The effect of continuous bilateral parasternal block with lidocaine on patient-controlled analgesia opioid requirement and recovery after open heart surgery: a double-blind randomised controlled trial.

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.

Predictive machine learning models for ascending aortic dilatation in patients with bicuspid and tricuspid aortic valves undergoing cardiothoracic surgery: a prospective, single-centre and observational study.

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.

Aortic events and relative survival in patients with moderately dilated proximal thoracic aorta.

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.

SPP1/osteopontin: a driver of fibrosis and inflammation in degenerative ascending aortic aneurysm?

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.

Extrapleural infusion of levobupivacaine versus levobupivacaine-sufentanil-adrenaline after video-assisted thoracoscopic surgery (VATS): A randomised controlled trial.

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.

Improving outcomes of surgery for acute type A aortic dissection.

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.

Bicuspid aortic valve aortopathy is characterized by embryonic epithelial to mesenchymal transition and endothelial instability.

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.

Pulse Wave Morphology Changes in Aortic Valve Stenosis Detected with Cardio-Ankle Vascular Index.

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.

Effect of Prosthesis-Patient Mismatch on Long-Term Clinical Outcomes After Bioprosthetic Aortic Valve Replacement.

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.

Novel method for direct retransfusion reduces blood transfusions in descending and thoracoabdominal aneurysm repair.

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.

Surgery for endocarditis in patients with bicuspid aortic valves.

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.

Parasternal After Cardiac Surgery (PACS): a prospective, randomised, double-blinded, placebo-controlled trial study protocol for evaluating a continuous bilateral parasternal block with lidocaine after open cardiac surgery through sternotomy.

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).

The tyrosine kinase inhibitor nilotinib targets the discoidin domain receptor DDR2 in calcific aortic valve stenosis.

BACKGROUND AND PURPOSE: Tyrosine kinase inhibitors (TKI) used to treat chronic myeloid leukaemia (CML) have been associated with cardiovascular side effects, including reports of calcific aortic valve stenosis. The aim of this study was to establish the effects of first and second generation TKIs in aortic valve stenosis and to determine the associated molecular mechanisms. EXPERIMENTAL APPROACH: Hyperlipidemic APOE*3Leiden.CETP transgenic mice were treated with nilotinib, imatinib or vehicle. Human valvular interstitial cells (VICs) were isolated and studied in vitro. Gene expression analysis was perfromed in aortic valves from 64 patients undergoing aortic valve replacement surgery. KEY RESULTS: Nilotinib increased murine aortic valve thickness. Nilotinib, but not imatinib, promoted calcification and osteogenic activation and decreased autophagy in human VICs. Differential tyrosine kinase expression was detected between healthy and calcified valve tissue. Transcriptomic target identification revealed that the discoidin domain receptor DDR2, which is preferentially inhibited by nilotinib, was predominantly expressed in human aortic valves but markedly downregulated in calcified valve tissue. Nilotinib and selective DDR2 targeting in VICs induced a similar osteogenic activation, which was blunted by increasing the DDR2 ligand, collagen. CONCLUSIONS AND IMPLICATIONS: These findings suggest that inhibition of DDR2 by nilotinib promoted aortic valve thickening and VIC calcification, with possible translational implications for cardiovascular surveillance and possible personalized medicine in CML patients.

Acetylsalicylic Acid Is Associated With a Lower Prevalence of Ascending Aortic Aneurysm and a Decreased Aortic Expression of Cyclooxygenase 2.

Background Acetylsalicylic acid (ASA) therapy has been associated with a reduced prevalence and growth rate of abdominal as well as intracranial aneurysms, but the relationship between ASA and ascending aortic aneurysm formation remains largely unknown. The aim of the present study was to investigate whether ASA therapy is associated with a lower prevalence of ascending aortic aneurysm in a surgical cohort. Methods and Results One thousand seven hundred patients undergoing open-heart surgery for ascending aortic aneurysm and/or aortic valve disease were studied in this retrospective cross-sectional study. Aortic dilatation was defined as an aortic root or ascending aortic diameter ≥45 mm. Medications were self-reported by the patients in a systematic questionnaire. Cyclooxygenase gene expression was measured in the intima-media portion of the ascending aorta (n=117). In a multivariable analysis, ASA was associated with a reduced prevalence of ascending aortic aneurysm (relative risk, 0.68 [95% CI, 0.48-0.95], P=0.026) in patients with tricuspid aortic valves, but not in patients with bicuspid aortic valves (relative risk, 0.93 [95% CI, 0.64-1.34], P=0.687). Intima-media cyclooxygenase expression was positively correlated with ascending aortic dimensions (P<0.001 for cyclooxygenase-1 and P=0.05 for cyclooxygenase-2). In dilated, but not nondilated tricuspid aortic valve aortic specimens, ASA was associated with significantly lower cyclooxygenase-2 levels (P=0.034). Conclusions Our findings are consistent with the hypothesis that ASA treatment may attenuate ascending aortic aneurysmal growth, possibly via cyclooxygenase-2 inhibition in the ascending aortic wall and subsequent anti-inflammatory actions.

Comparison of Long-term Performance of Bioprosthetic Aortic Valves in Sweden From 2003 to 2018.

IMPORTANCE: The performance of bioprosthetic aortic valves is usually assessed in single valve models or head-to-head comparisons. National databases or registries offer the opportunity to investigate all available valve models in the population and allows for a comparative assessment of their performance. OBJECTIVE: To analyze the long-term rates of reintervention, all-cause mortality, and heart failure hospitalization associated with commonly used bioprosthetic aortic valves and to identify valve model groups with deviation in clinical performance. DESIGN, SETTING, AND PARTICIPANTS: This population-based, nationwide cohort study included all adult patients who underwent surgical aortic valve replacement (with or without concomitant coronary artery bypass surgery or ascending aortic surgery) in Sweden between January 1, 2003, and December 31, 2018. Patients were identified from the SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry. Patients with concomitant valve surgery, previous cardiac surgery, and previous transcatheter valve replacement were excluded. Follow-up was complete for all participants. Data were analyzed from March 9, 2020, to October 12, 2021. EXPOSURES: Primary surgical aortic valve replacement with the Perimount, Mosaic/Hancock, Biocor/Epic, Mitroflow/Crown, Soprano, and Trifecta valve models. MAIN OUTCOMES AND MEASURES: The primary outcome was cumulative incidence of reintervention, defined as a subsequent aortic valve operation or transcatheter valve replacement. Secondary outcomes were all-cause mortality and heart failure hospitalization. Regression standardization and flexible parametric survival models were used to account for intergroup differences. Mean follow-up time was 7.1 years, and maximum follow-up time was 16.0 years. RESULTS: A total of 16 983 patients (mean [SD] age, 72.6 [8.5] years; 10 685 men [62.9%]) were included in the analysis. The Perimount valve model group had the lowest and the Mitroflow/Crown valve model group had the highest cumulative incidence of reintervention. The estimated cumulative incidence of reintervention at 10 years was 3.6% (95% CI, 3.1%-4.2%) in the Perimount valve model group and 12.2% (95% CI, 9.8%-15.1%) in the Mitroflow/Crown valve model group. The estimated incidence of reintervention at 10 years was 9.3% (95% CI, 7.3%-11.3%) in the Soprano valve model group. CONCLUSIONS AND RELEVANCE: Results of this study showed that the Perimount valve was the most commonly used and had the lowest incidence of reintervention, all-cause mortality, and heart failure hospitalization, whereas the Mitroflow/Crown valve had the highest rates. These findings highlight the need for clinical vigilance in patients who receive either a Soprano or Mitroflow/Crown aortic bioprosthesis.

Sex Differences in Aortopathy and Valve Diseases Among Patients Undergoing Cardiac Surgical Procedure.

BACKGROUND: We aimed to study sex differences in aortopathy and valve disease among patients undergoing aortic valve replacement and/or surgical procedure for ascending aortic aneurysm and assess whether differences are specific for patients with bicuspid aortic valve (BAV) compared with patients with tricuspid aortic valve. METHODS: We used a single-center and observational cohort including 1045 patients undergoing elective open heart surgical procedure for aortic valve disease and/or ascending aortic aneurysm at the Karolinska Hospital (Stockholm, Sweden). RESULTS: Women (33.0%) were older than men (mean [SD]; 67.9 [11] years vs 62.5 [13] years for men; P < .001). No significant sex difference in prevalence of ascending aortic aneurysm was found according to absolute measures (P = .19); however, women had a greater dilation of the ascending aorta when normalized for body surface area (mean, 21.8 [SD, 6.3] mm/m2 vs 19.3 [SD, 4.4] mm/m2 for men; P < .001). Among the 560 patients with BAV, women had significantly more aortic stenosis (adjusted odds ratio, 2.23; 95% CI, 1.19-4.20; P = .013) and less aortic insufficiency (adjusted odds ratio, 0.42; 95% CI, 0.23-0.78; P < .01); whereas no sex difference was found among patients with tricuspid aortic valve. CONCLUSIONS: In this large study of patients undergoing cardiac surgical procedure, we found a greater degree of aortic dilation in women compared with men, suggesting a need for earlier monitoring of women. Moreover, women with BAV had a significantly higher prevalence of aortic stenosis compared with men. These results describe the aorta and valvular characteristics of patients by sex and provide guidance regarding which patients might benefit from closer surveillance.

Metformin therapy is not associated with the lower prevalence of ascending aortic aneurysm in diabetic patients.

OBJECTIVES: Metformin therapy has previously been associated with reduced abdominal aortic aneurysm growth rate in diabetic patients and shown to suppress the formation and progression of abdominal aortic aneurysm in normoglycemic mice. Here, we investigated the association between Metformin treatment and prevalence of aneurysm in the ascending aorta (AscAA). METHODS: A total of 734 patients undergoing open-heart surgery for AscAA and/or aortic valve disease were studied. Diabetes status and medication use were self-reported by the patients in a systematic questionnaire. Aortic dilatation was defined as an aortic root or ascending aortic diameter ≥4.0 cm. High-sensitivity C-reactive protein levels were assessed as a measure of systemic inflammation. RESULTS: We could confirm the inverse association between diabetes and AscAA prevalence (16% vs 43.9%, for diabetic and non-diabetic patients, respectively; Odds ratio 0.243; 95% CI, 0.129-0.460, P < 0.001). Furthermore, in diabetic patients, Metformin treatment was associated with lower high-sensitivity C-reactive protein levels. There was, however, no difference in the prevalence of AscAA among diabetic patients with and without Metformin treatment (16% vs 16% for treated and non-treated patients, respectively; OR 1.039; 95% CI 0.26-4.19, P = 0.957). CONCLUSIONS: Our data do not support a protective effect of Metformin therapy in AscAA formation. SUBJ COLLECTION: 161, 173.

Long-term follow-up of passive containment surgery in patients with aortic regurgitation.

The goal of this case-control study was to evaluate the long-term effects on cardiac dimensions, cardiac function and coronary circulation in patients with aortic regurgitation (AR) and left ventricular dilatation undergoing aortic valve replacement and application of the Acorn CorCap cardiac support device Of 10 patients with AR and ventricular dilatation who had a mechanical aortic valve implanted, 5 in addition received the cardiac support device. Cardiac dimensions and cardiac function were measured by echocardiography preoperatively and 1, 5 and 10 years postoperatively. The coronary circulation was assessed by computed tomography angiography. After aortic valve replacement, there was a rapid and sustained decrease in cardiac dimensions. This result did not differ after application of the cardiac support device. Improvement in cardiac function remained unchanged in both groups at the 10-year follow-up. None of the patients had developed any signs of coronary artery disease. Application of the Acorn CorCap cardiac support device in patients with AR and left ventricular dilatation did not add to the reversed remodelling or cardiac function at the long-term follow-up compared to aortic valve replacement alone.

Cardiovascular Risk Factors and Hemodynamic Measures as Determinants of Increased Arterial Stiffness Following Surgical Aortic Valve Replacement.

Valvular and arterial function are tightly intertwined, both in terms of structural changes and hemodynamics. While proximal valvulo-vascular coupling contributes to the cardiovascular consequences of aortic stenosis, less is known on how peripheral arterial stiffness relates to aortic valve disease. Previous studies have shown conflicting results regarding the impact of aortic valve replacement on arterial stiffness. The aim of the present study was therefore to determine predictors of arterial stiffness in patients with and without aortic valve disease undergoing cardiac surgery. Cardio ankle vascular index (CAVI) and carotid femoral pulse wave velocity (cfPWV) were measured to determine arterial stiffness the day before and 3 days after surgery for either ascending aortic or aortic valve disease. Stratification on indication for surgery revealed that CAVI was significantly lower in patients with aortic valve stenosis (n = 45) and aortic valve regurgitation (n=30) compared with those with isolated ascending aortic dilatation (n = 13). After surgery, a significant increased CAVI was observed in aortic stenosis (median 1.34, IQR 0.74-2.26, p < 0.001) and regurgitation (median 1.04, IQR 0.01-1.49, p = 0.003) patients while cfPWV was not significantly changed. Age, diabetes, low body mass index, low pre-operative CAVI, as well as changes in ejection time were independently associated with increased CAVI after surgery. The results of the present study suggest aortic valve disease as cause of underestimation of arterial stiffness when including peripheral segments. We report cardiovascular risk factors and pinpoint the hemodynamic aspect ejection time to be associated with increased CAVI after aortic valve surgery.