Toru Suzuki1, Yoshiyuki Yazaki1, Adriaan A Voors2, Donald J L Jones1,3, Daniel C S Chan1, Stefan D Anker4,5, John G Cleland6, Kenneth Dickstein7,8, Gerasimos Filippatos9, Hans L Hillege2, Chim C Lang10, Piotr Ponikowski11, Nilesh J Samani1, Dirk J van Veldhuisen2, Faiez Zannad12, Aeilko H Zwinderman13, Marco Metra14, Leong L Ng1. 1. Department of Cardiovascular Sciences, University of Leicester, Leicester, NIHR Leicester Biomedical Research Centre, Leicester, UK. 2. Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 3. Department of Cancer Studies, University of Leicester, Leicester Royal Infirmary, Leicester, UK. 4. Division of Cardiology and Metabolism - Heart Failure, Cachexia & Sarcopenia, Department of Cardiology (CVK); and Berlin-Brandenburg Center for Regenerative Therapies (BCRT); Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK) Berlin, Charité Universitätsmedizin Berlin, Germany. 5. Department of Cardiology and Pneumology, University Medical Center Göttingen (UMG), Göttingen, Germany. 6. National Heart & Lung Institute, Royal Brompton and Harefield Hospitals, Imperial College, London, UK. 7. University of Bergen, Bergen, Norway. 8. Stavanger University Hospital, Stavanger, Norway. 9. National and Kapodistrian University of Athens, School of Medicine, Department of Cardiology, Heart Failure Unit, Athens University Hospital Attikon, Athens, Greece. 10. School of Medicine Centre for Cardiovascular and Lung Biology, Division of Medical Sciences, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK. 11. Department of Heart Diseases, Wroclaw Medical University, Poland, and Cardiology Department, Military Hospital, Wroclaw, Poland. 12. Inserm CIC 1433, Université de Lorraine, CHU de Nancy, Nancy, France. 13. Department of Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, Amsterdam, The Netherlands. 14. Institute of Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
Abstract
AIMS: Association of elevated circulating levels of trimethylamine N-oxide (TMAO) with adverse outcomes in patients with heart failure (HF) has been described. However, response of TMAO levels to treatment and medications has not been investigated. Therefore, we investigated whether TMAO levels are responsive to guideline-recommended treatment and medications, and further reflect changes in outcomes. METHODS AND RESULTS: TMAO levels were investigated in the systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF), which addressed response to guideline-recommended pharmacological treatment. TMAO levels in 2234 patients with new-onset or progressively worsening HF showed strong associations with adverse events (mortality and/or rehospitalisation) at 1, 2 and 3 years [hazard ratio (HR) 1.37-1.51, P ≤ 0.019). Analysis of 972 patients with plasma available at both enrolment and follow-up visit showed reductions of B-type natriuretic peptide (BNP) levels with guideline-based treatment (P < 0.001), but not for TMAO levels. Moreover, patients with higher TMAO levels than median before and after treatment showed increased association with adverse outcomes [HR 2.21, 95% confidence interval (CI) 1.43-3.43, P < 0.001] compared to patients with lower than median levels either before or after treatment (HR 1.13, 95% CI 0.63-2.04, P = 0.684 and HR 1.14, 95% CI 0.64-2.03, P = 0.662, respectively). CONCLUSION: TMAO levels were associated with adverse outcomes (mortality and/or rehospitalisation) in BIOSTAT-CHF, and did not respond to guideline-based pharmacological treatment in contrast to BNP levels which did as expected. Lower TMAO levels were associated with favourable outcome regardless of treatment.
AIMS: Association of elevated circulating levels of trimethylamine N-oxide (TMAO) with adverse outcomes in patients with heart failure (HF) has been described. However, response of TMAO levels to treatment and medications has not been investigated. Therefore, we investigated whether TMAO levels are responsive to guideline-recommended treatment and medications, and further reflect changes in outcomes. METHODS AND RESULTS:TMAO levels were investigated in the systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF), which addressed response to guideline-recommended pharmacological treatment. TMAO levels in 2234 patients with new-onset or progressively worsening HF showed strong associations with adverse events (mortality and/or rehospitalisation) at 1, 2 and 3 years [hazard ratio (HR) 1.37-1.51, P ≤ 0.019). Analysis of 972 patients with plasma available at both enrolment and follow-up visit showed reductions of B-type natriuretic peptide (BNP) levels with guideline-based treatment (P < 0.001), but not for TMAO levels. Moreover, patients with higher TMAO levels than median before and after treatment showed increased association with adverse outcomes [HR 2.21, 95% confidence interval (CI) 1.43-3.43, P < 0.001] compared to patients with lower than median levels either before or after treatment (HR 1.13, 95% CI 0.63-2.04, P = 0.684 and HR 1.14, 95% CI 0.64-2.03, P = 0.662, respectively). CONCLUSION:TMAO levels were associated with adverse outcomes (mortality and/or rehospitalisation) in BIOSTAT-CHF, and did not respond to guideline-based pharmacological treatment in contrast to BNP levels which did as expected. Lower TMAO levels were associated with favourable outcome regardless of treatment.
Authors: Melana Yuzefpolskaya; Bruno Bohn; Paolo C Colombo; Ryan T Demmer; Azka Javaid; Giulio M Mondellini; Lorenzo Braghieri; Alberto Pinsino; Duygu Onat; Barbara Cagliostro; Andrea Kim; Koji Takeda; Yoshifumi Naka; Maryjane Farr; Gabriel T Sayer; Nir Uriel; Renu Nandakumar; Sumit Mohan Journal: Circ Heart Fail Date: 2021-06-15 Impact factor: 10.447