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1.
JAMA Netw Open ; 7(4): e247525, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38639933

ABSTRACT

Importance: Aggregated data and long-term follow-up in national health data registers offer the opportunity to compare the performance of mechanical aortic prostheses within the same population. Objective: To investigate the clinical performance of mechanical aortic valve prostheses. Design, Setting, and Participants: This nationwide cohort study included all 5224 patients who underwent primary mechanical aortic valve replacement in Sweden between January 1, 2003, and December 31, 2018. Statistical analysis was performed between May and September 2023. Exposures: Surgical aortic valve replacement with the On-X, Carbomedics, Bicarbon, Standard, Regent, Open Pivot, Masters, or Advantage valve models. Main Outcomes and Measures: The primary outcome was all-cause mortality, and secondary outcomes were reintervention, heart failure, major bleeding, stroke, and embolic events. Regression standardization was used to account for baseline differences. Results: Overall, 5224 patients (mean [SD] age, 56.8 [11.7] years; 3908 men [74.8%]) were included. Total follow-up time was 43 982 person-years (mean [SD], 8.4 [4.6] years; maximum, 17.2 years). After regression standardization, there was a significant difference in 10-year mortality between the Carbomedics model group (17%; 95% CI, 15%-18%), Regent model group (17%; 95% CI, 13%-20%), and Standard model group (17%; 95% CI, 14%-19%) compared with the Bicarbon model group (27%; 95% CI, 21%-34%). Conclusions and Relevance: In this cohort study of mechanical valve surgical aortic replacement outcomes in Sweden, the rate of all-cause mortality was higher in the Bicarbon group than in the Carbomedics, Regent, and Standard model groups. These findings warrant further research on the long-term clinical performance of the Bicarbon valve.


Subject(s)
Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Male , Humans , Middle Aged , Aortic Valve/surgery , Cohort Studies , Prosthesis Design
2.
BJA Open ; 10: 100279, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38680128

ABSTRACT

Background: We hypothesised that a continuous 72-h bilateral parasternal infusion of lidocaine at 2×35 mg h-1 would decrease pain and the inflammatory response after sternotomy for open heart surgery, subsequently improving quality of recovery. Methods: We randomly allocated 45 participants to a 72-h bilateral parasternal infusion of lidocaine or saline commencing after wound closure. The primary outcome was the cumulative patient-controlled analgesia (PCA) morphine consumption at 72 h. Secondary outcomes included total morphine requirement, pain, peak expiratory flow, and serum interleukin-6 concentration. In addition, we used an eHealth platform for a 3-month follow-up of pain, analgesic use, and Quality of Recovery-15 scores. Results: The 72-h PCA morphine requirement was significantly lower in the lidocaine than the saline group (10 mg [inter-quartile range: 5-19 mg] and 28.2 mg [inter-quartile range: 16-42.5 mg], respectively; P=0.014). The total morphine requirement (including morphine administered before the start of PCA) was significantly lower at 24, 48, and 72 h. Pain was well controlled with no difference in pain scores between treatment groups. The peak expiratory flow was lower in the lidocaine group at 72 h. Interleukin-6 concentrations showed no difference at 24, 48, or 72 h. Quality of Recovery-15 scores did not differ between treatment groups at any time during the 3-month follow-up. Conclusions: After sternotomy for open heart surgery, a 72-h bilateral parasternal lidocaine infusion significantly decreased PCA and total morphine requirement. However, neither signs of decreased inflammatory response nor an improvement in recovery was seen. Clinical trial registration: EudraCT number 2018-004672-35.

3.
BMJ Open ; 14(3): e067977, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38508639

ABSTRACT

OBJECTIVES: The objective of this study was to develop clinical classifiers aiming to identify prevalent ascending aortic dilatation in patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). DESIGN AND SETTING: A prospective, single-centre and observational cohort. PARTICIPANTS: The study involved 543 BAV and 491 TAV patients with aortic valve disease and/or ascending aortic dilatation, excluding those with coronary artery disease, undergoing cardiothoracic surgery at the Karolinska University Hospital (Sweden). MAIN OUTCOME MEASURES: Predictors of high risk of ascending aortic dilatation (defined as ascending aorta with a diameter above 40 mm) were identified through the application of machine learning algorithms and classic logistic regression models. EXPOSURES: Comprehensive multidimensional data, including valve morphology, clinical information, family history of cardiovascular diseases, prevalent diseases, demographic details, lifestyle factors, and medication. RESULTS: BAV patients, with an average age of 60.4±12.4 years, showed a higher frequency of aortic dilatation (45.3%) compared with TAV patients, who had an average age of 70.4±9.1 years (28.9% dilatation, p <0.001). Aneurysm prediction models for TAV patients exhibited mean area under the receiver-operating-characteristic curve (AUC) values above 0.8, with the absence of aortic stenosis being the primary predictor, followed by diabetes and high-sensitivity C reactive protein. Conversely, prediction models for BAV patients resulted in AUC values between 0.5 and 0.55, indicating low usefulness for predicting aortic dilatation. Classification results remained consistent across all machine learning algorithms and classic logistic regression models. CONCLUSION AND RECOMMENDATION: Cardiovascular risk profiles appear to be more predictive of aortopathy in TAV patients than in patients with BAV. This adds evidence to the fact that BAV-associated and TAV-associated aortopathy involves different pathways to aneurysm formation and highlights the need for specific aneurysm preventions in these patients. Further, our results highlight that machine learning approaches do not outperform classical prediction methods in addressing complex interactions and non-linear relations between variables.


Subject(s)
Aneurysm , Aortic Diseases , Bicuspid Aortic Valve Disease , Heart Valve Diseases , Humans , Middle Aged , Aged , Aortic Valve/surgery , Heart Valve Diseases/complications , Heart Valve Diseases/surgery , Prospective Studies , Dilatation , Aortic Diseases/complications
4.
Scand Cardiovasc J ; 58(1): 2330345, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38533578

ABSTRACT

Objectives. This study describes growth, local and remote aortic events, and survival in patients with proximal (root, ascending) aortic diameters just below threshold for operation. Methods. Patients with proximal aortic diameter of 4.5 to 5.4 cm at baseline, were followed with serial computed tomography studies and data collected retrospectively. Aortic growth rate was estimated using mixed effects modelling. Clinical and radiological features associated with outcomes (all-cause death, aortic death, local or remote aortic events (dissection, rupture, intramural hematoma, or intervention)) were assessed with Cox analysis. Survival and freedom from events were estimated using Kaplan-Meier methods. Results. 80 patients underwent 274 CT scans during 265 patient-years. Median proximal aortic growth was 0.2 cm in 3 years. 32 events occurred in 28 patients (35%). Eleven events were local, all elective proximal aortic surgery. Nine events were remote: 5 type B aortic dissections, 3 descending aneurysms undergoing elective repair, and one infrarenal aortic rupture. Twelve patients died, half of type B aortic dissection. Relative survival compared to a matched normal population was 82% (95% confidence limits 55-98%) at 10 years. In Cox analysis, increased descending aortic diameter was an independent predictor of all-cause death (hazard ratio [HR], 1.39) and aortic death (HR 1.96). Conclusions. Descending, but not proximal, aortic growth was predictive of lethal events. The decreased relative survival, the substantial number of remote aortic events and aortic deaths strongly suggest continuous serial CT surveillance of the entire aorta. Other indicators than proximal aortic diameter appear needed to improve management of this patient group.


Subject(s)
Aortic Aneurysm, Thoracic , Aortic Dissection , Humans , Aorta, Thoracic/surgery , Retrospective Studies , Tomography, X-Ray Computed/methods , Risk Factors
5.
medRxiv ; 2024 Feb 04.
Article in English | MEDLINE | ID: mdl-38352379

ABSTRACT

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver pathology in western countries, with serious public health consequences. Efforts to identify causal genes for NAFLD have been hampered by the relative paucity of human data from gold-standard magnetic resonance quantification of hepatic fat. To overcome insufficient sample size, genome-wide association studies using NAFLD surrogate phenotypes have been used, but only a small number of loci have been identified to date. In this study, we combined GWAS of NAFLD composite surrogate phenotypes with genetic colocalization studies followed by functional in vitro screens to identify bona fide causal genes for NAFLD. Approach & Results: We used the UK Biobank to explore the associations of our novel NAFLD score, and genetic colocalization to prioritize putative causal genes for in vitro validation. We created a functional genomic framework to study NAFLD genes in vitro using CRISPRi. Our data identify VKORC1, TNKS, LYPLAL1 and GPAM as regulators of lipid accumulation in hepatocytes and suggest the involvement of VKORC1 in the lipid storage related to the development of NAFLD. Conclusions: Complementary genetic and genomic approaches are useful for the identification of NAFLD genes. Our data supports VKORC1 as a bona fide NAFLD gene. We have established a functional genomic framework to study at scale putative novel NAFLD genes from human genetic association studies.

6.
J Mol Med (Berl) ; 101(10): 1323-1333, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37698712

ABSTRACT

Degenerative ascending aortic aneurysm (AscAA) is a silent and potentially fatal disease characterized by excessive vascular inflammation and fibrosis. We aimed to characterize the cellular and molecular signature for the fibrotic type of endothelial mesenchymal transition (EndMT) that has previously been described in degenerative AscAA. Patients undergoing elective open-heart surgery for AscAA and/or aortic valve repair were recruited. Gene expression in the intima-media of the ascending aorta was measured in 22 patients with non-dilated and 24 with dilated aortas, and candidate genes were identified. Protein expression was assessed using immunohistochemistry. Interacting distal gene enhancer regions were identified using targeted chromosome conformation capture (HiCap) in untreated and LPS-treated THP1 cells, and the associated transcription factors were analyzed. Differential expression analysis identified SPP1 (osteopontin) as a key gene in the signature of fibrotic EndMT in patients with degenerative AscAA. The aortic intima-media expression of SPP1 correlated with the expression of inflammatory markers, the level of macrophage infiltration, and the aortic diameter. HiCap analysis, followed by transcription factor binding analysis, identified ETS1 as a potential regulator of SPP1 expression under inflammatory conditions. In conclusion, the present findings suggest that SPP1 may be involved in the development of the degenerative type of AscAA. KEY MESSAGES: In the original manuscript titled "SPP1/osteopontin, a driver of fibrosis and inflammation in degenerative ascending aortic aneurysm?" by David Freiholtz, Otto Bergman, Saliendra Pradhananga, Karin Lång, Flore-Anne Poujade, Carl Granath, Christian Olsson, Anders Franco-Cereceda, Pelin Sahlén, Per Eriksson, and Hanna M Björck, we present novel findings on regulatory factors on osteopontin (SPP1) expression in immune cells involved in degenerative ascending aortic aneurysms (AscAA). The central findings convey: SPP1 is a potential driver of the fibrotic endothelial-to-mesenchymal transition in AscAA. SPP1/osteopontin expression in AscAA is predominately by immune cells. ETS1 is a regulatory transcription factor of SPP1 expression in AscAA immune cells.

7.
Aorta (Stamford) ; 11(3): 97-106, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37619566

ABSTRACT

BACKGROUND: This study aimed to assess predictors of a composite endpoint (reoperation for aortic valve [AV] failure or aortic regurgitation [AR] grade ≥ 2) after reimplantation of the aortic valve (RAV) using the Valsalva graft. METHODS: From 2012 to 2021, 112 patients underwent RAV in a single center. Clinical and echocardiographic data were collected retrospectively. Cox regression analysis was used to identify predictors of the composite endpoint. Kaplan-Meier methods were used for time-to-event analysis. RESULTS: Median (interquartile range) age was 52 years (44, 62). Nineteen patients (17%) were operated for acute Type A aortic dissection, and the remainder for aortic root aneurysm, 60 mm or larger in 12/112 (11%). Thirty-day mortality was 1/112 (1%). During follow-up, four patients (3.6%) were reoperated for AV failure, and another nine patients (8.1%) developed AR grade ≥ 2. Overall estimated freedom from reoperation or AR grade ≥ 2 was 87% (95% confidence interval: 76-93%) at 5 years. Significantly lower estimated 5-year freedom from the composite endpoint was found in cases with simultaneous aortic valve repair (AVr; 77 vs. 90%, p = 0.007) and nearly significant for large (≥ 6 cm) aortic root diameter (82 vs. 87%, p = 0.055). In Cox's analysis, aortic root diameter and simultaneous AVr were independent predictors for the composite endpoint. CONCLUSION: Outcomes (survival, reoperation, freedom from AR grade ≥ 2) with RAV were good up to 11-year follow-up. Larger aortic root diameter and simultaneous AVr were identified as predictors for reoperation or AR grade ≥ 2. Long-term follow-up remains necessary to confirm adequate AV function.

9.
Acta Anaesthesiol Scand ; 67(9): 1256-1265, 2023 10.
Article in English | MEDLINE | ID: mdl-37344999

ABSTRACT

BACKGROUND: Peripheral blocks are increasingly used for analgesia after video-assisted thoracic surgery (VATS). We hypothesised that addition of sufentanil and adrenaline to levobupivacaine would improve the analgesic effect of a continuous extrapleural block. METHODS: We randomised 60 patients undergoing VATS to a 5-mL h-1 extrapleural infusion of levobupivacaine at 2.7 mg mL-1 (LB group) or levobupivacaine at 1.25 mg mL-1 , sufentanil at 0.5 µg mL-1 , and adrenaline at 2 µg mL-1 (LBSA group). The primary outcome was the cumulative morphine dose administered as patient-controlled analgesia (PCA-morphine) at 48 and 72 h. The secondary outcomes were pain according to numerical rating scale (NRS) at rest and after two deep breaths twice daily, peak expiratory flow (PEF) daily, quality of recovery (QoR)-15 score at 1 day and 3 weeks postoperatively, serum levobupivacaine concentrations at 1 h after the start and at the end of the intervention, and adverse events. RESULTS: At 48 h, the median cumulative PCA-morphine dose for the LB group was 6 mg (IQR, 2-10 mg) and for the LBSA group 7 mg (IQR, 3-13.5 mg; p = .378). At 72 h, morphine doses were 10 mg (IQR, 3-22 mg) and 12.5 mg (IQR, 4-21 mg; p = .738), respectively. Median NRS score at rest and after two deep breaths was 3 or lower at all time points for both treatment groups. PEF did not differ between groups. Three weeks postoperatively, only the LB group returned to baseline QoR-15 score. The LB group had higher, but well below toxic, levobupivacaine concentrations at 48 and 72 h. The incidence of nausea, dizziness, pruritus and headache was equally low overall. CONCLUSION: For a continuous extrapleural block, and compared to plain levobupivacaine at 13.5 mg h-1 , levobupivacaine at 6.25 mg h-1 with addition of sufentanil and adrenaline did not decrease postoperative morphine consumption. The levobupivacaine serum concentrations after 48 and 72 h of infusion were well below toxic levels, therefore our findings support the use of the maximally recommended dose of levobupivacaine for a 2- to 3-day continuous extrapleural block.


Subject(s)
Sufentanil , Thoracic Surgery, Video-Assisted , Humans , Analgesia, Patient-Controlled , Analgesics, Opioid/therapeutic use , Epinephrine , Levobupivacaine/therapeutic use , Morphine/therapeutic use , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Thoracic Surgery, Video-Assisted/adverse effects
11.
Scand Cardiovasc J ; 57(1): 2210275, 2023 12.
Article in English | MEDLINE | ID: mdl-37209043

ABSTRACT

Background. It remains equivocal if acute type A aortic dissection (ATAAD) surgical outcomes are improving. We analyzed current outcome trends to evaluate improvements and to identify predicting variables. Methods. From 2015 to 2020, 204 patients underwent surgery for ATAAD and were divided into recent (n = 102) and earlier (n = 102) groups. Uni- and multivariable statistical analysis was performed to identify predictors of 30-day mortality. Results. Thirty-day mortality decreased significantly in the recent group (3.9% vs 14.6%, p = .014). Prevalence of neurological insult also decreased significantly (13% vs 25%, p = .028). Other major complications remained unchanged. There was no statistically significant difference in overall 30-day mortality between low-volume vs high-volume surgeons (12.3% vs 7.3%, p = .21). The number of surgeons performing ATAAD procedures decreased from nine in 2015 to five in 2020. Preoperative lactate (OR 1.24, 95%CI 1.03-1.51), dissection of any arch vessel (OR 14.2, 95%CI 1.79-113), non-normal left ventricular ejection fraction (OR 12.5, 95%CI 2.54-61.6), biological composite graft (OR 19.1, 95%CI 2.75-133), concomitant coronary artery bypass grafting (OR 38.8, 95%CI 2.91-517) and intraoperative adverse event (OR 9.5, 95%CI 2.22-40.9) were statistically significant independent predictors of mortality. Conclusions. Early outcomes after ATAAD improved in the most recent experience. Part of the explanation may be fewer surgeons performing more procedures annually, a relatively conservative approach to the extent of aortic resection and ensuring adequate cerebral protection. Major complications remain prevalent and require attention to be further reduced.


Subject(s)
Aortic Aneurysm, Thoracic , Aortic Dissection , Humans , Stroke Volume , Treatment Outcome , Retrospective Studies , Ventricular Function, Left , Aortic Dissection/diagnostic imaging , Aortic Dissection/surgery , Acute Disease
12.
J Mol Med (Berl) ; 101(7): 801-811, 2023 07.
Article in English | MEDLINE | ID: mdl-37162557

ABSTRACT

Bicuspid aortic valve (BAV) is the most common congenital heart malformation frequently associated with ascending aortic aneurysm (AscAA). Epithelial to mesenchymal transition (EMT) may play a role in BAV-associated AscAA. The aim of the study was to investigate the type of EMT associated with BAV aortopathy using patients with a tricuspid aortic valve (TAV) as a reference. The state of the endothelium was further evaluated. Aortic biopsies were taken from patients undergoing open-heart surgery. Aortic intima/media miRNA and gene expression was analyzed using Affymetrix human transcriptomic array. Histological staining assessed structure, localization, and protein expression. Migration/proliferation was assessed using ORIS migration assay. We show different EMT types associated with BAV and TAV AscAA. Specifically, in BAV-associated aortopathy, EMT genes related to endocardial cushion formation were enriched. Further, BAV vascular smooth muscle cells were less proliferative and migratory. In contrast, TAV aneurysmal aortas displayed a fibrotic EMT phenotype with medial degenerative insults. Further, non-dilated BAV aortas showed a lower miRNA-200c-associated endothelial basement membrane LAMC1 expression and lower CD31 expression, accompanied by increased endothelial permeability indicated by increased albumin infiltration. Embryonic EMT is a characteristic of BAV aortopathy, associated with endothelial instability and vascular permeability of the non-dilated aortic wall. KEY MESSAGES: Embryonic EMT is a feature of BAV-associated aortopathy. Endothelial integrity is compromised in BAV aortas prior to dilatation. Non-dilated BAV ascending aortas are more permeable than aortas of tricuspid aortic valve patients.


Subject(s)
Bicuspid Aortic Valve Disease , Heart Valve Diseases , MicroRNAs , Humans , Bicuspid Aortic Valve Disease/complications , Bicuspid Aortic Valve Disease/metabolism , Bicuspid Aortic Valve Disease/pathology , Heart Valve Diseases/genetics , Heart Valve Diseases/complications , Heart Valve Diseases/metabolism , Epithelial-Mesenchymal Transition/genetics , Aortic Valve/metabolism , MicroRNAs/metabolism , Endothelium/metabolism , Endothelium/pathology
13.
Vasc Health Risk Manag ; 19: 325-328, 2023.
Article in English | MEDLINE | ID: mdl-37251602

ABSTRACT

Background: Cardio-ankle vascular index (CAV) is a measure of systemic arterial stiffness and has been shown to increase after aortic valve surgery. However, change in CAVI-derived pulse wave morphology has not previously been addressed. Case Study: A 72-year-old female was transferred to a large center for heart valve interventions for evaluation of her aortic stenosis. Few co-morbidities were detected on medical history, other than previous radiation treatment for breast cancer, and no signs of other concomitant cardiovascular disease. The patient was accepted for surgical aortic valve replacement due to severe aortic valve stenosis and arterial stiffness was assessed with CAVI, as part of an ongoing clinical study. The pre-operative CAVI was 4.7 which after surgery increased almost 100% to 9.35. In tandem, the slope of systolic upstroke pulse morphology captured from brachial cuffs was changed from a prolonged flattened pattern to a steeper. Conclusion: After aortic valve replacement surgery due to aortic valve stenosis, in addition to increased CAVI-derived measures of arterial stiffness, the slope of the CAVI-derived upstroke pulse wave morphology changes to a steeper slope. This finding could have implications in the future of aortic valve stenosis screening and utilization of CAVI.


Subject(s)
Aortic Valve Stenosis , Vascular Stiffness , Female , Humans , Aged , Ankle/blood supply , Pulse Wave Analysis , Cardio Ankle Vascular Index , Ankle Brachial Index , Aortic Valve Stenosis/complications , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery
14.
J Am Coll Cardiol ; 81(10): 964-975, 2023 03 14.
Article in English | MEDLINE | ID: mdl-36889875

ABSTRACT

BACKGROUND: Prosthesis-patient mismatch (PPM) is common following surgical aortic valve replacement (SAVR). OBJECTIVES: The purpose of this study was to quantify the impact of PPM on all-cause mortality, heart failure hospitalization, and reintervention following bioprosthetic SAVR. METHODS: This observational nationwide cohort study from SWEDEHEART (Swedish Web system for Enhancement and Development of Evidence based care in Heart disease Evaluated According to Recommended Therapies) and other national registers included all patients who underwent primary bioprosthetic SAVR in Sweden from 2003 to 2018. PPM was defined according to the Valve Academic Research Consortium 3 criteria. Outcomes were all-cause mortality, heart failure hospitalization, and aortic valve reintervention. Regression standardization was used to account for intergroup differences and to estimate cumulative incidence differences. RESULTS: We included 16,423 patients (no PPM: 7,377 [45%]; moderate PPM: 8,502 [52%]; and severe PPM: 544 [3%]). After regression standardization, the cumulative incidence of all-cause mortality at 10 years was 43% (95% CI: 24%-44%) in the no PPM group compared with 45% (95% CI: 43%-46%) and 48% (95% CI: 44%-51%) in the moderate and severe PPM groups, respectively. The survival difference at 10 years was 4.6% (95% CI: 0.7%-8.5%) and 1.7% (95% CI: 0.1%-3.3%) in no vs severe PPM and no vs moderate PPM, respectively. The difference in heart failure hospitalization at 10 years was 6.0% (95% CI: 2.2%-9.7%) in severe vs no PPM. There was no difference in aortic valve reintervention in patients with or without PPM. CONCLUSIONS: Increasing grades of PPM were associated with long-term mortality, and severe PPM was associated with increased heart failure. Moderate PPM was common, but the clinical significance may be negligible because the absolute risk differences in clinical outcomes were small.


Subject(s)
Aortic Valve Stenosis , Heart Failure , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Transcatheter Aortic Valve Replacement , Humans , Aortic Valve/surgery , Heart Valve Prosthesis Implantation/adverse effects , Cohort Studies , Aortic Valve Stenosis/surgery , Treatment Outcome , Heart Valve Prosthesis/adverse effects , Heart Failure/epidemiology , Heart Failure/surgery , Risk Factors , Prosthesis Design
15.
Rheumatology (Oxford) ; 62(3): 1187-1196, 2023 03 01.
Article in English | MEDLINE | ID: mdl-35961031

ABSTRACT

OBJECTIVES: The antiphospholipid syndrome is defined by antiphospholipid antibodies (aPL) together with arterial and/or venous thromboembolism and/or obstetric morbidities. aPL are overrepresented in SLE and acute myocardial infarction, but it is unknown whether aPL are associated with calcific aortic valve stenosis (CAVS) in the general population. The prevalence of aPL and other SLE-associated autoantibodies and their impact on aortic valve transcriptomics were therefore determined. METHODS: A total of 233 tricuspid CAVS cases (median age 74, 69% male) and an age- and sex-matched control population were included. aPL were measured as anti-cardiolipin and anti-ß2Glycoprotein-I of IgG/M/A isotypes. Resilient, thickened and calcified aortic valve (AV) tissue derived from five aPL positive and five matched aPL negative CAVS patients undergoing surgical aortic valve replacement were analysed by microarrays. RESULTS: The prevalence of positivity for any aPL (IgG/M/A) in patients with CAVS was 6.4% (95% CI 3.6% - 10.4%: n = 233). aPL IgG was significantly more prevalent in CAVS cases vs controls (4.6% vs 0.6%, P = 0.04). AV tissue from aPL IgG/IgM-positive patients was negatively enriched in pathways related to interferon signalling. One hundred differentially expressed genes could predict local AV CAVS progression with supervised machine learning algorithms. CONCLUSIONS: aPL IgG was more common in CAVS patients compared with matched controls and aPL positivity was associated with altered AV transcriptomics related to local disease progression and interferon pathways. Further studies should aim to establish aPL as a possible risk marker and/or causal factor for CAVS and could offer new precision therapeutic targets.


Subject(s)
Antiphospholipid Syndrome , Aortic Valve Stenosis , Lupus Erythematosus, Systemic , Pregnancy , Female , Humans , Male , Aged , Aortic Valve , Antibodies, Antiphospholipid , Aortic Valve Stenosis/etiology , Antiphospholipid Syndrome/complications , Immunoglobulin G , Lupus Erythematosus, Systemic/complications
16.
Aorta (Stamford) ; 10(3): 122-130, 2022 Jun.
Article in English | MEDLINE | ID: mdl-36318933

ABSTRACT

BACKGROUND: Identifying a useful marker for thoracic aortic dilatation (TAD) could help improve informed clinical decisions, enhance diagnosis, and develop TAD screening programs. Inguinal hernia could be such a marker. This study tested the hypothesis that the thoracic aorta is larger and more often dilated in men with previous inguinal hernia repair versus nonhernia controls. METHODS: Four hundred men each with either previous inguinal hernia repair or cholecystectomy (controls) were identified to undergo chest computed tomography to measure the diameter of the thoracic aorta in the aortic root, ascending, isthmic, and descending aorta and to provide self-reported health data. Presence of TAD (root or ascending diameter > 45 mm; isthmic or descending diameter > 35 mm) and thoracic aortic diameters were compared between groups and associations explored using uni- and multivariable statistical methods. RESULTS: Complete data were obtained from 470/718 (65%) eligible participants. TAD prevalence was significantly higher in the inguinal hernia group: 21 (10%) versus 6 (2.4%), p = 0.001 for proximal TAD, 29 (13%) versus 21 (8.3%), p = 0.049 for distal TAD, and 50 (23%) versus 27 (11%), p < 0.001 for all aortic segments combined. In multivariable analysis, previous inguinal hernia repair was independently associated with dilatation of the proximal aorta (odds ratio 5.3, 95% confidence interval 1.8-15, p = 0.003). Contrarily, mean thoracic aortic diameters were similar (root and ascending aorta) or showed clinically irrelevant differences (isthmus and descending aorta). CONCLUSION: TAD, but not increased aortic diameters on average, was common and significantly more prevalent in men with previous inguinal hernia repair. Hernia could be a marker condition associated with increased prevalence of TAD. Ultimately, TAD screening could consider hernia as a possible selection criterion.

17.
J Cardiovasc Surg (Torino) ; 63(6): 700-707, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36106399

ABSTRACT

BACKGROUND: Allogenic blood product usage is associated with worse outcomes in open repair of descending and thoracoabdominal aortic aneurysms. This pilot study evaluated the safety and efficacy of a novel modification of the left heart bypass (LHB) circuit to reduce intraoperative blood transfusions. METHODS: In modified LHB, pump suckers collected shed blood that was directly retransfused through a femoral vein cannula. In standard LHB, cellsavers were used to collect, wash, and retransfuse shed blood. Consecutive patients undergoing elective surgical descending or thoracoabdominal aneurysm repair using modified (N.=12) or standard (N.=21) LHB were compared. Intraoperative blood product use was the primary outcome. Hypotensive episodes, lactate levels, and adverse events (early mortality, spinal cord injury, renal and respiratory insufficiency) were secondary outcomes. RESULTS: Groups were comparable regarding pre- and intraoperative variables. No perfusion-related adverse events occurred. With modified LHB, intraoperative blood product use was significantly reduced: packed red blood cells by 60% from 10 to 4 units (P=0.002), fresh frozen plasma by 70% from 17 to 5 units (P<0.001) as well as retransfused cellsaver volume by 75%, from 4500 mL to 1110 mL (P<0.001). Hemodynamic instability occurred in 1 (8.3%) vs. 6 (29%), P=0.22 and overall lactate levels were significantly reduced (P=0.045) with modified LHB. Adverse events combined occurred in 1/12 vs. (P=0.022). CONCLUSIONS: The novel modified LHB with direct retransfusion was safe and associated with significantly reduced intraoperative blood product use, reduced lactate production and improved clinical outcomes as compared to standard LHB and could represent an important clinical improvement.


Subject(s)
Aortic Aneurysm, Thoracic , Postoperative Complications , Humans , Pilot Projects , Retrospective Studies , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/surgery , Blood Transfusion , Lactates , Treatment Outcome
18.
Scand Cardiovasc J ; 56(1): 352-359, 2022 12.
Article in English | MEDLINE | ID: mdl-36151718

ABSTRACT

OBJECTIVES: Open surgical repair (OSR) of descending and thoracoabdominal aortic aneurysms carries risks of mortality and major complications. Patients with connective tissue disorders (CTD) are younger and require safe, efficient treatment with long-term durability. This study provides current outcome data to help inform treatment decisions. METHODS: All OSRs of descending thoracic aortic aneurysm (DTAA) or thoracoabdominal aortic aneurysm (TAAA) from January 2011 to July 2021 were included in a retrospective cohort study. Primary outcome measures were early and follow-up mortality and reintervention. Secondary outcome measures were major complications. Kaplan-Meier methods were used to estimate reintervention-free survival. RESULTS: A total of 26 OSRs (7 DTAA, 19 TAAA) were performed in 23 patients: 20 (77%) Marfan and 6 (23%) Loeys-Dietz syndrome; median age 43 years. Aortic dissection was present in 100% and 3/26 (12%) were urgent. Early mortality was 1/26 (3.8%). No patient suffered spinal cord ischemia, stroke, vocal cord paralysis, or re-exploration for bleeding. The transient respiratory failure occurred in 19% (5/26) and transient renal replacement therapy in 15% (4/26). Renal function normalized in all patients within 3 months. During follow-up (median 4.6, range 0-11 years) there were no deaths and only one re-intervention on a previously operated aortic segment, resulting in 92% reintervention-free survival at 5 years. CONCLUSIONS: In dedicated units, open surgical DTAA and TAAA repair in patients with CTD can be performed with a very low risk of death, severe complications and, late re-intervention. For CTD patients with reasonable risk, OSR should remain the first line of treatment.


Subject(s)
Aortic Aneurysm, Thoracic , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Adult , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/surgery , Blood Vessel Prosthesis Implantation/adverse effects , Connective Tissue/surgery , Humans , Postoperative Complications , Retrospective Studies , Risk Factors , Treatment Outcome
19.
Ann Cardiothorac Surg ; 11(4): 448-458, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35958533

ABSTRACT

Background: The objective of this study is to investigate clinical outcomes in patients with bicuspid aortic valves (BAV) after surgical treatment for endocarditis. Methods: This was a population-based, observational cohort study, conducted on all patients who received aortic valve surgery for native or prosthetic valve endocarditis at Karolinska University Hospital between 2002-2020. Baseline characteristics and postoperative complications were collected from the institutional surgical database and patient medical charts. The primary endpoint was all-cause mortality. We used unadjusted and adjusted Cox regression to determine the association between valve morphology and long-term mortality. Results: Of the 338 patients, 122 (36%) had a BAV and 216 (64%) had a tricuspid aortic valve (TAV). The mean follow-up was 5.8 years (maximum 18.4 years). Survival rates at one, five, ten and 14 years were 88%, 81%, 78% and 76% versus 85%, 69%, 58% and 43%, in BAV and TAV patients, respectively [adjusted hazard ratio (HR) 0.64; 95% confidence interval (CI): 0.39-1.05]. In patients with native valve endocarditis, those with BAV had lower all-cause mortality compared to those with TAV (adjusted HR 0.44; 95% CI: 0.22-0.89), despite having a higher prevalence of perivalvular abscess (40% versus 22%, respectively, in BAV and TAV patients). In patients with prosthetic valve endocarditis, original valve morphology did not affect all-cause mortality (adjusted HR 1.94; 95% CI: 0.64-5.87). Conclusions: In patients with native valve endocarditis, a BAV was associated with improved survival after surgical treatment. In patients with prosthetic valve endocarditis, survival was not affected by the original valve morphology of the patient.

20.
Trials ; 23(1): 516, 2022 Jun 20.
Article in English | MEDLINE | ID: mdl-35725494

ABSTRACT

BACKGROUND: Multimodal analgesia that provides optimal pain treatment with minimal side effects is important for optimal recovery after open cardiac surgery. Regional anaesthesia can be used to block noxious nerve signals. Because sternotomy causes considerable pain that lasts several days, a continuous nerve block is advantageous. Previous studies on continuous sternal wound infusion or parasternal blocks with long-acting local anaesthetics have shown mixed results. This study aims to determine whether a continuous bilateral parasternal block with lidocaine, which is a short-acting local anaesthetic that has a favourable safety/toxicity profile, results in effective analgesia. We hypothesise that a 72-hour continuous parasternal block with 0.5% lidocaine at a rate of 7 ml/hour on each side provides effective analgesia and reduces opioid requirement. We will evaluate whether recovery is enhanced. METHODS: In a prospective, randomised, double-blinded manner, 45 patients will receive a continuous parasternal block with either 0.5% lidocaine or saline. The primary endpoint is cumulated intravenous morphine by patient-controlled analgesia at 72 hours. Secondary end-points include the following: (1) the cumulated numerical rating scale (NRS) score recorded three times daily at 72 hours; (2) the cumulated NRS score after two deep breaths three times daily at 72 hours; (3) the NRS score at rest and after two deep breaths at 2, 4, 8 and 12 weeks after surgery; (4) oxycodone requirement at 2, 4, 8 and 12 weeks after surgery; (5) Quality of Recovery-15 score preoperatively compared with that at 24, 48 and 72 hours, and at 2, 4, 8 and 12 weeks after surgery; (6) preoperative peak expiratory flow compared with postoperative daily values for 3 days; and (7) serum concentrations of interleukin-6 and lidocaine at 1, 24, 48 and 72 hours postoperatively compared with preoperative values. DISCUSSION: Adequate analgesia is important for quality of care and vital to a rapid recovery after cardiac surgery. This study aims to determine whether a continuous parasternal block with a short-acting local anaesthetic improves analgesia and recovery after open cardiac procedures. TRIAL REGISTRATION: The study was registered in the European Clinical Trials Database on 27/9/2019 (registration number: 2018-004672-35).


Subject(s)
Cardiac Surgical Procedures , Lidocaine , Analgesics, Opioid , Anesthetics, Local , Cardiac Surgical Procedures/adverse effects , Humans , Pain Measurement , Pain, Postoperative/diagnosis , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Prospective Studies , Randomized Controlled Trials as Topic , Sternotomy/adverse effects
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