Abstract 980 Relevance of heart rate recovery for individuals with heart failure

Background: Heart rate recovery (HRR) is cardiac measure of autonomic dysfunction (AD). A Decreased HRR has been reported to be associated with all-cause mortality in heart failure (HF) patients. However, the predictive value of HRR for HF-specific clinical outcome is not yet understood.

Methods: Data of the MyoVasc study (N=3,289), a prospective cohort study on chronic HF (NCT04064450), were analyzed. Participants underwent a 5 hour highly standardized examination at a dedicated study center including cardiopulmonary exercise testing (CPET). CPET was performed on a bicycle ergometer according to an adjusted WHO protocol. HF was classified according to the Universal Definition of HF. Medication affecting HRR₆₀ and clinical determinants of HRR₆₀ were identified in regression analyses and subsequently considered as covariates in outcome analyses. To analyze HF-specific outcome, worsening of HF defined as a composite of cardiac death, HF hospitalization and ambulatory worsening requiring medical therapy, was analyzed as primary study endpoint. Information on clinical outcome was derived from structured follow-up with subsequent validation via source data and independent adjudication of clinical endpoints.

Results: The analysis sample comprised N=1,288 individuals with available information on HRR₆₀ (mean age: 65.0±10.4 years, female sex: 28.2%) ranging from HF stage B to D. In univariate analysis, worse HRR₆₀ was associated with higher levels of NT-proBNP (P for trend <0.0001). In multivariable regression analysis, the following clinical determinants associated with HRR₆₀ were identified: age (β-estimate -0.17 (95% confidence interval (CI) -0.22; -0.12), P<0.0001), female sex (β-estimate: -0.17 (95%CI -0.28; -0.06), P=0.003), diabetes mellitus (β-estimate: -0.16 (95%CI -0.28; -0.03), P<0.012), smoking (β-estimate: -0.30 (95%CI -0.41; -0.18) P<0.0001), obesity (β-estimate: -0.23 (95%CI -0.33, -0.12), P<0.0001), history of stroke (β-estimate: -0.21 (95%CI -0.38; -0.04), P=0.014), peripheral artery disease (β-estimate -0.34 (95%CI -0.54; -0.14), P=0.00081), and chronic kidney disease (β-estimate: -0.28 (95% CI: -0.42; -0.14), P<0.0001). In Cox regression analyses HRR₆₀ was identified as an independent predictor of clinical outcome as reflected by all-cause death (HR_{log(HRR60)[per -1SD]}: 1.53 (95%CI 1.27; 1.86), P<0.0001) and worsening of HF (HR_{log(HRR60)[per -1SD]}1.20 (95%CI 1.05; 1.47), P=0.012) independent of age, sex, clinical determinants and medication. Further analysis revealed that HRR₆₀ was a robust predictor of outcome after adjustment for age, sex and NT-proBNP. Sensitivity analysis demonstrated that HRR₆₀ was predictive for worsening of HF for both individuals with preserved ejection fraction (HFpEF) (HR_{log(HRR60)[per -1SD]}1.66 (95%CI 1.29; 2.15), P=0.0001) (HF stage C/D, LVEF≥50%) and reduced ejection fraction (HFrEF) (HR_{log(HRR60)[per -1SD]}1.22 (95%CI 1.05; 1.42); P=0.01) (HF stage C/D, LVEF<50%) as well as for all-cause mortality (HFrEF: HR_{log(HRR60)[per -1SD]}1.51 (95%CI 1.18; 1.93), P=0.001; HFpEF: HR_{log(HRR60)[per -1SD]}2.04 (95%CI 1.51; 2.77), P<0.0001).

Conclusion: In the present study, HRR₆₀ was identified as a strong predictor of clinical outcome in individuals with HF, irrespective of the HF phenotype and independent of a large set of confounders including NT-proBNP. This underlines the relevance of HRR as a proxy for AD for the clinical course of HF with potential implications for risk stratification and intervention.

Clin Res Cardiol (2022). https://doi.org/10.1007/s00392-022-02002-5
Relevance of heart rate recovery for individuals with heart failure – Results from the MyoVasc study
D. Velmeden¹, J. Söhne¹, A. Schuch¹, S. Zeid², A. Schulz², S.-O. Tröbs³, F. Müller¹, M. Heidorn¹, G. Buch², W. Dinh⁴, K. Lackner⁵, T. Gori³, T. Münzel¹, P. S. Wild², J. Prochaska³, für die Studiengruppe: DZHK
¹Kardiologie 1, Zentrum für Kardiologie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz; ²Präventive Kardiologie und Medizinische Prävention, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz; ³Zentrum für Kardiologie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz; ⁴Research & Early Development, Clinical Experimentation CV, BAYER AG, Wuppertal; ⁵Institut für Klinische Chemie und Laboratoriumsmedizin, Universitätsmedizin der Johannes Gutenberg Universität Mainz, Mainz;
Background: Heart rate recovery (HRR) is cardiac measure of autonomic dysfunction (AD). A Decreased HRR has been reported to be associated with all-cause mortality in heart failure (HF) patients. However, the predictive value of HRR for HF-specific clinical outcome is not yet understood. Methods: Data of the MyoVasc study (N=3,289), a prospective cohort study on chronic HF (NCT04064450), were analyzed. Participants underwent a 5 hour highly standardized examination at a dedicated study center including cardiopulmonary exercise testing (CPET). CPET was performed on a bicycle ergometer according to an adjusted WHO protocol. HF was classified according to the Universal Definition of HF. Medication affecting HRR₆₀ and clinical determinants of HRR₆₀ were identified in regression analyses and subsequently considered as covariates in outcome analyses. To analyze HF-specific outcome, worsening of HF defined as a composite of cardiac death, HF hospitalization and ambulatory worsening requiring medical therapy, was analyzed as primary study endpoint. Information on clinical outcome was derived from structured follow-up with subsequent validation via source data and independent adjudication of clinical endpoints. Results: The analysis sample comprised N=1,288 individuals with available information on HRR₆₀ (mean age: 65.0±10.4 years, female sex: 28.2%) ranging from HF stage B to D. In univariate analysis, worse HRR₆₀ was associated with higher levels of NT-proBNP (P for trend <0.0001). In multivariable regression analysis, the following clinical determinants associated with HRR₆₀ were identified: age (β-estimate -0.17 (95% confidence interval (CI) -0.22; -0.12), P<0.0001), female sex (β-estimate: -0.17 (95%CI -0.28; -0.06), P=0.003), diabetes mellitus (β-estimate: -0.16 (95%CI -0.28; -0.03), P<0.012), smoking (β-estimate: -0.30 (95%CI -0.41; -0.18) P<0.0001), obesity (β-estimate: -0.23 (95%CI -0.33, -0.12), P<0.0001), history of stroke (β-estimate: -0.21 (95%CI -0.38; -0.04), P=0.014), peripheral artery disease (β-estimate -0.34 (95%CI -0.54; -0.14), P=0.00081), and chronic kidney disease (β-estimate: -0.28 (95% CI: -0.42; -0.14), P<0.0001). In Cox regression analyses HRR₆₀ was identified as an independent predictor of clinical outcome as reflected by all-cause death (HR_{log(HRR60)[per -1SD]}: 1.53 (95%CI 1.27; 1.86), P<0.0001) and worsening of HF (HR_{log(HRR60)[per -1SD]}1.20 (95%CI 1.05; 1.47), P=0.012) independent of age, sex, clinical determinants and medication. Further analysis revealed that HRR₆₀ was a robust predictor of outcome after adjustment for age, sex and NT-proBNP. Sensitivity analysis demonstrated that HRR₆₀ was predictive for worsening of HF for both individuals with preserved ejection fraction (HFpEF) (HR_{log(HRR60)[per -1SD]}1.66 (95%CI 1.29; 2.15), P=0.0001) (HF stage C/D, LVEF≥50%) and reduced ejection fraction (HFrEF) (HR_{log(HRR60)[per -1SD]}1.22 (95%CI 1.05; 1.42); P=0.01) (HF stage C/D, LVEF<50%) as well as for all-cause mortality (HFrEF: HR_{log(HRR60)[per -1SD]}1.51 (95%CI 1.18; 1.93), P=0.001; HFpEF: HR_{log(HRR60)[per -1SD]}2.04 (95%CI 1.51; 2.77), P<0.0001). Conclusion: In the present study, HRR₆₀ was identified as a strong predictor of clinical outcome in individuals with HF, irrespective of the HF phenotype and independent of a large set of confounders including NT-proBNP. This underlines the relevance of HRR as a proxy for AD for the clinical course of HF with potential implications for risk stratification and intervention.
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