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- Frisk, Christoffer, et al.
(författare)
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Cardiac biopsies reveal differences in transcriptomics between left and right ventricle in patients with or without diagnostic signs of heart failure
- 2024
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- New or mild heart failure (HF) is mainly caused by left ventricular dysfunction. We hypothesised that gene expression differ between the left (LV) and right ventricle (RV) and secondly by type of LV dysfunction. We compared gene expression through myocardial biopsies from LV and RV of patients undergoing elective coronary bypass surgery (CABG). Patients were categorised based on LV ejection fraction (EF), diastolic function and NT-proBNP into pEF (preserved; LVEF ≥ 45%), rEF (reduced; LVEF < 45%) or normal LV function. Principal component analysis of gene expression displayed two clusters corresponding to LV and RV. Up-regulated genes in LV included natriuretic peptides NPPA and NPPB, transcription factors/coactivators STAT4 and VGLL2, ion channel related HCN2 and LRRC38 associated with cardiac muscle contraction, cytoskeleton, and cellular component movement. Patients with pEF phenotype versus normal differed in gene expression predominantly in LV, supporting that diastolic dysfunction and structural changes reflect early LV disease in pEF. DKK2 was overexpressed in LV of HFpEF phenotype, potentially leading to lower expression levels of β-catenin, α-SMA (smooth muscle actin), and enhanced apoptosis, and could be a possible factor in the development of HFpEF. CXCL14 was down-regulated in both pEF and rEF, and may play a role to promote development of HF.
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| 2. |
- Fux, Thomas, et al.
(författare)
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Synthetic tracheal grafts seeded with bone marrow cells fail to generate functional tracheae : First long-term follow-up study
- 2020
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Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : MOSBY-ELSEVIER. - 0022-5223 .- 1097-685X. ; 159:6, s. 2525-2537.e23
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Synthetic tracheal grafts seeded with autologous bone marrow-mononuclear cells (BM-MNCs) have been described as becoming living and functional grafts representing a promising option for tracheal replacement for pathologies unamenable by segmental resection or autologous repair. This study aimed to present the first long-term follow-up of these procedures in humans.Methods: We retrospectively analyzed 3 patients who received synthetic tracheal grafts seeded with BM-MNCs implanted.Results: Patient 1 was a 37-year-old man with mucoepidermoid carcinoma, the first-ever human to receive a synthetic tracheal graft seeded with BM-MNCs. Patient 2 was a 30-year-old man with adenoid cystic carcinoma, and patient 3 was a 22-year-old woman with an iatrogenic tracheal injury. All patients developed graft-related complications necessitating multiple surgical reinterventions. Patient 1 was hospitalized for 8 months before dying from respiratory failure secondary to graft dehiscence 32 months after implantation. Patient 2 died 3.5 months after implantation from undisclosed causes. Patient 3 received a second synthetic tracheal graft after 11 months and an allogeneic trachea and lung transplantation 45 months after the primary implantation. Patient 3 underwent 191 surgical interventions after the primary implantation and spent 55 months in the intensive care unit before dying from airway bleeding. All patients' bronchoscopic, histologic, and radiologic investigations demonstrated graft-associated complications, including anastomotic fistulae and obstructive granulation tissue, without graft vascularization, mucosal lining, or integration into adjacent tissues.Conclusions: Synthetic tracheal grafts seeded with BM-MNCs do not become living functional tracheal grafts and lead to debilitating complications and death.
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| 3. |
- Kallonen, Janica, et al.
(författare)
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Quality of life and functional status after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension : A Swedish single-center study
- 2023
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Ingår i: Pulmonary Circulation. - : Wiley. - 2045-8932 .- 2045-8940. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about long-term quality of life (QOL) and functional status after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH). We investigated QOL and functional status late after PEA. All patients who underwent PEA for CTEPH 1993–2020 at one Swedish center were included. Baseline characteristics and data from right heart catheterization, 6-min walk test, and Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) were obtained from patient charts and national registers. The RAND 36-Item Health Survey was sent by post, and Karnofsky Performance Status (KPS) was evaluated by telephone. A total of 110 patients were included. The survey was completed by 49/66 (74%) patients who were alive in 2020. In all domains except for bodily pain, QOL was slightly lower than that of an age-matched reference population. The KPS score was obtained from 42/49 (86%) patients; of these, 31 patients (74%) had a KPS score of ≥80% (able to carry on normal activity). All 42 patients were able to live at home and care for personal needs. The median postoperative CAMPHOR scores were: 4 for symptoms, 4 for activity, and 2.5 for QOL. We observed that QOL after PEA approached the expected QOL in a reference population and that CAMPHOR scores were comparable to those of a large UK cohort after PEA. Functional status improved when assessed late after PEA. Three-quarters of the study population were able to conduct normal activities at late follow-up. Our findings suggest that many patients enjoy satisfactory QOL and high functional status late after PEA.
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| 4. |
- Matan, Dmitri, et al.
(författare)
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Extracellular vesicles in heart failure : A study in patients with heart failure with preserved ejection fraction or heart failure with reduced ejection fraction characteristics undergoing elective coronary artery bypass grafting
- 2022
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Ingår i: Frontiers in Cardiovascular Medicine. - : Frontiers Media S.A.. - 2297-055X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- AimsExtracellular vesicles (EVs) were investigated as potential biomarkers associated with heart failure (HF) pathophysiology in patients undergoing elective coronary artery bypass surgery characterized by HF phenotype. Materials and methodsPatients with preoperative proxy-diagnoses of HF types i.e., preserved (HFpEF; n = 19) or reduced ejection fraction (HFrEF; n = 20) were studied and compared to patients with normal left ventricular function (n = 42). EVs in plasma samples collected from the coronary sinus, an arterial line, and from the right atrium were analyzed by flow cytometry. We studied EVs of presumed cardiomyocyte origin [EVs exposing Connexin-43 + Caveolin-3 (Con43 + Cav3) and Connexin-43 + Troponin T (Con43 + TnT)], of endothelial origin [EVs exposing VE-Cadherin (VE-Cad)] and EVs exposing inflammatory markers [myeloperoxidase (MPO) or pentraxin3 (PTX3)]. ResultsMedian concentrations of EVs exposing Con43 + TnT and Con43 + Cav3 were approximately five to six times higher in coronary sinus compared to radial artery indicative of cardiac release. Patients with HFrEF had high trans-coronary gradients of both Con43 + TnT and Con43 + Cav3 EVs, whereas HFpEF had elevated gradients of Con43 + Cav3 EVs but lower gradients of Con43 + TnT. Coronary sinus concentrations of both Con43 + TnT and Con43 + Cav3 correlated significantly with echocardiographic and laboratory measures of HF. MPO-EV concentrations were around two times higher in the right atrium compared to the coronary sinus, and slightly higher in HFpEF than in HFrEF. EV concentrations of endothelial origin (VE-Cad) were similar in all three patient groups. ConclusionCon43 + TnT and Con43 + Cav3 EVs are released over the heart indicating cardiomyocyte origin. In HFrEF the EV release profile is indicative of myocardial injury and myocardial stress with elevated trans-coronary gradients of both Con43 + TnT and Con43 + Cav3 EVs, whereas in HFpEF the profile indicates myocardial stress with less myocardial injury.
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