| 1. |
- Egerstedt, Anna, et al.
(författare)
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Profiling of the plasma proteome across different stages of human heart failure
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 5830-
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure (HF) is a major public health problem characterized by inability of the heart to maintain sufficient output of blood. The systematic characterization of circulating proteins across different stages of HF may provide pathophysiological insights and identify therapeutic targets. Here we report application of aptamer-based proteomics to identify proteins associated with prospective HF incidence in a population-based cohort, implicating modulation of immunological, complement, coagulation, natriuretic and matrix remodeling pathways up to two decades prior to overt disease onset. We observe further divergence of these proteins from the general population in advanced HF, and regression after heart transplantation. By leveraging coronary sinus samples and transcriptomic tools, we describe likely cardiac and specific cellular origins for several of the proteins, including Nt-proBNP, thrombospondin-2, interleukin-18 receptor, gelsolin, and activated C5. Our findings provide a broad perspective on both cardiac and systemic factors associated with HF development.
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| 2. |
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| 3. |
- Wells, Quinn S., et al.
(författare)
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Accelerating Biomarker Discovery Through Electronic Health Records, Automated Biobanking, and Proteomics
- 2019
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 73:17, s. 2195-2205
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Tidskriftsartikel (refereegranskat)abstract
- Background: Circulating biomarkers can facilitate diagnosis and risk stratification for complex conditions such as heart failure (HF). Newer molecular platforms can accelerate biomarker discovery, but they require significant resources for data and sample acquisition. Objectives: The purpose of this study was to test a pragmatic biomarker discovery strategy integrating automated clinical biobanking with proteomics. Methods: Using the electronic health record, the authors identified patients with and without HF, retrieved their discarded plasma samples, and screened these specimens using a DNA aptamer-based proteomic platform (1,129 proteins). Candidate biomarkers were validated in 3 different prospective cohorts. Results: In an automated manner, plasma samples from 1,315 patients (31% with HF) were collected. Proteomic analysis of a 96-patient subset identified 9 candidate biomarkers (p < 4.42 × 10 −5 ). Two proteins, angiopoietin-2 and thrombospondin-2, were associated with HF in 3 separate validation cohorts. In an emergency department–based registry of 852 dyspneic patients, the 2 biomarkers improved discrimination of acute HF compared with a clinical score (p < 0.0001) or clinical score plus B-type natriuretic peptide (p = 0.02). In a community-based cohort (n = 768), both biomarkers predicted incident HF independent of traditional risk factors and N-terminal pro–B-type natriuretic peptide (hazard ratio per SD increment: 1.35 [95% confidence interval: 1.14 to 1.61; p = 0.0007] for angiopoietin-2, and 1.37 [95% confidence interval: 1.06 to 1.79; p = 0.02] for thrombospondin-2). Among 30 advanced HF patients, concentrations of both biomarkers declined (80% to 84%) following cardiac transplant (p < 0.001 for both). Conclusions: A novel strategy integrating electronic health records, discarded clinical specimens, and proteomics identified 2 biomarkers that robustly predict HF across diverse clinical settings. This approach could accelerate biomarker discovery for many diseases.
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| 4. |
- Zar, Gustav, et al.
(författare)
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Whole-genome sequencing based on formalin-fixed paraffin-embedded endomyocardial biopsies for genetic studies on outcomes after heart transplantation
- 2019
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Whole-genome sequencing (WGS) of heart transplant recipient- and donor-derived cardiac biopsies may facilitate organ matching, graft failure prediction, and immunotolerance research. The objective of this study was to determine the feasibility of WGS based on formalin-fixed paraffin-embedded endomyocardial biopsies. Methods and results The study included serial donor- and recipient samples from patients who had undergone heart transplantation at Skane University Hospital, Lund, Sweden, between 1988 and 2009. DNA extraction and WGS were conducted. Additional WGS sequencing quality metrics and coverage were obtained with the Genome Analysis Toolkit (GATK). 455 endomyocardial samples from 37 heart transplant recipients were acquired from routine rejection monitoring and stored as formalin-fixed paraffin-embedded samples. They were analyzed after 3–26 years of storage. DNA was extracted from 114 samples and WGS was run on 85 samples. DNA extraction yielded 313 ng (IQR 96–601) for all samples. A coverage of 11.3x (IQR 9.0–15.9) was recorded for all WGS samples. Three samples stored for > 25 years yielded a coverage of > 25x. Data were generated for 1.7 billion reads per sample (IQR 1.4–2.7). A Transition/Transversion (TiTv) ratio of 2.09 ± 0.05 was calculated for all WGS samples. No associations were found among storage time, DNA yield, or sequencing quality metrics. Conclusions The present study demonstrated the feasibility of whole-genome sequencing based on endomyocardial biopsies. This process could enable large-scale retrospective genomic studies using stored histopathological samples.
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| 5. |
- Landenhed Smith, Maya
(författare)
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Lund Concept for De-airing of the Left Heart. Clinical Evaluation.
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Residual air accumulated air in the pulmonary veins constitutes a challenge to achievment of complete de-airing in open left heart surgery. To adress this problem, a conceptual method for de-airing was developed in Lund comprising bilateral opening of the pleurae to induce pulmonary collapse and a strategy with gradual pulmonary reperfusion and ventilation at weaning from cardiopulmonary bypass (CPB). Aim: To evaluate effectiveness and safety aspects of the Lund concept for de-airing. Methods and results: In the first paper a randomized controlled study was conducted comparing the Lund method to a standardized carbon dioxide (CO2) insufflation technique in twenty patients undergoing open left heart surgery. The number of cerebral microembolic signals (MES) was monitored by transcranial Doppler sonography (TCD) during de-airing and in the first ten minutes after CPB. Residual intracardiac air during the first ten minutes after CPB was graded by transesophageal echocardiography (TEE). The frequency of reopenings of the left ventricular (LV) vent during the first ten minutes after CPB was registered as well as the duration of the de-airing procedure. Compared to the CO2 insufflation technique, the Lund method resulted in fewer MES during de-airing (p<0.001) and in the first ten minutes after CPB (p<0.001), lower grades of intracardiac air during the first three minutes after CPB (p<0.01) and shorter de-airing time, 9 vs 15 minutes, (p=0.001). In the second paper, systemic side-effects of CO2 insufflation were studied in the same twenty patients. Patients in the CO2 insufflation group developed hypercapnia (PaCO2>6 kPa) despite compensational higher gas flows in the oxygenator at 30 minutes of CPB (p<0.001) and acidosis (pH<7.35) already at 15 min of CPB, (p<0.01). CO2 production (VCO2 mL/min) increased during CPB as did the respiratory quotient (RQ; p<0.001) secondary to the extraneously supplied CO2. The mean blood flow velocities in both MCAs increased secondary to increasing PaCO2 (p<0.001 at 45 and 60 minutes of CPB). rSo2 measured by near-infrared spectroscopy (NIRS) were also found higher at 30, 45 and 60 minutes of CPB (p<0.05, p<0.01 and p<0.01, respectively). Scanning electron microscope imaging the cardiotomy suction and LV vent line tubing showed a higher fraction of morphologically changed red blood cells in the CO2 insufflation group. In the third paper we aimed to study the contribution of each component constituting the Lund concept. In a randomized controlled study of twenty patients undergoing open left heart surgery, we compared a group with open pleurae and conventional pulmonary reperfusion and ventilation to a group with intact pleurae combined with staged pulmonary reperfusion and ventilation. During de-airing and in the first ten minutes after CPB, there was a lower number of MES in the group with open pleurae (p<0.05, p<0.01, respectively). A lower amount of residual intracardiac air was also registered in the group with open pleurae in up to six minutes after CPB (p<0.01). The LV vent was reopened fewer times in the group with open pleurae (p<0.001). De-airing time was also shorter in the group with open pleurae, 9 vs 14 minutes (p<0.05). In the fourth paper we studied the impact of single right pulmonary collapse on effectiveness of the Lund method and the effectiveness of a right superior pulmonary vein vent (RSPV). Twenty patients in two prospective cohorts with right pleura open and RSPV respectively, were compared to a historical control cohort from the first paper with bilateral open pleurae and left ventricular apical vent (LVAV). We found a higher number of MES after CPB in the group with single right pulmonary collapse and in the group with RSPV compared to bilateral pulmonary collapse and LVAV (p<0.001, p<0.01, respectively) but no differences in residual intracardiac air graded by TEE or in de-airing times. Conclusion: The Lund concept for de-airing was demonstrated to be an effective and safe alternative to the CO2 insufflation technique. The effectiveness of the Lund method depends primarily on bilateral pulmonary collapse and it may preferably be combined with a left ventricular apical vent.
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| 6. |
- Landenhed Smith, Maya, et al.
(författare)
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Pulmonary collapse alone provides effective de-airing in cardiac surgery: a prospective randomized study.
- 2016
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Ingår i: Perfusion. - : SAGE Publications. - 1477-111X .- 0267-6591. ; 31:4, s. 320-326
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Tidskriftsartikel (refereegranskat)abstract
- We previously described and showed that the method for cardiac de-airing involving: (1) bilateral, induced pulmonary collapse by opening both pleurae and disconnecting the ventilator before cardioplegic arrest and (2) gradual pulmonary perfusion and ventilation after cardioplegic arrest is superior to conventional de-airing methods, including carbon dioxide insufflation of the open mediastinum. This study investigated whether one or both components of this method are responsible for the effective de-airing of the heart.
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| 7. |
- Sonesson, Björn, et al.
(författare)
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Anatomic feasibility of endovascular reconstruction in aortic arch aneurysms.
- 2015
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Ingår i: Vascular. - : SAGE Publications. - 1708-539X .- 1708-5381. ; 23:1, s. 17-20
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Tidskriftsartikel (refereegranskat)abstract
- The purpose was to estimate the proportion of current open aortic arch reconstructions that might be feasible for endovascular repair. From all elective repair made in Southern Sweden in one center between 2005 and 2012, 129 open and eight endovascular aortic arch repairs were identified. The anatomy of the ascending arch and descending aorta as well as the arch vessels was categorized from multiplanar and axial computed tomography scans. Of 129 open cases, only two (1.5%) were suitable for endovascular repair. Among 137 all arch open and endovascular arch reconstructions performed during the study period, only 10 (7%) were candidates for endovascular repair. The most common exclusion for endovascular repair was an excessively large ascending aortic diameter. In conclusion, only a small proportion of patients having an open arch repair are suitable for endovascular arch repair, a finding related to the large diameter of the ascending aorta.
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