Biomarkers of inflammation and coagulation after minimally invasive mitral valve surgery: a prospective comparison to conventional surgery.

OBJECTIVES: Minimally invasive cardiac surgery techniques are increasingly used but have longer cardiopulmonary bypass time, which may increase inflammatory response and negatively affect coagulation. Our aim was to compare biomarkers of inflammation and coagulation as well as transfusion rates after minimally invasive mitral valve repair and mitral valve surgery using conventional sternotomy. DESIGN: A prospective non-randomized study was performed enrolling 71 patients undergoing mitral valve surgery (35 right mini-thoracotomy and 36 conventional sternotomy procedures). Blood samples were collected pre- and postoperatively to assess inflammatory response. Thromboelastometry (ROTEM) was performed to assess coagulation, and transfusion rates were monitored. RESULTS: The minimally invasive group had longer cardiopulmonary bypass times compared to the sternotomy group: 127 min ([115-146] vs 79 min [65-112], p < 0.001) and were cooled to a lower temperature during cardiopulmonary bypass, 34 °C vs 36 °C (p = 0.04). IL-6 was lower in the minimally invasive group compared to the conventional sternotomy group when measured at the end of the surgical procedure, (38 [23-69] vs 61[41-139], p = 0.008), but no differences were found at postoperative day 1 or postoperative day 3. The transfusion rate was lower in the minimally invasive group (14%) compared to full sternotomy (35%, p = 0.04) and the chest tube output was reduced, (395 ml [190-705] vs 570 ml [400-1040], p = 0.04). CONCLUSIONS: Our data showed that despite the longer use of extra corporal circulation during surgery, minimally invasive mitral valve repair is associated with reduced inflammatory response, lower rates of transfusion, and reduced chest tube output.

Vitamin K and cancer.

Subclinical vitamin K deficits refer to carboxylation defects of different types of vitamin K-dependent hepatic and extrahepatic so-called Gla proteins without prolongation of the prothrombin time. This condition has been reported in different clinical situations due to insufficient supply or malabsorption of vitamin K as well as drug interactions. This review discusses the effects of different vitamin K subspecies on tumour growth and the possible anti-tumour effects of increased vitamin K intake. Blocking carboxylation of vitamin K-dependent proteins with warfarin anticoagulation - what are the risks/benefits for carcinogenesis? Previous studies on both heparin and low molecular weight heparin blocking of the vitamin K-dependent factors X and II have shown tumour suppressive effects. Vitamin K has anti-inflammatory effects that could also impact carcinogenesis, but little data exists on this subject.

Retrograde cerebral perfusion reduces embolic and watershed lesions after acute type a aortic dissection repair with deep hypothermic circulatory arrest.

BACKGROUND: To assess whether retrograde cerebral perfusion reduces neurological injury and mortality in patients undergoing surgery for acute type A aortic dissection. METHODS: Single-center, retrospective, observational study including all patients undergoing acute type A aortic dissection repair with deep hypothermic circulatory arrest between January 1998 and December 2022 with or without the adjunct of retrograde cerebral perfusion. 515 patients were included: 257 patients with hypothermic circulatory arrest only and 258 patients with hypothermic circulatory arrest and retrograde cerebral perfusion. The primary endpoints were clinical neurological injury, embolic lesions, and watershed lesions. Multivariable logistic regression was performed to identify independent predictors of the primary outcomes. Survival analysis was performed using Kaplan-Meier estimates. RESULTS: Clinical neurological injury and embolic lesions were less frequent in patients with retrograde cerebral perfusion (20.2% vs. 28.4%, p = 0.041 and 13.7% vs. 23.4%, p = 0.010, respectively), but there was no significant difference in the occurrence of watershed lesions (3.0% vs. 6.1%, p = 0.156). However, after multivariable logistic regression, retrograde cerebral perfusion was associated with a significant reduction of clinical neurological injury (OR: 0.60; 95% CI 0.36-0.995, p = 0.049), embolic lesions (OR: 0.55; 95% CI 0.31-0.97, p = 0.041), and watershed lesions (OR: 0.25; 95%CI 0.07-0.80, p = 0.027). There was no significant difference in 30-day mortality (12.8% vs. 11.7%, p = ns) or long-term survival between groups. CONCLUSION: In this study, we showed that the addition of retrograde cerebral perfusion during hypothermic circulatory arrest in the setting of acute type A aortic dissection repair reduced the risk of clinical neurological injury, embolic lesions, and watershed lesions.

Mortality after non-surgically treated acute type A aortic dissection is higher than previously reported.

OBJECTIVES: It has been commonly accepted that untreated acute type A aortic dissection (ATAAD) results in an hourly mortality rate of 1-2% during the 1st 24 h after symptom onset. The data to support this statement rely solely on patients who have been denied surgical treatment after reaching surgical centres. The objective was to perform a total review of non-surgically treated (NST) ATAAD and provide contemporary mortality data. METHODS: This was a regional, retrospective, observational study. All patients receiving one of the following diagnoses: International Classification of Diseases (ICD)-9 4410, 4411, 4415, 4416 or ICD-10 I710, I711, I715, I718 in an area of 1.9 million inhabitants in Southern Sweden during a period of 23 years (January 1998 to November 2021) were retrospectively screened. The search was conducted using all available medical registries so that every patient diagnosed with ATAAD in our region was identified. The charts and imaging of each screened patient were subsequently reviewed to confirm or discard the diagnosis of ATAAD. RESULTS: Screening identified 2325 patients, of whom 184 NST ATAAD patients were included. The mortality of NST ATAAD was 47.3 ± 4.4%, 55.0 ± 4.4%, 76.7 ± 3.7% and 83.9 ± 4.3% at 24 h, 48 h, 14 days and 1 year, respectively. The hourly mortality rate during the 1st 24 h after symptom onset was 2.6%. CONCLUSIONS: This study observed higher mortality than has previously been reported. It emphasizes the need for timely diagnosis, swift management and emergent surgical treatment for patients suffering an acute type A aortic dissection.

Myocardin related transcription factor and galectin-3 drive lipid accumulation in human blood vessels.

OBJECTIVE: Diabetes and hypertension are important risk factors for vascular disease, including atherosclerosis. A driving factor in this process is lipid accumulation in smooth muscle cells of the vascular wall. The glucose- and mechano-sensitive transcriptional coactivator, myocardin-related transcription factor A (MRTF-A/MKL1) can promote lipid accumulation in cultured human smooth muscle cells and contribute to the formation of smooth muscle-derived foam cells. The purpose of this study was to determine if intact human blood vessels ex vivo can be used to evaluate lipid accumulation in the vascular wall, and if this process is dependent on MRTF and/or galectin-3/LGALS3. Galectin-3 is an early marker of smooth muscle transdifferentiation and a potential mediator for foam cell formation and atherosclerosis. APPROACH AND RESULTS: Human mammary arteries and saphenous veins were exposed to altered cholesterol and glucose levels in an organ culture model. Accumulation of lipids, quantified by Oil Red O, was increased by cholesterol loading and elevated glucose concentrations. Pharmacological inhibition of MRTF with CCG-203971 decreased lipid accumulation, whereas adenoviral-mediated overexpression of MRTF-A had the opposite effect. Cholesterol-induced expression of galectin-3 was decreased after inhibition of MRTF. Importantly, pharmacological inhibition of galectin-3 with GB1107 reduced lipid accumulation in the vascular wall after cholesterol loading. CONCLUSION: Ex vivo organ culture of human arteries and veins can be used to evaluate lipid accumulation in the intact vascular wall, as well as adenoviral transduction and pharmacological inhibition. Although MRTF and galectin-3 may have beneficial, anti-inflammatory effects under certain circumstances, our results, which demonstrate a significant decrease in lipid accumulation, support further evaluation of MRTF- and galectin-3-inhibitors for therapeutic intervention against atherosclerotic vascular disease.

Limited Distal Repair Results in Low Rates of Distal Events Following Surgery for Acute Type A Aortic Dissection.

To investigate mortality and reoperation rates following limited distal repair after acute type A aortic dissection (ATAAD) at a single medium volume institution. We analyzed all patients that underwent limited distal repair (ascending aortic or hemiarch replacement) following ATAAD between January 1998 and April 2020 at our institution. During the study period, 489 patients underwent ATAAD surgery, of which 457 (94%) underwent limited distal repair with a 30-day mortality of 12.9%. Among 30-day survivors, late follow-up was 97.7% complete with a mean follow-up of 6.0 ± 5.5 years. In all, 50 patients (11%) required a reoperation during the study period at a mean of 3.4 ± 3.4 years after initial repair, with a 30-day mortality of 12%. An aortic reoperation was required in 4.1 (2.0-6.1)%, 10.3 (7.1-13.6)%, 15.1 (10.9-19.4)%, and 18.0 (13.0-22.9)% of patients at 1, 5, 10, and 15 years. A distal reoperation was required in 3.0 (1.2-4.7)%, 8.0 (5.1-10.9)%, 10.3 (6.8-13.8)%, and 12.4 (8.2-16.5)% of patients and 4.4 (2.3-6.4)%, 10.4 (7.1-13.7)%, 13.9 (9.8-18.0)%, and 16.9 (12.0-21.9)% of patents had a distal event at 1, 5, 10, and 15 years, respectively. Limited distal repair with an ascending aortic or hemiarch replacement was associated with acceptable survival and rates of reoperations and distal events. Limited distal repair is a safe and feasible standard approach to ATAAD surgery at a medium-volume center.

S100B predicts neurological injury and 30-day mortality following surgery for acute type A aortic dissection: an observational cohort study.

BACKGROUND: Neurological injuries are frequent following Acute Type A Aortic Dissection (ATAAD) repair occurring in 4-30% of all patients. Our objective was to study whether S100B can predict neurological injury following ATAAD repair. METHODS: This was a single-center, retrospective, observational study. The study included all patients that underwent ATAAD repair at our institution between Jan 1998 and Dec 2021 and had recorded S100B-values. The primary outcome measure was neurological injury, defined as focal neurological deficit or coma diagnosed by clinical assessment with or without radiological confirmation and with a symptom duration of more than 24 h. Secondary outcome measure was 30-day mortality. RESULTS: 538 patients underwent surgery during the study period and 393 patients, had recorded S100B-values. The patients had a mean age of 64.4 ± 11.1 years and 34% were female. Receiver operating characteristic curve for S100B 24 h postoperatively yielded area under the curve 0.687 (95% CI 0.615-0.759) and best Youden's index corresponded to S100B 0.225 which gave a sensitivity of 60% and specificity of 75%. Multivariable logistic regression identified S100B ≥ 0.23 µg/l at 24 h as an independent predictor for neurological injury (OR 4.71, 95% CI 2.59-8.57; p < 0.01) along with preoperative cerebral malperfusion (OR 4.23, 95% CI 2.03-8.84; p < 0.01) as well as an independent predictor for 30-day mortality (OR 4.57, 95% CI 1.18-11.70; p < 0.01). CONCLUSIONS: We demonstrated that S100B, 24 h after surgery is a strong independent predictor for neurological injury and 30-day mortality after ATAAD repair. TRIAL REGISTRATION: As this was a retrospective observational study it was not registered.

Radiological properties of neurological injury following acute type A aortic dissection repair.

Objective: The study objective was to assess the radiological properties of acute type A aortic dissection-related neurological injuries and identify predictors of neurological injury. Methods: Our single-center, retrospective, observational study included all patients who underwent acute type A aortic dissection repair between January 1998 and December 2021. Multivariable analyses and Cox regression were performed to identify predictors of embolic lesions, watershed lesions, neurological injury, 30-day mortality, and late mortality. Results: A total of 538 patients were included. Of these, 120 patients (22.3%) experienced postoperative neurological injury; 74 patients (13.8%) had postoperative stroke, and 36 patients (6.8%) had postoperative coma. The 30-day mortality was 22.7% in the neurological injury group versus 5.8% in the no neurological injury group (P < .001). We identified several independent predictors of neurological injury. Cerebral malperfusion (odds ratio, 2.77; 95% confidence interval, 1.53-5.00), systemic hypotensive shock (odds ratio, 1.97; 95% confidence interval, 1.13-3.43), and aortic arch replacement (odds ratio, 3.08; 95% confidence interval, 1.17-8.08) predicted embolic lesions. Diabetes mellitus (odds ratio, 5.35; 95% confidence interval, 1.85-15.42), previous cardiac surgery (odds ratio, 8.62; 95% confidence interval, 1.47-50.43), duration of hypothermic circulatory arrest (odds ratio, 1.05; 95% confidence interval, 1.01-1.08), cardiopulmonary bypass time (odds ratio, 1.01; 95% confidence interval, 1.00-1.01), ascending aortic/arch cannulation (odds ratio, 5.68; 95% confidence interval, 1.88-17.12), and left ventricular cannulation (odds ratio, 17.81; 95% confidence interval, 1.69-188.01) predicted watershed lesions. Retrograde cerebral perfusion (odds ratio, 0.28; 95% confidence interval, 0.01-0.84) had a protective effect against watershed lesions. Conclusions: In this study, we demonstrated that the radiological features of neurological injury may be as important as clinical characteristics in understanding the pathophysiology and causality behind neurological injury related to acute type A aortic dissection repair.

Type A Aortic Dissection Repair in Patients With Prior Cardiac Surgery.

BACKGROUND: Emergency surgery for acute type A aortic dissection in patients with previous cardiac surgery is controversial. This study aimed to evaluate the association between previous cardiac surgery and outcomes after surgery for acute type A aortic dissection, to appreciate whether emergency surgery can be offered with acceptable risks. METHODS: All patients operated on for acute type A aortic dissection between 2005 and 2014 from the Nordic Consortium for Acute Type A Aortic Dissection database were eligible. Patients with previous cardiac surgery were compared with patients without previous cardiac surgery. Univariable and multivariable statistical analyses were performed to identify predictors of 30-day mortality and early major adverse events (a secondary composite endpoint comprising 30-day mortality, perioperative stroke, postoperative cardiac arrest, or de novo dialysis). RESULTS: In all, 1159 patients were included, 40 (3.5%) with previous cardiac surgery. Patients with previous cardiac surgery had higher 30-day mortality (30% vs 17.8%, P = .049), worse medium-term survival (51.7% vs 71.2% at 5 years, log rank P = .020), and higher unadjusted prevalence of major adverse events (52.5% vs 35.7%, P = .030). In multivariable analysis, previous cardiac surgery was not associated with 30-day mortality (odds ratio 0.78; 95% CI, 0.30-2.07; P = .624) or major adverse events (odds ratio 1.07; 95% CI, 0.45-2.55, P = .879). CONCLUSIONS: Major adverse events after surgery for acute type A aortic dissection were more frequent in patients with previous cardiac surgery. Previous cardiac surgery itself was not an independent predictor for adverse events, although the small sample size precludes definite conclusions. Previous cardiac surgery should not deter from emergency surgery.

Carbon dioxide flooding to reduce postoperative neurological injury following surgery for acute type A aortic dissection: a prospective, randomised, blinded, controlled clinical trial, CARTA study protocol - objectives and design.

INTRODUCTION: Neurological complications after surgery for acute type A aortic dissection (ATAAD) increase patient morbidity and mortality. Carbon dioxide flooding is commonly used in open-heart surgery to reduce the risk of air embolism and neurological impairment, but it has not been evaluated in the setting of ATAAD surgery. This report describes the objectives and design of the CARTA trial, investigating whether carbon dioxide flooding reduces neurological injury following surgery for ATAAD. METHODS AND ANALYSIS: The CARTA trial is a single-centre, prospective, randomised, blinded, controlled clinical trial of ATAAD surgery with carbon dioxide flooding of the surgical field. Eighty consecutive patients undergoing repair of ATAAD, and who do not have previous neurological injuries or ongoing neurological symptoms, will be randomised (1:1) to either receive carbon dioxide flooding of the surgical field or not. Routine repair will be performed regardless of the intervention. The primary endpoints are size and number of ischaemic lesions on brain MRI performed after surgery. Secondary endpoints are clinical neurological deficit according to the National Institutes of Health Stroke Scale, level of consciousness using the Glasgow Coma Scale motor score, brain injury markers in blood after surgery, neurological function according to the modified Rankin Scale and postoperative recovery 3 months after surgery. ETHICS AND DISSEMINATION: Ethical approval has been granted by Swedish Ethical Review Agency for this study. Results will be disseminated through peer-reviewed media. TRIAL REGISTRATION NUMBER: NCT04962646.

Desphospho-Uncarboxylated Matrix-Gla Protein Is Increased Postoperatively in Cardiovascular Risk Patients.

BACKGROUND: Matrix Gla protein (MGP) is an extrahepatic protein that is dependent on glutamate carboxylation, a vitamin K-dependent process. Its dysfunctional form, desphospho-uncarboxylated-MGP, has been associated with increased arterial calcification and stiffness. The aim of this study was to measure the degree of postoperative carboxylation of MGP and two other Gla proteins in patients scheduled for abdominal or orthopaedic surgery. METHODS: Forty patients undergoing abdominal or orthopaedic surgery were included. Blood samples were collected preoperatively and four days after the surgery. Desphospho-carboxylated MGP (dp-cMGP), desphospho-uncarboxylated MGP (dp-ucMGP), carboxylated osteocalcin (OC) (cOC), uncarboxylated OC (ucOC), and uncarboxylated prothrombin (PIVKA-II) were analysed. RESULTS: Preoperatively, 29 patients had dp-ucMGP levels above the reference values. Patients with pre-existing cardiovascular comorbidities had higher dp-ucMGP preoperatively compared with patients with no record of cardiovascular disease. Postoperatively, this number increased to 36 patients, and median dp-ucMGP levels increased (p < 0.0001) and correlated to a PIVKA-II increase (r = 0.44). On the other hand, dp-cMGP levels did not significantly alter. Decreased levels of ucOC and cOC were seen after surgery (p = 0.017 and p = 0.0033, respectively). Comorbidities, possible nutritional defects, and complications affecting Gla protein activity and function were identified. CONCLUSIONS: Dp-ucMGP was high preoperatively, and had further increased postoperatively. This pattern was linked to several comorbidities, possible nutritional defects, and postoperative complications, which motivates further research about potential interactions between perioperative corrective treatments with vitamin K supplements, cardiovascular biomarkers, and incidents of stroke and myocardial infarction events.