Do We Need Sex Specific HF Diagnostic Criteria in 2020?

Do We Need Sex Specific HF Diagnostic Criteria in 2020? Eileen O’Meara, M.D.CardiologistProfessor of MedicineMontreal Heart InstituteUniversitéde Montréal Conflict of Interest Disclosures•Grants/research support: HSFC grant for BioAIMI-HF (Biomarkers in Heart Failure of Ischemic Etiology)•Consultation and speaker fees paid to the MHI Research Center from: Amgen, Merck and Novartis•Consultation and speaker feesfrom: AstraZeneca, Bayer, BoehringerIngelheim.•Steering committee and National leader for clinical studies fees paid to my institution (MHI Research Center) from: American Regent, AstraZeneca, Cytokinetics, Merck and Novartis•Clinical trial participation: Amgen, Abbott, American Regent, AstraZeneca, Bayer, BoehringerIngelheim, Cytokinetics, Eidos, Novartis, Merck, Pfizer, Sanofi Learning Objectives•Describe between gender differences in HF risk profiles•Describe the differences between male and female with regards to HF phenotypes and outcomes•Understand that heart failure therapy response varies according to sex and LVEF Characteristics of Women and Men with HFpEF Tadic M et al. J. Clin. Med. 2019, 8, 792; doi:10.3390/jcm8060792 Circulation. 2018 April 24; 137(17): 1814–1823.doi:10.1161/CIRCULATIONAHA.117.031622 Risk of HF in Women Daubert MA, Douglas PS, JACC: Heart Failure Vol 7, No 3, 2019. Prevention of HF in Women Daubert MA, Douglas PS, JACC: Heart Failure Vol 7, No 3, 2019. CircHeart Fail. 2019;12:e006539.DOI: 10.1161/CIRCHEARTFAILURE. WHY?Cardiac structure, metabolism and functionHFpEFin Women Beale AL, et al. Circulation. 2018;138:198–205. Women predisposed to HFpEF:Comorbid Conditions Beale AL, et al. Circulation. 2018;138:198–205. Current Characteristics of Patients Hospitalized for HF Progress in CardiovascularDiseases, March 2020https://doi.org/10.1016/j.pcad.2020.03.013 Temporal Trends Current Characteristics of Patients Hospitalized for HF Progress in CardiovascularDiseases, March 2020https://doi.org/10.1016/j.pcad.2020.03.013 •“… Our data indicate an underuse of interventional treatments in women, although the beneficial impact of these treatments on survival are comparable between both sexes... •In accordance with our results, sex differences with regard to CRT utilization in patients hospitalized due to HF have been reported recently, demonstrating that women were less likely to receive CRT despite greater mortality risk reduction… “Progress in CardiovascularDiseases, March 2020https://doi.org/10.1016/j.pcad.2020.03.013 Heterogeneity in Multivariate AnalysisGender and Ejection Fraction in the PARAGON-HF trial Subgroup Overall Age (years) Less than 65 years 65 years or older Age (years) Less than 75 years 75 years or older Gender Male Female Race Caucasian Black Asian Other Region North America Latin America Western Europe Central Europe Asia/Pacific Diabetic Y es No LVEF at or below median (57%) above median (57%) History of AF Y es No Screening NT −proBNP at or below median (911pg/mL) above median (911pg/mL) Screening SBP at or below median (137mmHg) above median (137mmHg) MRA use Y es No Baseline eGFR <60 mL/min/1.73m2 >=60 mL/min/1.73m2 NYHA class I/II III/IV No. of Events/Patients 1903/4796 276/825 1627/3971 938/2597 965/2199 980/2317 923/2479 1542/3907 89/102 237/607 35/180 478/559 83/370 544/1390 466/1715 332/762 1041/2069 862/2727 1048/2495 855/2301 1140/2521 763/2275 708/2379 1183/2378 984/2450 919/2344 543/1238 1360/3558 1115/2341 787/2454 1402/3843 499/951 Hazard Ratio (95% CI) 0.87 (0.75 −1.01) 0.99 (0.64 −1.53) 0.85 (0.73 −0.99) 0.82 (0.66 −1.02) 0.92 (0.76 −1.11) 1.03 (0.85 −1.25) 0.73 (0.59 −0.90) 0.83 (0.71 −0.97) 0.69 (0.24 −1.99) 1.25 (0.87 −1.79) 1.03 (0.47 −2.28) 0.80 (0.57 −1.14) 1.33 (0.75 −2.36) 0.69 (0.53 −0.89) 0.97 (0.76 −1.24) 1.10 (0.79 −1.52) 0.89 (0.74 −1.09) 0.84 (0.68 −1.04) 0.78 (0.64 −0.95) 1.00 (0.81 −1.23) 0.83 (0.69 −1.00) 0.94 (0.75 −1.18) 0.85 (0.67 −1.08) 0.87 (0.73 −1.05) 0.88 (0.72 −1.07) 0.86 (0.69 −1.06) 0.73 (0.56 −0.94) 0.94 (0.79 −1.12) 0.79 (0.66 −0.95) 1.01 (0.80 −1.27) 0.90 (0.76 −1.06) 0.79 (0.59 −1.06) 0.4 0.6 0.8 1.0 2.0 Rate Ratio (95% CI) Subgroup Overall Age (years) Less than 65 years 65 years or older Age (years) Less than 75 years 75 years or older Gender Male Female Race Caucasian Black Asian Other Region North America Latin America Western Europe Central Europe Asia/Pacific Diabetic Y es No LVEF at or below median (57%) above median (57%) History of AF Y es No Screening NT −proBNP at or below median (911pg/mL) above median (911pg/mL) Screening SBP at or below median (137mmHg) above median (137mmHg) MRA use Y es No Baseline eGFR <60 mL/min/1.73m2 >=60 mL/min/1.73m2 NYHA class I/II III/IV No. of Events/Patients 1903/4796 276/825 1627/3971 938/2597 965/2199 980/2317 923/2479 1542/3907 89/102 237/607 35/180 478/559 83/370 544/1390 466/1715 332/762 1041/2069 862/2727 1048/2495 855/2301 1140/2521 763/2275 708/2379 1183/2378 984/2450 919/2344 543/1238 1360/3558 1115/2341 787/2454 1402/3843 499/951 Hazard Ratio (95% CI) 0.87 (0.75 −1.01) 0.99 (0.64 −1.53) 0.85 (0.73 −0.99) 0.82 (0.66 −1.02) 0.92 (0.76 −1.11) 1.03 (0.85 −1.25) 0.73 (0.59 −0.90) 0.83 (0.71 −0.97) 0.69 (0.24 −1.99) 1.25 (0.87 −1.79) 1.03 (0.47 −2.28) 0.80 (0.57 −1.14) 1.33 (0.75 −2.36) 0.69 (0.53 −0.89) 0.97 (0.76 −1.24) 1.10 (0.79 −1.52) 0.89 (0.74 −1.09) 0.84 (0.68 −1.04) 0.78 (0.64 −0.95) 1.00 (0.81 −1.23) 0.83 (0.69 −1.00) 0.94 (0.75 −1.18) 0.85 (0.67 −1.08) 0.87 (0.73 −1.05) 0.88 (0.72 −1.07) 0.86 (0.69 −1.06) 0.73 (0.56 −0.94) 0.94 (0.79 −1.12) 0.79 (0.66 −0.95) 1.01 (0.80 −1.27) 0.90 (0.76 −1.06) 0.79 (0.59 −1.06) 0.4 0.6 0.8 1.0 2.0 Rate Ratio (95% CI) Subgroup Overall Age (years) Less than 65 years 65 years or older Age (years) Less than 75 years 75 years or older Gender Male Female Race Caucasian Black Asian Other Region North America Latin America Western Europe Central Europe Asia/Pacific Diabetic Y es No LVEF at or below median (57%) above median (57%) History of AF Y es No Screening NT −proBNP at or below median (911pg/mL) above median (911pg/mL) Screening SBP at or below median (137mmHg) above median (137mmHg) MRA use Y es No Baseline eGFR <60 mL/min/1.73m2 >=60 mL/min/1.73m2 NYHA class I/II III/IV No. of Events/Patients 1903/4796 276/825 1627/3971 938/2597 965/2199 980/2317 923/2479 1542/3907 89/102 237/607 35/180 478/559 83/370 544/1390 466/1715 332/762 1041/2069 862/2727 1048/2495 855/2301 1140/2521 763/2275 708/2379 1183/2378 984/2450 919/2344 543/1238 1360/3558 1115/2341 787/2454 1402/3843 499/951 Hazard Ratio (95% CI) 0.87 (0.75 −1.01) 0.99 (0.64 −1.53) 0.85 (0.73 −0.99) 0.82 (0.66 −1.02) 0.92 (0.76 −1.11) 1.03 (0.85 −1.25) 0.73 (0.59 −0.90) 0.83 (0.71 −0.97) 0.69 (0.24 −1.99) 1.25 (0.87 −1.79) 1.03 (0.47 −2.28) 0.80 (0.57 −1.14) 1.33 (0.75 −2.36) 0.69 (0.53 −0.89) 0.97 (0.76 −1.24) 1.10 (0.79 −1.52) 0.89 (0.74 −1.09) 0.84 (0.68 −1.04) 0.78 (0.64 −0.95) 1.00 (0.81 −1.23) 0.83 (0.69 −1.00) 0.94 (0.75 −1.18) 0.85 (0.67 −1.08) 0.87 (0.73 −1.05) 0.88 (0.72 −1.07) 0.86 (0.69 −1.06) 0.73 (0.56 −0.94) 0.94 (0.79 −1.12) 0.79 (0.66 −0.95) 1.01 (0.80 −1.27) 0.90 (0.76 −1.06) 0.79 (0.59 −1.06) 0.4 0.6 0.8 1.0 2.0 Rate Ratio (95% CI) Primary endpoint Male980/23171.03 (0.85–1.25)0.73 (0.59–0.90) Sex Female923/2479 at or below median (57%)1048/24950.78 (0.64–0.95)1.00 (0.81–1.23) LVEF above median (57%)855/2301 Rate ratio (95% CI)0.40.60.81.02.0P = 0.002 (continuous)P = 0.03 (categorical) P < 0.006 Multivariable interaction p-valueRate ratio (95% CI)No. of events/patientsSubgroupOnly interactions for sex and ejection fraction remained nominally significant Solomon SD, et al. NEJM 2019 European Journal of Heart Failure, April 2020 So… Do We Need Sex Specific HF Diagnostic Criteria in 2020?•In my opinion, the DIAGNOSIS of HF should NOT differ based on GENDER•However, we DO need to better recognize that SEX-RELATED differences EXIST between women and men with HF:•Pathophysiology of HF, phenotypes and etiology•Comorbid conditions and CV risk factors differ between women and men•Access to CV/HF therapy and response to HF therapydiffer between women and men•Clinical outcomesdiffer between women and men (differences may vary depending on context –long-term/outpatients vs. acute/inpatients)•Studies on HF -population registries and clinical trials –should include enough women to allow for analyses that relate to sex-related differences•Our understanding of these gender differences is incomplete and should be improved