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- Janiec, Mikael
(author)
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Clinically-driven angiography after coronary artery bypass surgery : Results from the SWEDEHEART registry
- 2019
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Doctoral thesis (other academic/artistic)abstract
- The success of coronary artery bypass grafting (CABG) arguably depends on the patency rate of the conduits. The saphenous vein grafts (SVGs) most often used are subject to graft disease and their reduced long-term patency compared to left internal mammary artery (IMA) grafts is well established. Postoperative coronary artery disease (CAD) symptoms, such as angina or myocardial infarction can undoubtedly be linked to graft failure or progression of atherosclerosis in the native coronary vessels, but the contribution from each of these processes is not completely understood.The aim of this thesis was to use clinically-driven angiography as the main outcome measure in studying different bypass conduits and surgical techniques. This endpoint has a very low risk of misclassification, and is likely to have a high association with recurrence of CAD symptoms. The SWEDEHEART registry provides extensive data on all patients undergoing cardiac surgery in Sweden as well as records of angiographies and coronary interventions.We studied the incidence of postoperative angiography in 46 663 CABG patients operated with IMA and SVGs. Young age, female sex, presence of diabetes, normal left ventricle function, previous PCI, prior MI, emergency surgery and one or two distal anastomoses were associated with a higher risk. We also studied 6 977 CABG operated individuals with three or more grafted vessels that experienced a postoperative angiography and had available records on individual graft patency. Almost one third of catheterized individuals with CAD symptoms did not demonstrate any failed grafts and in 18% of early and 10% of late angiographies the IMA-graft had failed.We compared 862 patients operated with bilateral IMA grafts and 1036 cases of IMA and radial artery grafts with 46 343 cases of IMA and SVGs. When adjusted for risk factors no improvement in outcome could be seen for patients operated with multiple arterial grafts. We also compared 1371 patients operated with “no-touch” SVGs with a propensity-matched cohort of patients with conventional SVGs. An improvement in the risk for angiography could be seen for the “no-touch” group but not for the need of repeat intervention or survival.Postoperative angiography is a useful endpoint in studying long-term outcome after CABG surgery. It is less sensitive than mortality to variations in the baseline covariates and thereby possibly less susceptible to confounding by indication. The causation behind the return of CAD symptoms after CABG surgery and the relative importance of the individual contributions from vein graft failures, failure of the IMA graft, as well as from progression of atherosclerotic plaques in both grafted and non-grafted coronary arteries, remains to be determined.
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| 2. |
- Janiec, Mikael, et al.
(author)
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Graft failure and recurrence of symptoms after coronary artery bypass grafting
- 2018
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In: Scandinavian Cardiovascular Journal. - : TAYLOR & FRANCIS LTD. - 1401-7431 .- 1651-2006. ; 52:3, s. 113-119
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Journal article (peer-reviewed)abstract
- Objectives: Saphenous vein grafts (SVGs) most often used in coronary artery bypass grafting (CABG) are subject to graft disease and have poor long-term patency, however the clinical implication of this is not completely known. We aim to assess the influence of graft failure on the postoperative recurrence of coronary artery disease (CAD) symptoms in relation to the contribution from progression of atherosclerosis in the native coronary vessels.Design: Within the SWEDEHEART registry we identified 46,663 CABG cases between 2001 and 2015 with patient age 40-80 years where single internal mammary artery (IMA) anastomosis (IMA), single IMA with one (1SVG) or multiple SVG anastomoses (2+ SVG) had been performed. Clinical characteristics as well as mortality and postoperative incidence of coronary angiography were recorded and multivariable adjusted hazard ratios were calculated. Indications for the angiographies and occurrence of graft failure were also registered.Results: The adjusted hazard ratio for death was similar for the three groups. The adjusted hazard ratio for being submitted to angiography as compared to 2+ SVG was (95% CI) 1.24 (1.06-1.46) for IMA and 1.21 (1.15-1.28) for 1SVG. Failed grafts were found at the first postoperative angiography with preceding CAD symptoms in 21.4% of patients in the IMA group, 41.6% in the 1SVG group and 61.1% in the 2+ SVG group.Conclusions: A substantial amount of angiographies occur in patients without any graft failure and a large part of postoperative recurrence of CAD symptoms and are likely attributed to IMA failure or progression of atherosclerosis in the native coronary arteries.
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| 3. |
- Janiec, Mikael, et al.
(author)
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Internal thoracic artery graft failure and recurrence of symptoms following single-vessel coronary artery bypass graft surgery
- 2023
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In: Journal of Cardiothoracic Surgery. - : BioMed Central (BMC). - 1749-8090. ; 18
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Journal article (peer-reviewed)abstract
- Objectives: Coronary events and disease recurrence following coronary artery bypass (CABG) surgery could derive from either failure in the internal thoracic artery (ITA) graft, failure in other conduits or progressive disease in the coronaries. We aim to estimate the contribution of ITA graft failure to the recurrence of symptoms after CABG surgery.Methods: Within the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry, we identified patients who had coronary artery bypass grafting from 1997 to 2020 with a single-vessel ITA graft bypass. Deaths, postoperative incidence of coronary angiography and the presence of a failed graft at the time of the angiography were recorded.Results: The study population consisted of 1939 patients with a mean follow-up time (SD) of 17.2 (5.6) years. The cumulative incidence (95% CI) at 20 years for a first clinically-driven postoperative angiography was 38.6% (36.2-41.1). A failed ITA graft was reported in 16.4% of the angiographies.Conclusions: A substantial part of recurrent symptoms of coronary artery disease do not seem to be related to ITA failure. Disease progression in the native coronary vessels may instead be the main driver of symptom recurrence.
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| 4. |
- Janiec, Mikael, et al.
(author)
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Symptomatic late saphenous vein graft failure in coronary artery bypass surgery
- 2023
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In: INTERDISCIPLINARY CARDIOVASCULAR AND THORACIC SURGERY. - : Oxford University Press. - 2753-670X. ; 36:4
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Coronary artery bypass grafting for advanced coronary artery disease is a well-established procedure with excellent long-term results. The issue of saphenous vein graft (SVG) performance and its relation to clinical symptoms and thereby the potential for improvement by using superior grafts are still not fully understood. We aim to estimate the contribution of late SVG failure to the long-term outcome.METHODS: A study population operated between 1997 and 2020, with an internal thoracic artery with a single distal anastomosis and 1, 2 or 3 distal SVG anastomoses, was isolated from the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry. Data regarding postoperative clinically driven coronary angiography and status of bypass grafts were collected.RESULTS: The study population consisted of 44 951 patients. Clinically driven angiography occurred in 10.1% (9.5-10.8), 7.9% (7.6-8.3) and 7.1% (6.7-7.5), respectively, of patients within 3 years and 23.6% (22.6-24.5), 20.0% (19.5-20.6) and 17.5% (16.9-18.2), respectively, of patients within 10 years after surgery. Excluding the first 3 postoperative years, no failed SVGs were found in >75%, 60% and 45%, respectively, of cases when an angiography was performed in the first 10 years after surgery.CONCLUSIONS: The results suggest that the risk of symptomatic graft failure due to vein graft disease during the first 10 years after surgery is in the range of 1-2% for every grafted coronary vessel and provide an estimate for the upper limit of the improvements in results that could be achieved by replacing SVGs with superior grafts.
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| 5. |
- Lindblom, Rickard, 1981-, et al.
(author)
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Complement Receptor 2 is increased in cerebrospinal fluid of multiple sclerosis patients and regulates C3 function
- 2016
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In: Clinical Immunology. - : Elsevier BV. - 1521-6616 .- 1521-7035. ; 166, s. 89-95
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Journal article (peer-reviewed)abstract
- Besides its vital role in immunity, the complement system also contributes to the shaping of the synaptic circuitry of the brain. We recently described that soluble Complement Receptor 2 (sCR2) is part of the nerve injury response in rodents. We here study CR2 in context of multiple sclerosis (MS) and explore the molecular effects of CR2 on 0 activation. Significant increases in sCR2 levels were evident in cerebrospinal fluid (CSF) from both patients with relapsing remitting MS (n = 33; 6.2 ng/mL) and secondary-progressive MS (n = 9; 7.0 ng/mL) as compared to controls (n = 18; 4.1 ng/mL). Furthermore, CSF sCR2 levels correlated significantly both with CSF C3 and C1q as well as to a disease severity measure. In vitro, sCR2 inhibited the cleavage and down regulation of Cab to iC3b, suggesting that it exerts a modulatory role in complement activation downstream of C3. These results propose a novel function for CR2/sCR2 in human neuroinflammatory conditions.
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| 6. |
- Lindblom, Rickard, 1981-, et al.
(author)
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Mechanical Reperfusion Following Prolonged Global Cerebral Ischemia Attenuates Brain Injury
- 2021
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In: Journal of Cardiovascular Translational Research. - : Springer Science and Business Media LLC. - 1937-5387 .- 1937-5395. ; 14:2, s. 338-347
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Journal article (peer-reviewed)abstract
- Previous experiments demonstrated improved outcome following prolonged cerebral ischemia given controlled brain reperfusion using extracorporeal circulation. The current study further investigates this. Young adult pigs were exposed to 30 min of global normothermic cerebral ischemia, achieved through intrathoracic clamping of cerebral arteries, followed by 20 min of isolated mechanical brain reperfusion. Leukocyte-filtered blood was delivered by a roller-pump at fixed pressure and flow. One experimental group additionally had a custom-made buffer solution delivered at 1:8 ratio with the blood. Hemodynamics including intracranial pressure were monitored. Blood gases were from peripheral arteries and the sagittal sinus, and intraparenchymal brain microdialysis was performed. The brains were examined by a neuropathologist. The group with the added buffer showed lower intracranial pressure as well as decreased intraparenchymal glycerol and less signs of excitotoxicity and ischemia, although histology revealed similar degrees of injury. A customized mechanical reperfusion improves multiple parameters after prolonged normothermic global cerebral ischemia. [Figure not available: see fulltext.]
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| 7. |
- Lindblom, Rickard P F, 1981-, et al.
(author)
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Hyperglycemia Alters Expression of Cerebral Metabolic Genes after Cardiac Arrest
- 2018
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In: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057 .- 1532-8511. ; 27:5, s. 1200-1211
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Journal article (peer-reviewed)abstract
- Background: Survivors of cardiac arrest often experience neurologic deficits. To date, treatment options are limited. Associated hyperglycemia is believed to further worsen the neurologic outcome. The aim with this study was to characterize expression pathways induced by hyperglycemia in conjunction with global brain ischemia.Methods: Pigs were randomized to high or normal glucose levels, as regulated by glucose and insulin infusions with target levels of 8.5-10 mM and 4-5.5 mM, respectively. The animals were subjected to 5-minute cardiac arrest followed by 8 minutes of cardiopulmonary resuscitation and direct-current shock to restore spontaneous circulation. Global expression profiling of the cortex using microarrays was performed in both groups.Results: A total of 102 genes differed in expression at P<.001 between the hyperglycemic and the normoglycemic pigs. Several of the most strongly differentially regulated genes were involved in transport and metabolism of glucose. Functional clustering using bioinformatics tools revealed enrichment of multiple biological processes, including membrane processes, ion transport, and glycoproteins.Conclusions: Hyperglycemia during cardiac arrest leads to differential early gene expression compared with normoglycemia. The functional relevance of these expressional changes cannot be deduced from the current study; however, the identified candidates have been linked to neuroprotective mechanisms and constitute interesting targets for further studies.
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| 8. |
- Lindblom, Rickard P F, 1981-, et al.
(author)
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Protein Profiling in Serum and Cerebrospinal Fluid Following Complex Surgery on the Thoracic Aorta Identifies Biological Markers of Neurologic Injury.
- 2018
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In: Journal of Cardiovascular Translational Research. - : Springer Science and Business Media LLC. - 1937-5387 .- 1937-5395. ; 11:6, s. 503-516
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Journal article (peer-reviewed)abstract
- Surgery on the arch or descending aorta is associated with significant risk of neurological complications. As a consequence of intubation and sedation, early neurologic injury may remain unnoticed. Biomarkers to aid in the initial diagnostics could prove of great value as immediate intervention is critical. Twenty-three patients operated in the thoracic aorta with significant risk of perioperative neurological injury were included. Cerebrospinal fluid (CSF) and serum were obtained preoperatively and in the first and second postoperative days and assessed with a panel of 92 neurological-related proteins. Three patients suffered spinal cord injury (SCI), eight delirium, and nine hallucinations. There were markers in both serum and CSF that differed between the affected and non-affected patients (SCI; IL6, GFAP, CSPG4, delirium; TR4, EZH2, hallucinations; NF1). The study identifies markers in serum and CSF that reflect the occurrence of neurologic insults following aortic surgery, which may aid in the care of these patients.
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| 9. |
- Lundström, Yasmin, et al.
(author)
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Detection of Changes in Immunohistochemical Stains Caused by Postmortem Delay and Fixation Time
- 2019
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In: Applied immunohistochemistry & molecular morphology (Print). - 1541-2016 .- 1533-4058. ; 27:3, s. 238-245
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Journal article (peer-reviewed)abstract
- In this study, we have systematically assessed the influence of postmortem delay (PMD) and fixation time (FT) on the immunohistochemical (IHC) staining outcome. The IHC method is frequently applied on surgical and postmortem samples in diagnostics and research. To replicate the routine situation, brain tissues from pigs were exposed to either storage in a refrigerator (+8°C), that is, PMD (1 to 168 h), or fixed in 10% buffered formalin, that is, FT (18 to 94 d). Subsequently, the tissue was routinely processed into paraffin blocks to enable construction of tissue microarrays (TMA). Sections cut from the TMA blocks were stained applying 13 different antibodies directed against neuronal and glial antigens. Immunoreactivity applying 5 antibodies was influenced by prolonged PMD and applying 2 antibodies by prolonged FT. None of the staining outcomes related to the PMD or FT were predictable. Loss of TMA cores during processing was primarily influenced by pretreatment and by tissue characteristics (gray/white matter). The test model described here confirmed that these 2 variables, PMD and FT, indeed influence the IHC outcome. The PMD and FT are particularly of importance while assessing tissue samples obtained at autopsy. The result above is also of importance while comparing the IHC outcomes seen in the postmortem setting (various PMD/FT) with surgical samples or with IHC outcome seen in experimental animal setting (controlled PMD/FT). Thus, we suggest that the test model described here is considered when assessing the reliability of the IHC outcome when analyzing tissues with various characteristics.
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| 10. |
- Schagerholm Dahl, Therese, et al.
(author)
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Intermediate outcomes following arch reconstruction with frozen elephant trunk, a single centre study
- 2023
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In: Journal of Cardiothoracic Surgery. - : BioMed Central (BMC). - 1749-8090. ; 18
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Journal article (peer-reviewed)abstract
- Background: Surgery on the aortic arch and proximal descending thoracic aorta can be lifesaving but is also associated with significant morbidity, ranging from minor infections to severe neurological impairments as well as a substantial risk of mortality. The aim of this study is to clinically assess outcomes, with special regards to neurologic injury, as well as to seek to identify predictors of in-hospital mortality in two patient groups with different underlying aortic pathology, aneurysms and dissections, undergoing arch/descending aortic repair.Methods: 34 patients (17 aneurysms, 17 dissections) underwent surgery involving the arch and/or descending aorta, using the Thoraflex or E-Vita frozen elephant trunk graft. 40% were female. Subgroup analysis of aneurysms compared to dissections were performed. Mean follow-up time was 53.9 months and mean age 63.5 years.Results: In-hospital mortality was 18%. Survival was comparable between aneurysms and dissections. Incidence of spinal cord injury was 9% and stroke 9%. 67% suffered any form of neurological affection, when also cognitive afflictions were included. Perioperative reoperation rate was 29% (bleeding 21%, visceral ischemia 6%, infection 2%), the need for postoperative dialysis was 11% and a series of other minor complications such as atrial fibrillation and pleurocentesis were common.Conclusion: Postoperative dialysis was found to be a predictor of in-hospital mortality, while both dialysis as well as reoperation due to bleeding and/or visceral ischemia increased the risk for overall mortality, irrespective of preoperative diagnosis. Previous or current smoking appeared to be associated with negative outcomes regarding both in-hospital and overall mortality during follow-up.Trial registration Retrospectively enrolled.
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