Exercise Hemodynamics and Mitochondrial Oxidative Capacity in Disease Stages of Wild‐Type Transthyretin Amyloid Cardiomyopathy
Background Wild‐type transthyretin amyloid (ATTRwt) cardiomyopathy is increasingly recognized in the development of heart failure. The link between cardiac performance, hemodynamics, and mitochondrial function in disease stages of ATTRwt has not previously been studied but may provide new insights i...
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Wiley
2024-07-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.124.034213 |
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| author | Bertil Ladefoged Anders Dahl Pedersen Jacob Seefeldt Bent Roni Ranghøj Nielsen Hans Eiskjær Emil Lichscheidt Tor Clemmensen Julian David Gillmore Steen Hvitfeldt Poulsen |
| author_facet | Bertil Ladefoged Anders Dahl Pedersen Jacob Seefeldt Bent Roni Ranghøj Nielsen Hans Eiskjær Emil Lichscheidt Tor Clemmensen Julian David Gillmore Steen Hvitfeldt Poulsen |
| author_sort | Bertil Ladefoged |
| collection | DOAJ |
| description | Background Wild‐type transthyretin amyloid (ATTRwt) cardiomyopathy is increasingly recognized in the development of heart failure. The link between cardiac performance, hemodynamics, and mitochondrial function in disease stages of ATTRwt has not previously been studied but may provide new insights into the pathophysiology and clinical performance of the patients. Methods and Results The study investigated 47 patients diagnosed with ATTRwt at Aarhus University Hospital, Denmark. Patients were stratified according to the disease stages of the National Amyloidosis Centre (NAC) as NAC I with low levels of NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) (NAC I‐L, n=14), NAC I with high levels NT‐proBNP (NAC I‐H, n=20), and NAC II‐III (n=13). Exercise testing with simultaneous right heart catheterization was performed in all patients. Endomyocardial biopsies were collected from the patients and the mitochondrial oxidative phosphorylation capacity was assessed. All NAC disease groups, even in the NAC I‐L group, a significant abnormal increase in biventricular filling pressures were noted during exercise while the filling pressures was normal or near normal at rest. The inotropic response to exercise was reduced with diminished increase in cardiac output which was significantly more pronounced in the NAC I‐H (Diff. ‐2.4, 95% CI (−4.2: −0.7), P=0.00) and the NAC II‐III group (Diff: −3.1 L/min, 95% CI (−5.2: −1.1), P=0.00) compared with the NAC I‐L group. The pulmonary artery wedge pressure to cardiac output ratio at peak exercise was significantly different between NAC I‐L and NAC II‐III (Diff: 1.6 mm Hg*min/L, 95% CI (0.01:3.3, P=0.04)). Patients with ATTRwt had a reduced oxidative phosphorylation capacity which correlated to left ventricular mass but not to cardiac output capacity. Conclusions An abnormal restrictive left ventricle and right ventricle response to exercise was demonstrated, even present in patients with early‐stage ATTRwt. In more advanced disease stages a progressive impairment of the pressure‐flow relationship was noted. The myocyte energetics is deranged but not associated to the contractile reserve or restrictive filling characteristics in ATTRwt. |
| format | Article |
| id | doaj-art-36e4897fdd884b93ac55e5daa71d5e5b |
| institution | OA Journals |
| issn | 2047-9980 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | Wiley |
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| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-36e4897fdd884b93ac55e5daa71d5e5b2025-08-20T02:26:33ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-07-01131310.1161/JAHA.124.034213Exercise Hemodynamics and Mitochondrial Oxidative Capacity in Disease Stages of Wild‐Type Transthyretin Amyloid CardiomyopathyBertil Ladefoged0Anders Dahl Pedersen1Jacob Seefeldt2Bent Roni Ranghøj Nielsen3Hans Eiskjær4Emil Lichscheidt5Tor Clemmensen6Julian David Gillmore7Steen Hvitfeldt Poulsen8Department of Cardiology Aarhus University Hospital Aarhus DenmarkDepartment of Cardiology Aarhus University Hospital Aarhus DenmarkDepartment of Cardiology Aarhus University Hospital Aarhus DenmarkDepartment of Cardiology Aarhus University Hospital Aarhus DenmarkDepartment of Cardiology Aarhus University Hospital Aarhus DenmarkDepartment of Cardiology Aarhus University Hospital Aarhus DenmarkDepartment of Cardiology Aarhus University Hospital Aarhus DenmarkThe National Amyloidosis Centre, The Royal Free Hospital London UKDepartment of Cardiology Aarhus University Hospital Aarhus DenmarkBackground Wild‐type transthyretin amyloid (ATTRwt) cardiomyopathy is increasingly recognized in the development of heart failure. The link between cardiac performance, hemodynamics, and mitochondrial function in disease stages of ATTRwt has not previously been studied but may provide new insights into the pathophysiology and clinical performance of the patients. Methods and Results The study investigated 47 patients diagnosed with ATTRwt at Aarhus University Hospital, Denmark. Patients were stratified according to the disease stages of the National Amyloidosis Centre (NAC) as NAC I with low levels of NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) (NAC I‐L, n=14), NAC I with high levels NT‐proBNP (NAC I‐H, n=20), and NAC II‐III (n=13). Exercise testing with simultaneous right heart catheterization was performed in all patients. Endomyocardial biopsies were collected from the patients and the mitochondrial oxidative phosphorylation capacity was assessed. All NAC disease groups, even in the NAC I‐L group, a significant abnormal increase in biventricular filling pressures were noted during exercise while the filling pressures was normal or near normal at rest. The inotropic response to exercise was reduced with diminished increase in cardiac output which was significantly more pronounced in the NAC I‐H (Diff. ‐2.4, 95% CI (−4.2: −0.7), P=0.00) and the NAC II‐III group (Diff: −3.1 L/min, 95% CI (−5.2: −1.1), P=0.00) compared with the NAC I‐L group. The pulmonary artery wedge pressure to cardiac output ratio at peak exercise was significantly different between NAC I‐L and NAC II‐III (Diff: 1.6 mm Hg*min/L, 95% CI (0.01:3.3, P=0.04)). Patients with ATTRwt had a reduced oxidative phosphorylation capacity which correlated to left ventricular mass but not to cardiac output capacity. Conclusions An abnormal restrictive left ventricle and right ventricle response to exercise was demonstrated, even present in patients with early‐stage ATTRwt. In more advanced disease stages a progressive impairment of the pressure‐flow relationship was noted. The myocyte energetics is deranged but not associated to the contractile reserve or restrictive filling characteristics in ATTRwt.https://www.ahajournals.org/doi/10.1161/JAHA.124.034213cardiac amyloidosisinvasive hemodynamicsmitochondrial oxidative phosphorylationtransthyretin amyloid cardiomyopathy |
| spellingShingle | Bertil Ladefoged Anders Dahl Pedersen Jacob Seefeldt Bent Roni Ranghøj Nielsen Hans Eiskjær Emil Lichscheidt Tor Clemmensen Julian David Gillmore Steen Hvitfeldt Poulsen Exercise Hemodynamics and Mitochondrial Oxidative Capacity in Disease Stages of Wild‐Type Transthyretin Amyloid Cardiomyopathy Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease cardiac amyloidosis invasive hemodynamics mitochondrial oxidative phosphorylation transthyretin amyloid cardiomyopathy |
| title | Exercise Hemodynamics and Mitochondrial Oxidative Capacity in Disease Stages of Wild‐Type Transthyretin Amyloid Cardiomyopathy |
| title_full | Exercise Hemodynamics and Mitochondrial Oxidative Capacity in Disease Stages of Wild‐Type Transthyretin Amyloid Cardiomyopathy |
| title_fullStr | Exercise Hemodynamics and Mitochondrial Oxidative Capacity in Disease Stages of Wild‐Type Transthyretin Amyloid Cardiomyopathy |
| title_full_unstemmed | Exercise Hemodynamics and Mitochondrial Oxidative Capacity in Disease Stages of Wild‐Type Transthyretin Amyloid Cardiomyopathy |
| title_short | Exercise Hemodynamics and Mitochondrial Oxidative Capacity in Disease Stages of Wild‐Type Transthyretin Amyloid Cardiomyopathy |
| title_sort | exercise hemodynamics and mitochondrial oxidative capacity in disease stages of wild type transthyretin amyloid cardiomyopathy |
| topic | cardiac amyloidosis invasive hemodynamics mitochondrial oxidative phosphorylation transthyretin amyloid cardiomyopathy |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.124.034213 |
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