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Canadian Journal of Cardiology

Should We Be Using Sex-Specific Heart Failure Risk Scores?

Published:October 08, 2019DOI:https://doi.org/10.1016/j.cjca.2019.10.001
      When applied in the appropriate clinical setting, validated prognostic risk models provide a method to quantify and convey survival prospects to patients and care providers, and may help in decision making and directing care. Their use is endorsed by the most recent iteration of the Canadian Cardiovascular Society Heart Failure (HF) Guidelines.
      • Ezekowitz J.A.
      • O’Meara E.
      • McDonald M.A.
      • et al.
      2017 comprehensive update of the Canadian Cardiovascular Society Guidelines for the management of heart failure.
      Although many risk scores have been published for patients in various stages of HF across multiple settings, the Seattle Heart Failure Model (SHFM)
      • Levy W.C.
      • Mozaffarian D.
      • Linker D.T.
      • et al.
      The Seattle Heart Failure Model: prediction of survival in heart failure.
      and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC)
      • Pocock S.J.
      • Ariti C.A.
      • McMurray J.J.V.
      • et al.
      Predicting survival in heart failure: a risk score based on 39 372 patients from 30 studies.
      scores are two of the mostly widely used risk scores for ambulatory patients with HF. However, prognostic models in other cardiac diseases demonstrate the importance of taking pause before wider application; this may certainly be the case in HF. For instance, risk scores for predicting coronary artery disease have required recalibration to maintain accuracy among various demographic subgroups,
      • D’Agostino R.B.
      • Grundy S.
      • Sullivan L.M.
      • Wilson P.
      CHD Risk Prediction Group
      Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups investigation.
      or necessitated separate variable sets in predictive models when applied specifically to women.
      • Ridker P.M.
      • Buring J.E.
      • Rifai N.
      • Cook N.R.
      Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score.
      In HF, men and women also have significantly different etiologies and phenotypes of HF, as well as different demographics at the time of diagnosis.
      • Senni M.
      • Tribouilloy C.M.
      • Rodeheffer R.J.
      • et al.
      Congestive heart failure in the community: a study of all incident cases in Olmsted County, Minnesota, in 1991.
      • Simon T.
      • Mary-Krause M.
      • Funck-Brentano C.
      • Jaillon P.
      Sex differences in the prognosis of congestive heart failure: results from the Cardiac Insufficiency Bisoprolol Study (CIBIS II).
      • Cowie M.R.
      • Wood D.A.
      • Coats A.J.
      • et al.
      Incidence and aetiology of heart failure; a population-based study.
      • Kajimoto K.
      • Minami Y.
      • Otsubo S.
      • Sato N.
      investigators of the Acute Decompensated Heart Failure Syndromes (ATTEND) Registry. Sex differences in left ventricular cavity dilation and outcomes in acute heart failure patients with left ventricular systolic dysfunction.
      Furthermore, in those with reduced ejection fraction (HFrEF), female sex is a significant predictor of improved survival.
      • Simon T.
      • Mary-Krause M.
      • Funck-Brentano C.
      • Jaillon P.
      Sex differences in the prognosis of congestive heart failure: results from the Cardiac Insufficiency Bisoprolol Study (CIBIS II).
      ,
      • Adams K.F.
      • Sueta C.A.
      • Gheorghiade M.
      • et al.
      Gender differences in survival in advanced heart failure: insights from the FIRST study.
      Because the SHFM and MAGGIC scores were derived and validated in cohorts including a majority of male members, there remains a possibility that these scores inaccurately or differentially predict risk among women.
      In this issue of the Canadian Journal of Cardiology, Vishram-Nielsen et al.
      • Vishram-Nielsen J.K.K.
      • Foroutan F.
      • Ross H.J.
      • Gustafsson F.
      • Alba A.C.
      Performance of prognostic risk scores in heart failure patients: do sex differences exist?.
      set out to examine the predictive performance of the SHFM and MAGGIC scores separately in men and women using a retrospective cohort of ambulatory patients with HFrEF recruited from the Heart Function Clinic at Toronto General Hospital. Their analyses reveal that, overall, the SHFM and MAGGIC scores had similar discriminatory capacity and provided similar predicted vs observed risk between sexes, both for mortality and for a composite endpoint of mortality, implantation of a ventricular assist device, or transplantation. Among women specifically, both scores showed no significant difference between predicted and observed mortality for 1-year survival or for the composite outcome, but both scores significantly overestimated mortality at 3 years. In contrast, only the MAGGIC risk score significantly overestimated mortality in men at 3 years. Importantly, the MAGGIC score provided better risk classification than the SHFM of patients among both sexes, reclassifying 3% of women at 1 year and 3 years of follow-up, and 16% and 20% of men at 1 year and 3 years of follow-up, respectively.
      This demonstration of the robustness of common HF predictive models among both men and women is important to justify their continued use across sexes. Furthermore, although the SHFM and MAGGIC scores demonstrated superior metrics of accuracy or validity to the other at certain time periods, the MAGGIC score did prove to more accurately reclassify men and women at various times of follow-up compared with the SHFM.
      Several limitations to Vishram-Nielsen et al.’s study should be noted. Although both the SFHM and MAGGIC scores were originally derived from cohorts that included patients with mid-range and/or preserved ejection fraction (EF), Vishram-Nielsen et al. included only those with a left ventricular EF (LVEF) < 40%. Recent analyses of larger cohorts have suggested that the SHFM and MAGGIC scores remain similarly reliable in predicting mortality among those with preserved EF.
      • Rich J.D.
      • Burns J.
      • Freed B.H.
      • et al.
      Meta-Analysis Global Group in Chronic (MAGGIC) Heart Failure risk score: validation of a simple tool for the prediction of morbidity and mortality in heart failure with preserved ejection fraction.
      ,
      • Li S.
      • Marcus P.
      • Núñez J.
      • et al.
      Validity of the Seattle Heart Failure Model after heart failure hospitalization.
      Patients with recent hospitalizations were also excluded, though both scores have been validated and shown to retain similar accuracy among those with recent hospital admissions.
      • Rich J.D.
      • Burns J.
      • Freed B.H.
      • et al.
      Meta-Analysis Global Group in Chronic (MAGGIC) Heart Failure risk score: validation of a simple tool for the prediction of morbidity and mortality in heart failure with preserved ejection fraction.
      ,
      • Li S.
      • Marcus P.
      • Núñez J.
      • et al.
      Validity of the Seattle Heart Failure Model after heart failure hospitalization.
      In addition, more than 50% of patients had data missing for uric acid and total cholesterol, which are needed in the calculation of risk by the SFHM. Although imputing these variables for such a high proportion may affect the predictive accuracy of the SFHM in this cohort, the numerous studies in which these variables are frequently missing suggest that they may not be widely available.
      • Khanam S.S.
      • Choi E.
      • Son J.-W.
      • et al.
      Validation of the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) heart failure risk score and the effect of adding natriuretic peptide for predicting mortality after discharge in hospitalized patients with heart failure.
      ,
      • May H.T.
      • Horne B.D.
      • Levy W.C.
      • et al.
      Validation of the Seattle Heart Failure Model in a community-based heart failure population and enhancement by adding B-type natriuretic peptide.
      In light of the ongoing disparity between men and women in inclusion in major HF clinical trials,
      • Scott P.E.
      • Unger E.F.
      • Jenkins M.R.
      • et al.
      Participation of women in clinical trials supporting FDA approval of cardiovascular drugs.
      and in keeping with an emerging framework of sex-specific guidelines and recommendations,
      • Tannenbaum C.
      • Norris C.M.
      • McMurtry M.S.
      Sex-specific considerations in guidelines generation and application.
      it is imperative that any discussion about prognosis with female patients include objective measures of risk that are validated among women specifically. Vishram-Nielsen et al. are the first to demonstrate this with two widely used HF clinical prediction scores, while showing that the MAGGIC risk score may be superior to the SHFM due to better risk classification. Moving forward, as researchers and cardiologists, we should always endeavour to include patients from underrepresented vulnerable populations in studies so we can gather information applicable to a variety of groups and sexes. By including such patients and creating sex- and group-specific risk scores, we can provide tailored, evidence-based, and compassionate care to an increasingly diverse patient population.

      Funding Sources

      The authors report no funding sources.

      Disclosures

      The authors have no conflicts of interest to disclose.

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