link-type="uri" xlink:href="https://aging.jmir.org">https://aging.jmir.org</ext-link>), 27.6.2024. </copyright-statement><copyright-year>2024</copyright-year><license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">https://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Aging, is properly cited. The complete bibliographic information, a link to the original publication on <ext-link ext-link-type="uri" xlink:href="https://aging.jmir.org">https://aging.jmir.org</ext-link>, as well as this copyright and license information must be included.</p></license><self-uri xlink:type="simple" xlink:href="https://aging.jmir.org/2024/1/e56345"/><kwd-group><kwd>gerontology</kwd><kwd>geriatric</kwd><kwd>geriatrics</kwd><kwd>older adult</kwd><kwd>older adults</kwd><kwd>elder</kwd><kwd>elderly</kwd><kwd>older person</kwd><kwd>older people</kwd><kwd>ageing</kwd><kwd>aging</kwd><kwd>frailty</kwd><kwd>frailty index</kwd><kwd>frailty trajectory</kwd><kwd>frail</kwd><kwd>weak</kwd><kwd>weakness</kwd><kwd>heart failure</kwd><kwd>HF</kwd><kwd>cardiovascular disease</kwd><kwd>CVD</kwd><kwd>congestive heart failure</kwd><kwd>CHF</kwd><kwd>myocardial infarction</kwd><kwd>MI</kwd><kwd>unstable angina</kwd><kwd>angina</kwd><kwd>cardiac arrest</kwd><kwd>atherosclerosis</kwd><kwd>cardiology</kwd><kwd>cardiac</kwd><kwd>cardiologist</kwd><kwd>cardiologists</kwd></kwd-group></article-meta></front><body><sec id="s1" sec-type="intro"><title>Introduction</title><p>Individuals with heart failure (HF) have a high burden of health care utilization, costs, and morbidity in the year following hospitalization for an acute HF exacerbation. Frailty, which has been described as increased vulnerability to adverse events, is common among those with HF and increases with age [<xref ref-type="bibr" rid="ref1">1</xref>]. Health systems worldwide are integrating automated tools within electronic health records to measure frailty. However, using longitudinal data to measure frailty and better predict outcomes among those with HF has rarely been considered [<xref ref-type="bibr" rid="ref2">2</xref>-<xref ref-type="bibr" rid="ref5">5</xref>]. We sought to evaluate the predictive value of adding longitudinal data to a standard frailty index (FI) and evaluate predictions of 1-year outcomes in patients with HF.</p></sec><sec id="s2" sec-type="methods"><title>Methods</title><sec id="s2-1"><title>Study Design</title><p>This was a retrospective cohort study that used national Veterans Health Administration (VA) data. Veterans aged &#x2265;50 years with an index hospital admission for HF from 2016 to 2019 were included. We excluded veterans with &#x003C;2 primary care visits in the 3 years before their date of admission to indicate regular use of VA care. We included those with documentation of ejection fraction. We used the validated VA FI, which captures 31 deficits in health based on <italic>International Classification of Diseases, Tenth Revision</italic>, and Current Procedural Terminology codes [<xref ref-type="bibr" rid="ref6">6</xref>]. We estimated the FI for each preceding year, without overlap. We fit a linear line to 3 calculated FIs for each year prior to the index date of admission and reported the slope and intercept individually. This method provided a 3-year longitudinal estimate of frailty at admission. We used 1-year all-cause mortality following the index date of admission as the primary outcome. We reported the area under the curve (AUC) for predicting outcomes, using logistic regression. We estimated two AUCs: (1) FI at the time of admission (AUC<sub>FI</sub>) and (2) FI at time of admission plus slope and intercept (AUC<sub>frailty trajectory (FT)+FI</sub>). Changes in the AUCs were reported as the percentage of improvement (&#x0394;<sub>AUC</sub> = 100% &#x00D7; [AUC<sub>FT+FI</sub> &#x2013; AUC<sub>FI</sub>]/AUC<sub>FI</sub>). We recursively calculated the AUCs and &#x0394;<sub>AUC</sub> by including patients whose FIs at admission were &#x003C;0.1 and, at each step, increased the FI level by 0.01 to 0.4.</p></sec><sec id="s2-2"><title>Ethical Considerations</title><p>The study protocol was approved by the Research &#x0026; Development Committee of the Michael E. DeBakey VA Medical Center and Baylor College of Medicine Institutional Review Board (institutional review board number: H-464220).</p></sec></sec><sec id="s3" sec-type="results"><title>Results</title><p>In total, 54,774 veterans were included (age: mean 73.3, SD 10.1 y; BMI: mean 30.1, SD 7.5 kg/m<sup>2</sup>; male: n=53,899, 98.4%; White: n=30,406, 55.5%; <xref ref-type="table" rid="table1">Table 1</xref>). <xref ref-type="fig" rid="figure1">Figure 1</xref> shows the AUC<sub>FI</sub> and AUC<sub>FT+FI</sub> across the distribution of frailty ranges, from prefrail (FI: 0.1-0.2) to frail; an FI of 0.2 is equivalent to an accumulation of 7 deficits among 31 variables, and the &#x0394;<sub>AUC</sub> is also displayed. For all veterans across all FI thresholds, the AUC improved by at least 4.1% when adding the FT to the FI. The highest &#x0394;<sub>AUC</sub> (24%) was observed for FIs of 0.13 to 0.16, and it decreased to &#x2264;10% for FIs of &#x2265;0.2.</p><table-wrap id="t1" position="float"><label>Table 1.</label><caption><p>Characteristics of patients (N=54,774) with an index admission to the Veterans Health Administration for heart failure from January 1, 2016, to January 1, 2020.</p></caption><table id="table1" frame="hsides" rules="groups"><thead><tr><td align="left" valign="bottom" colspan="2">Characteristics</td><td align="left" valign="bottom">Patients</td></tr></thead><tbody><tr><td align="left" valign="top" colspan="2">Admit year 2016, n (%)</td><td align="left" valign="top">12,875 (23.5)</td></tr><tr><td align="left" valign="top" colspan="2">Admit year 2017, n (%)</td><td align="left" valign="top">13,585 (24.8)</td></tr><tr><td align="left" valign="top" colspan="2">Admit year 2018, n (%)</td><td align="left" valign="top">14,082 (25.7)</td></tr><tr><td align="left" valign="top" colspan="2">Admit year 2019, n (%)</td><td align="left" valign="top">14,232 (26)</td></tr><tr><td align="left" valign="top" colspan="2"><bold>Age (y), mean (SD)</bold></td><td align="left" valign="top">73.3 (10.1)</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">&#x003C;65, n (%)</td><td align="left" valign="top">9776 (17.8)</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">65&#x2010;75, n (%)</td><td align="left" valign="top">22,772 (41.6)</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">&#x2265;85, n (%)</td><td align="left" valign="top">22,226 (40.6)</td></tr><tr><td align="left" valign="top" colspan="3"><bold>Sex, n (%)</bold></td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">Male</td><td align="left" valign="top">53,899 (98.4)</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">Female</td><td align="char" char="." valign="top">875 (1.6)</td></tr><tr><td align="left" valign="top" colspan="3"><bold>Race, n (%)</bold></td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">White</td><td align="left" valign="top">30,406 (55.5)</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">Black</td><td align="left" valign="top">9340 (17.1)</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">Other<sup><xref ref-type="table-fn" rid="table1fn1">a</xref></sup></td><td align="left" valign="top">15,028 (27.4)</td></tr><tr><td align="left" valign="top" colspan="2">Hispanic ethnicity, n (%)</td><td align="left" valign="top">2093 (3.8)</td></tr><tr><td align="left" valign="top" colspan="2"><bold>BMI (kg/m</bold><sup><bold>2</bold></sup><bold>), mean (SD)</bold></td><td align="left" valign="top">30.1 (7.5)</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">&#x2265;30, n (%)</td><td align="left" valign="top">24,352 (44.5)</td></tr><tr><td align="left" valign="top" colspan="2"><bold>Frailty status (frailty index), mean (SD)</bold></td><td align="left" valign="top">0.35 (0.11)</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">Robust (&#x003C;0.1), n (%)<sup><xref ref-type="table-fn" rid="table1fn2">b</xref></sup></td><td align="left" valign="top">297 (0.5)</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">Prefrail (0.1&#x2010;0.2), n (%)<sup><xref ref-type="table-fn" rid="table1fn2">b</xref></sup></td><td align="left" valign="top">5715 (10.5)</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">Frail (&#x003E;0.2), n (%)<sup><xref ref-type="table-fn" rid="table1fn2">b</xref></sup></td><td align="left" valign="top">48,762 (89)</td></tr><tr><td align="left" valign="top" colspan="3"><bold>All-cause mortality, n (%)</bold></td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">30-day mortality</td><td align="left" valign="top">2848 (5.2)</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">1-year mortality</td><td align="left" valign="top">14,460 (26.4)</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">All-time mortality</td><td align="left" valign="top">37,027 (67.6)</td></tr><tr><td align="left" valign="top" colspan="2">Time to death (mo), median (IQR)</td><td align="left" valign="top">18.2 (5.6-36.4)</td></tr><tr><td align="left" valign="top" colspan="2">HFrEF<sup><xref ref-type="table-fn" rid="table1fn3">c</xref></sup>, n (%)</td><td align="left" valign="top">27,223 (49.7)</td></tr><tr><td align="left" valign="top" colspan="2">HFmEF<sup><xref ref-type="table-fn" rid="table1fn4">d</xref></sup>, n (%)</td><td align="left" valign="top">4546 (8.3)</td></tr><tr><td align="left" valign="top" colspan="2">HFpEF<sup><xref ref-type="table-fn" rid="table1fn5">e</xref></sup>, n (%)</td><td align="left" valign="top">23,005 (42.0)</td></tr><tr><td align="left" valign="top" colspan="2">Living in a CLC<sup><xref ref-type="table-fn" rid="table1fn6">f</xref></sup>, n (%)</td><td align="left" valign="top">1808 (3.3)</td></tr></tbody></table><table-wrap-foot><fn id="table1fn1"><p><sup>a</sup>&#x201C;Other&#x201D; includes Asian, American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, and unknown.</p></fn><fn id="table1fn2"><p><sup>b</sup>Standardized frailty status cut points drawn from validated studies [<xref ref-type="bibr" rid="ref6">6</xref>].</p></fn><fn id="table1fn3"><p><sup>c</sup>HFrEF: heart failure with reduced ejection fraction of &#x003C;40%.</p></fn><fn id="table1fn4"><p><sup>d</sup>HFmEF: heart failure with modified reduced ejection fraction of 40%-50%.</p></fn><fn id="table1fn5"><p><sup>e</sup>HFpEF: heart failure with preserved ejection fraction of &#x003E;50%.</p></fn><fn id="table1fn6"><p><sup>f</sup>CLC: community living center.</p></fn></table-wrap-foot></table-wrap><fig position="float" id="figure1"><label>Figure 1.</label><caption><p>AUCs for patients who were admitted, for the first time, to the Veterans Health Administration for heart failure from January 1, 2016, to January 1, 2020, and had an FI of 0.1-0.4 (as shown on the x-axis in increments of 0.01). We compared the AUCs of FIs (in blue; AUC<sub>FI</sub>) versus the AUCs of FIs and FTs combined (in orange; AUC<sub>FI+FT</sub>). The percentage of improvement in AUCs resulting from the addition of the FT to the FI was reported in black (&#x0394;<sub>AUC</sub>) and calculated by using the following formula: <inline-formula><mml:math id="ieqn1"><mml:mstyle displaystyle="true" scriptlevel="0"><mml:mrow><mml:msub><mml:mi mathvariant="normal">&#x0394;</mml:mi><mml:mrow><mml:mi>A</mml:mi><mml:mi>U</mml:mi><mml:mi>C</mml:mi></mml:mrow></mml:msub><mml:mo>=</mml:mo><mml:mtext>&#x00A0;</mml:mtext><mml:mfrac><mml:mrow><mml:mo>(</mml:mo><mml:mrow><mml:mi>A</mml:mi><mml:mi>U</mml:mi><mml:msub><mml:mi>C</mml:mi><mml:mrow><mml:mi>F</mml:mi><mml:mi>I</mml:mi><mml:mo>+</mml:mo><mml:mi>F</mml:mi><mml:mi>T</mml:mi></mml:mrow></mml:msub><mml:mo>&#x2212;</mml:mo><mml:mi>A</mml:mi><mml:mi>U</mml:mi><mml:msub><mml:mi>C</mml:mi><mml:mrow><mml:mi>F</mml:mi><mml:mi>I</mml:mi></mml:mrow></mml:msub></mml:mrow><mml:mo>)</mml:mo></mml:mrow><mml:mrow><mml:mi>A</mml:mi><mml:mi>U</mml:mi><mml:msub><mml:mi>C</mml:mi><mml:mrow><mml:mi>F</mml:mi><mml:mi>I</mml:mi></mml:mrow></mml:msub></mml:mrow></mml:mfrac><mml:mtext>&#x00A0;</mml:mtext><mml:mo>&#x00D7;</mml:mo><mml:mn>100</mml:mn></mml:mrow></mml:mstyle></mml:math></inline-formula>. AUC: area under the curve; FI: frailty index; FT: frailty trajectory.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="aging_v7i1e56345_fig01.png"/></fig></sec><sec id="s4" sec-type="discussion"><title>Discussion</title><p>In a national cohort of veterans who were admitted to the VA for HF, the addition of longitudinal FT data resulted in a clinically significant (up to 24%) improvement in 1-year mortality prediction when compared to a standard FI alone among patients in the prefrail range. In contrast, we observed a modest (at least 4.1%) improvement in 1-year mortality prediction in the overall population. Enhancing AUC prediction for patients in the prefrail range is clinically important, as interventions that mitigate frailty may be most impactful in this population [<xref ref-type="bibr" rid="ref7">7</xref>]. Patients with prefrailty may benefit from interventions (eg, cardiac rehabilitation) that improve frailty status and cardiovascular outcomes [<xref ref-type="bibr" rid="ref1">1</xref>]. These findings enrich our understanding of the importance of FT in patients at lower FI levels, and a previous study compared the importance of FIs to that of FTs alone [<xref ref-type="bibr" rid="ref5">5</xref>]. These results may not generalize to nonveteran populations. The sample was predominately male but did include a diverse population in terms of race, ethnicity, and geographic distribution. In summary, methods for calculating frailty provide useful predictions of adverse outcomes among adults with HF. The addition of longitudinal frailty data improves predictions for patients with HF and prefrailty. These findings aid clinician and health system decision-making, as this population benefits most from interventions that slow or prevent frailty progression, and suggest that longitudinal data for modeling FT provide additional evidence for tailoring interventions to patients with HF who may benefit most from tailored interventions.</p></sec></body><back><ack><p>JR is supported by seed funding from Baylor College of Medicine, Houston, TX, United States; the Center for Innovations in Quality, Effectiveness and Safety (CIN 13&#x2013;413), Michael E. DeBakey VA Medical Center, Houston, TX, United States; and National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI) K25 funding (1K25HL152006-01). ARO is supported by VA Clinical Science Research &#x0026; Development Career Development Award Level 2 (award IK2-CX001800). MJH is supported by VA HSR CDA-2 award 1IK2HX003163-01A2.</p></ack><fn-group><fn fn-type="conflict"><p>None declared.</p></fn></fn-group><glossary><title>Abbreviations</title><def-list><def-item><term id="abb1">AUC</term><def><p>area under the curve</p></def></def-item><def-item><term id="abb2">FI</term><def><p>frailty index</p></def></def-item><def-item><term id="abb3">FT</term><def><p>frailty trajectory</p></def></def-item><def-item><term id="abb4">HF</term><def><p>heart failure</p></def></def-item><def-item><term id="abb5">VA</term><def><p>Veterans Health Administration</p></def></def-item></def-list></glossary><ref-list><title>References</title><ref id="ref1"><label>1</label><nlm-citation citation-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Ijaz</surname><given-names>N</given-names> </name><name name-style="western"><surname>Buta</surname><given-names>B</given-names> </name><name 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