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M. Heidorn1, A. Schuch1, F. Müller1, S.-O. Tröbs1, G. Buch2, A. Schulz2, S. Schwuchow-Thonke1, D. Velmeden1, K. Strauch3, I. Schmidtmann1, K. J. Lackner1, T. Gori3, T. Münzel1, J. Prochaska3, P. S. Wild2, für die Studiengruppe: DZHK
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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;
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Background: Chronic obstructive pulmonary disease (COPD) is an established predictor of clinical outcome in heart failure, but little is known about pulmonary restriction as previous studies focused on spirometry, which can only estimate total lung capacity (TLC). Given this background, this study aimed to investigate the predictive role of pulmonary restriction in chronic heart failure (HF).
Methods: Data of the MyoVasc study (NCT04064450), a cohort study on HF, were analyzed. Information on pulmonary function was obtained via body plethysmography and spirometry during a detailed medical-technical examination in a dedicated study center. Subjects with TLC < 80 [% predicted] were categorized as restrictive and forced expiratory ratio < 0.7 or prevalent COPD served as criteria for categorization of obstruction. For the present analysis HF and HF-phenotypes were defined according to current guidelines of the American Heart Association (AHA). Structured follow-up investigation ascertained information on clinical outcome. The primary study endpoint was worsening of heart failure defined as composite of HF-hospitalization and cardiac death.
Results: In total, 1,509 participants with HF and complete information on pulmonary function were available for analysis. The mean age of the analysis sample was 67.5 ± 9.9 years, 33.8 % were women, N=124 participants had a restrictive, and N=400 an obstructive airway pattern. Heart failure with preserved ejection fraction (HFpEF) was present in 561 subjects, 336 participants had HFpEFborderline, and 290 individuals HF with reduced ejection fraction (HFrEF). In cumulative incidence plots pulmonary restriction and obstruction were related to a higher event incidence of worsening of HF compared to normal pulmonary function, with the largest effect in the restriction group. In order to investigate whether this relationship is independent of potential effect confounders, Cox-competing risk analyses were performed: under adjustment for age, sex and height, pulmonary restriction (Hazard ratio (HR) 2.05, 95 % confidence interval (CI) 1.35–3.11, P<0.001) and obstruction (HR 1.52, 95%CI 1.10-2.11, P=0.01) predicted worsening of heart failure. After additional controlling for cardiovascular risk factors and comorbidities only the relationship between restriction and worsening of HF remained independently associated in the total sample (HRrestriction 1.69, 1.08-2.63, P=0.02; HRobstruction 1.34, 95%CI 0.95-1.87, P=0.09). In this fully adjusted model both pulmonary phenotypes were stronger related to cardiac death (HRrestriction 3.25, 1.70-6.25, P<0.001; HRobstruction 1.81, 95%CI 1.02-3.24, P=0.04) than to HF-hospitalization (HRrestriction 1.40, 0.83-3.27, P=0.2; HRobstruction 1.38, 95%CI 0.96-1.98, P=0.08). Sensitivity analysis among HF-phenotypes revealed pulmonary restriction as a specific predictor for worsening of HF in HFpEF (HR 2.61, 95%CI 1.13-6.02, P=0.02), and HFpEFborderline (HR 3.31, 95%CI 1.65-6.67, P<0.001), while no relevant impact was observed in HFrEF (HR 0.99, 95%CI 0.49-2.00, P=1.0). No relevant relationship between pulmonary obstruction and clinical outcome was observed across HF-phenotypes.
Conclusion: Pulmonary restriction is a stronger predictor of disease progression in chronic HF than obstructive pulmonary disorders such as COPD. The predictive role of a reduced TLC is specific for HFpEF and HFpEFborderline indicating a particular role in the pathophysiology in these phenotypes of HF.
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