Trimetazidine in heart failure with preserved ejection fraction: a randomized controlled cross‐over trial
Abstract Aims Impaired myocardial energy homeostasis plays an import role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Left ventricular relaxation has a high energy demand, and left ventricular diastolic dysfunction has been related to impaired energy homeostasis...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-10-01
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| Series: | ESC Heart Failure |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ehf2.14418 |
| _version_ | 1797661485986480128 |
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| author | Arno A. van deBovenkamp Kiki T. J. Geurkink Frank T.P. Oosterveer Frances S. deMan Wouter E.M. Kok Patrick N.A. Bronzwaer Cor P. Allaart Aart J. Nederveen Albert C. vanRossum Adrianus J. Bakermans M. Louis Handoko |
| author_facet | Arno A. van deBovenkamp Kiki T. J. Geurkink Frank T.P. Oosterveer Frances S. deMan Wouter E.M. Kok Patrick N.A. Bronzwaer Cor P. Allaart Aart J. Nederveen Albert C. vanRossum Adrianus J. Bakermans M. Louis Handoko |
| author_sort | Arno A. van deBovenkamp |
| collection | DOAJ |
| description | Abstract Aims Impaired myocardial energy homeostasis plays an import role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Left ventricular relaxation has a high energy demand, and left ventricular diastolic dysfunction has been related to impaired energy homeostasis. This study investigated whether trimetazidine, a fatty acid oxidation inhibitor, could improve myocardial energy homeostasis and consequently improve exercise haemodynamics in patients with HFpEF. Methods and results The DoPING‐HFpEF trial was a phase II single‐centre, double‐blind, placebo‐controlled, randomized cross‐over trial. Patients were randomized to trimetazidine treatment or placebo for 3 months and switched after a 2‐week wash‐out period. The primary endpoint was change in pulmonary capillary wedge pressure, measured with right heart catheterization at multiple stages of bicycling exercise. Secondary endpoint was change in myocardial phosphocreatine/adenosine triphosphate, an index of the myocardial energy status, measured with phosphorus‐31 magnetic resonance spectroscopy. The study included 25 patients (10/15 males/females; mean (standard deviation) age, 66 (10) years; body mass index, 29.8 (4.5) kg/m2); with the diagnosis of HFpEF confirmed with (exercise) right heart catheterization either before or during the trial. There was no effect of trimetazidine on the primary outcome pulmonary capillary wedge pressure at multiple levels of exercise (mean change 0 [95% confidence interval, 95% CI −2, 2] mmHg over multiple levels of exercise, P = 0.60). Myocardial phosphocreatine/adenosine triphosphate in the trimetazidine arm was similar to placebo (1.08 [0.76, 1.76] vs. 1.30 [0.95, 1.86], P = 0.08). There was no change by trimetazidine compared with placebo in the exploratory parameters: 6‐min walking distance (mean change of −6 [95% CI −18, 7] m vs. −5 [95% CI −22, 22] m, respectively, P = 0.93), N‐terminal pro‐B‐type natriuretic peptide (5 (−156, 166) ng/L vs. −13 (−172, 147) ng/L, P = 0.70), overall quality‐of‐life (KCCQ and EQ‐5D‐5L, P = 0.78 and P = 0.51, respectively), parameters for diastolic function measured with echocardiography and cardiac magnetic resonance, or metabolic parameters. Conclusions Trimetazidine did not improve myocardial energy homeostasis and did not improve exercise haemodynamics in patients with HFpEF. |
| first_indexed | 2024-03-11T18:46:12Z |
| format | Article |
| id | doaj.art-f6813fa152f342c1953d0eb801a5665b |
| institution | Directory Open Access Journal |
| issn | 2055-5822 |
| language | English |
| last_indexed | 2024-03-11T18:46:12Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | ESC Heart Failure |
| spelling | doaj.art-f6813fa152f342c1953d0eb801a5665b2023-10-12T02:48:44ZengWileyESC Heart Failure2055-58222023-10-011052998301010.1002/ehf2.14418Trimetazidine in heart failure with preserved ejection fraction: a randomized controlled cross‐over trialArno A. van deBovenkamp0Kiki T. J. Geurkink1Frank T.P. Oosterveer2Frances S. deMan3Wouter E.M. Kok4Patrick N.A. Bronzwaer5Cor P. Allaart6Aart J. Nederveen7Albert C. vanRossum8Adrianus J. Bakermans9M. Louis Handoko10Department of Cardiology Amsterdam University Medical Centers, Vrije Universiteit Amsterdam Amsterdam The NetherlandsDepartment of Cardiology Amsterdam University Medical Centers, Vrije Universiteit Amsterdam Amsterdam The NetherlandsDepartment of Pulmonary Medicine Amsterdam University Medical Centers, Vrije Universiteit Amsterdam Amsterdam The NetherlandsAmsterdam Cardiovascular Sciences Amsterdam The NetherlandsAmsterdam Cardiovascular Sciences Amsterdam The NetherlandsDepartment of Cardiology Zaans Medical Center Zaandam The NetherlandsDepartment of Cardiology Amsterdam University Medical Centers, Vrije Universiteit Amsterdam Amsterdam The NetherlandsDepartment of Radiology and Nuclear Medicine Amsterdam University Medical Centers, University of Amsterdam Amsterdam The NetherlandsDepartment of Cardiology Amsterdam University Medical Centers, Vrije Universiteit Amsterdam Amsterdam The NetherlandsDepartment of Radiology and Nuclear Medicine Amsterdam University Medical Centers, University of Amsterdam Amsterdam The NetherlandsDepartment of Cardiology Amsterdam University Medical Centers, Vrije Universiteit Amsterdam Amsterdam The NetherlandsAbstract Aims Impaired myocardial energy homeostasis plays an import role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Left ventricular relaxation has a high energy demand, and left ventricular diastolic dysfunction has been related to impaired energy homeostasis. This study investigated whether trimetazidine, a fatty acid oxidation inhibitor, could improve myocardial energy homeostasis and consequently improve exercise haemodynamics in patients with HFpEF. Methods and results The DoPING‐HFpEF trial was a phase II single‐centre, double‐blind, placebo‐controlled, randomized cross‐over trial. Patients were randomized to trimetazidine treatment or placebo for 3 months and switched after a 2‐week wash‐out period. The primary endpoint was change in pulmonary capillary wedge pressure, measured with right heart catheterization at multiple stages of bicycling exercise. Secondary endpoint was change in myocardial phosphocreatine/adenosine triphosphate, an index of the myocardial energy status, measured with phosphorus‐31 magnetic resonance spectroscopy. The study included 25 patients (10/15 males/females; mean (standard deviation) age, 66 (10) years; body mass index, 29.8 (4.5) kg/m2); with the diagnosis of HFpEF confirmed with (exercise) right heart catheterization either before or during the trial. There was no effect of trimetazidine on the primary outcome pulmonary capillary wedge pressure at multiple levels of exercise (mean change 0 [95% confidence interval, 95% CI −2, 2] mmHg over multiple levels of exercise, P = 0.60). Myocardial phosphocreatine/adenosine triphosphate in the trimetazidine arm was similar to placebo (1.08 [0.76, 1.76] vs. 1.30 [0.95, 1.86], P = 0.08). There was no change by trimetazidine compared with placebo in the exploratory parameters: 6‐min walking distance (mean change of −6 [95% CI −18, 7] m vs. −5 [95% CI −22, 22] m, respectively, P = 0.93), N‐terminal pro‐B‐type natriuretic peptide (5 (−156, 166) ng/L vs. −13 (−172, 147) ng/L, P = 0.70), overall quality‐of‐life (KCCQ and EQ‐5D‐5L, P = 0.78 and P = 0.51, respectively), parameters for diastolic function measured with echocardiography and cardiac magnetic resonance, or metabolic parameters. Conclusions Trimetazidine did not improve myocardial energy homeostasis and did not improve exercise haemodynamics in patients with HFpEF.https://doi.org/10.1002/ehf2.14418Diastolic heart failureExercise toleranceHeart mitochondriaMetabolismPulmonary wedge pressureSwan–Ganz catheterization |
| spellingShingle | Arno A. van deBovenkamp Kiki T. J. Geurkink Frank T.P. Oosterveer Frances S. deMan Wouter E.M. Kok Patrick N.A. Bronzwaer Cor P. Allaart Aart J. Nederveen Albert C. vanRossum Adrianus J. Bakermans M. Louis Handoko Trimetazidine in heart failure with preserved ejection fraction: a randomized controlled cross‐over trial ESC Heart Failure Diastolic heart failure Exercise tolerance Heart mitochondria Metabolism Pulmonary wedge pressure Swan–Ganz catheterization |
| title | Trimetazidine in heart failure with preserved ejection fraction: a randomized controlled cross‐over trial |
| title_full | Trimetazidine in heart failure with preserved ejection fraction: a randomized controlled cross‐over trial |
| title_fullStr | Trimetazidine in heart failure with preserved ejection fraction: a randomized controlled cross‐over trial |
| title_full_unstemmed | Trimetazidine in heart failure with preserved ejection fraction: a randomized controlled cross‐over trial |
| title_short | Trimetazidine in heart failure with preserved ejection fraction: a randomized controlled cross‐over trial |
| title_sort | trimetazidine in heart failure with preserved ejection fraction a randomized controlled cross over trial |
| topic | Diastolic heart failure Exercise tolerance Heart mitochondria Metabolism Pulmonary wedge pressure Swan–Ganz catheterization |
| url | https://doi.org/10.1002/ehf2.14418 |
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