[Perioperative stroke after aortic valve replacement for aortic stenosis - incidence, risk factors and short-term outcome].

INTRODUCTION: One of the most serious complications of surgical aortic valve replacement (SAVR) is stroke that can result in increased rates of complications, morbidity and mortality postoperatively. The aim of this study was to investigate incidence, risk factors and short-term outcome in a well defined cohort of SAVR-patients. MATERIALS AND METHOD: A retrospective study on 740 consecutive aortic stenosis patients who underwent SAVR in Iceland 2002-2019. Patients with stroke were compared with non-stroke patients; including preoperative risk factors of cardiovascular disease, echocardiogram-results, rate of early postoperative complications other than stroke and 30 day mortality. RESULTS: Mean age was 71 yrs (34% females) with 57% of the patients receiving stented bioprosthesis, 31% a stentless Freestyle®-valve and 12% a mechanical valve. Mean EuroSCORE-II was 3.6, with a maximum preop-gradient of 70 mmHg and an estimated valvular area of 0.73 cm2. Thirteen (1.8%) patients were diagnosed with stroke where hemiplegia (n=9), loss of consciousness (n=3) and/or aphasia (n=4) were the most common presenting symptoms. In 70% of cases the neurological symptoms resolved or disappeared in the first weeks and months after surgery. Only one patient out of 13 died within 30-days (7.7%). Stroke-patients had significantly lower BMI than non-stroke patients, but other risk factors of cardiovascular diseases, intraoperative factors or the rate of other severe postoperative complications than stroke were similar between groups. Total length of stay was 14 days vs. 10 days median, including 2 vs. 1 days in the ICU, in the stroke and non-stroke-groups, respectively. CONCLUSIONS: The rate of stroke after SAVR was low (1.8%) and in line with other similar studies. Although a severe complication, most patients with perioperative stroke survived 30 days postoperatively and in majority of cases neurological symptoms recovered.

Recurrence of Atrial Fibrillation in Patients With New-Onset Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting.

Importance: New-onset postoperative atrial fibrillation (POAF) occurs in approximately 30% of patients undergoing coronary artery bypass grafting (CABG). It is unknown whether early recurrence is associated with worse outcomes. Objective: To test the hypothesis that early AF recurrence in patients with POAF after CABG is associated with worse outcomes. Design, Setting, and Participants: This Swedish nationwide cohort study used prospectively collected data from the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry and 3 other mandatory national registries. The study included patients who underwent isolated first-time CABG between January 1, 2007, and December 31, 2020, and developed POAF. Data analysis was performed between March 6 and September 16, 2023. Exposure: Early AF recurrence defined as an episode of AF leading to hospital care within 3 months after discharge. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes included ischemic stroke, any thromboembolism, heart failure hospitalization, and major bleeding within 2 years after discharge. The groups were compared with multivariable Cox regression models, with early AF recurrence as a time-dependent covariate. The hypothesis tested was formulated after data collection. Results: Of the 35 329 patients identified, 10 609 (30.0%) developed POAF after CABG and were included in this study. Their median age was 71 (IQR, 66-76) years. The median follow-up was 7.1 (IQR, 2.9-9.0) years, and most patients (81.6%) were men. Early AF recurrence occurred in 6.7% of patients. Event rates (95% CIs) per 100 patient-years with vs without early AF recurrence were 2.21 (1.49-3.24) vs 2.03 (1.83-2.25) for all-cause mortality, 3.94 (2.92-5.28) vs 2.79 (2.56-3.05) for heart failure hospitalization, and 3.97 (2.95-5.30) vs 2.74 (2.51-2.99) for major bleeding. No association between early AF recurrence and all-cause mortality was observed (adjusted hazard ratio [AHR], 1.17 [95% CI, 0.80-1.74]; P = .41). In exploratory analyses, there was an association with heart failure hospitalization (AHR, 1.80 [95% CI, 1.32-2.45]; P = .001) and major bleeding (AHR, 1.92 [1.42-2.61]; P < .001). Conclusions and Relevance: In this cohort study of early AF recurrence after POAF in patients who underwent CABG, no association was found between early AF recurrence and all-cause mortality. Exploratory analyses showed associations between AF recurrence and heart failure hospitalization, oral anticoagulation, and major bleeding.

[Incidence and outcomes of perioperative myocardial infarction associated with coronary artery bypass surgery].

INTRODUCTION: Perioperative myocardial infarction (PMI) after CABG can contribute to in-hospital morbidity and mortality, however, its clinical significance on long-term outcome, remains inadequately addressed. We studied both 30-day mortality and long-term effects of PMI in Icelandic CABG-patients. MATERIALS AND METHODS: A retrospective nationwide-study on 1446 consecutive CABG-patients operated at Landspitali in Iceland 2002-2018 without evidence of preoperative myocardial infarction. PMI was defined as a tenfold elevetion in serum-CK-MB associated with new ECG changes or diagnostic imaging consistent with ischemia. Patients with PMI were compared to a reference group with uni- and multivariate analyses. Long-term and MACCE-free survival were estimated with the Kaplan-Meier method and logistic regression used to determine factors associated with PMI. The mean follow-up time was 8.3 years. RESULTS: Out of 1446 patients 78 (5.4%) were diagnosed with PMI (range: 0-15.5%) with a significant annual decline in the incidence of PMI (12.7%, p<0.001). Over the same period preoperative aspirin use increased by 22.3% (p<0.018). PMI patients had a higher rate of short-term complications and a 11.5% 30-day mortality rate compared to 0.4% for non-PMI patients. PMI was found to be a predictor of 30-day mortality (OR 15.44, 95% CI: 6.89-34.67). PMI patients had worse 5-year MACCE-free survival (69.2% vs. 84.7, p=0,01), although overall survival was comparable between the groups. CONCLUSIONS: Although PMI after CABG is associated with significantly higher rates of short-term complications and 30-day mortality, long-term survival was similar to the reference group. Therefore, the mortality risk attributable to PMI appears to diminish after the immediate postoperative period.

Statin treatment after surgical aortic valve replacement for aortic stenosis is associated with better long-term outcome.

OBJECTIVES: The aim of this study was to evaluate the association between statin use after surgical aortic valve replacement for aortic stenosis and long-term risk for major adverse cardiovascular events (MACEs) in a large population-based, nationwide cohort. METHODS: All patients who underwent isolated surgical aortic valve replacement due to aortic stenosis in Sweden 2006-2020 and survived 6 months after discharge were included. Individual patient data from 5 nationwide registries were merged. Primary outcome is MACE (defined as all-cause mortality, myocardial infarction or stroke). Multivariable Cox regression model adjusted for age, sex, comorbidities, valve type, operation year and secondary prevention medications is used to evaluate the association between time-updated dispense of statins and long-term outcome in the entire study population and in subgroups based on age, sex and comorbidities. RESULTS: A total of 11 894 patients were included. Statins were dispensed to 49.8% (5918/11894) of patients at baseline, and 51.0% (874/1713) after 10 years. At baseline, 3.6% of patients were dispensed low dose, 69.4% medium dose and 27.0% high-dose statins. After adjustments, ongoing statin treatment was associated with a reduced risk for MACE [adjusted hazard ratio 0.77 (95% confidence interval 0.71-0.83). P < 0.001], mainly driven by a reduction in all-cause mortality [adjusted hazard ratio, 0.70 (0.64-0.76)], P < 0.001. The results were consistent in all subgroups. CONCLUSIONS: The results suggest that statin therapy might be beneficial for patients undergoing surgical aortic valve replacement for aortic stenosis. Randomized controlled trials are warranted to establish causality between statin treatment and improved outcome.

Cardiopulmonary bypass management and acute kidney injury in cardiac surgery patients.

BACKGROUND: Cardiopulmonary bypass (CPB) ensures tissue oxygenation during cardiac surgery. New technology allows continuous registration of CPB variables during the operation. The aim of the present investigation was to study the association between CPB management and the risk of postoperative acute kidney injury (AKI). METHODS: This observational study based on prospectively registered data included 2661 coronary artery bypass grafting and/or valve patients operated during 2016-2020. Individual patient characteristics and postoperative outcomes collected from the SWEDEHEART registry were merged with CPB variables automatically registered every 20 s during CPB. Associations between CPB variables and AKI were analyzed with multivariable logistic regression models adjusted for patient characteristics. RESULTS: In total, 387 patients (14.5%) developed postoperative AKI. After adjustments, longer time on CPB and aortic cross-clamp, periods of compromised blood flow during aortic cross-clamp time, and lower nadir hematocrit were associated with the risk of AKI, while mean blood flow, bladder temperature, central venous pressure, and mixed venous oxygen saturation were not. Patient characteristics independently associated with AKI were advanced age, higher body mass index, hypertension, diabetes mellitus, atrial fibrillation, lower left ventricular ejection fraction, estimated glomerular filtration rate <60 or >90 mL/min/m2 , and preoperative hemoglobin concentration below or above the normal sex-specific range. CONCLUSIONS: To reduce the risk of AKI after cardiac surgery, aortic clamp time and CPB time should be kept short, and low hematocrit and periods of compromised blood flow during aortic cross-clamp time should be avoided if possible.

Renin-angiotensin system inhibition after surgical aortic valve replacement for aortic stenosis.

OBJECTIVE: The optimal medical therapy after surgical aortic valve replacement (SAVR) for aortic stenosis remains unknown. Renin-angiotensin system (RAS) inhibitors could potentially improve cardiac remodelling and clinical outcomes after SAVR. METHODS: All patients undergoing SAVR due to aortic stenosis in Sweden 2006-2020 and surviving 6 months after surgery were included. The primary outcome was major adverse cardiovascular events (MACEs; all-cause mortality, stroke or myocardial infarction). Secondary endpoints included the individual components of MACE and cardiovascular mortality. Time-updated adjusted Cox regression models were used to compare patients with and without RAS inhibitors. Subgroup analyses were performed, as well as a comparison between angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). RESULTS: A total of 11 894 patients (mean age, 69.5 years, 40.4% women) were included. Median follow-up time was 5.4 (2.7-8.5) years. At baseline, 53.6% of patients were dispensed RAS inhibitors, this proportion remained stable during follow-up. RAS inhibition was associated with a lower risk of MACE (adjusted hazard ratio (aHR) 0.87 (95% CI 0.81 to 0.93), p<0.001), mainly driven by a lower risk of all-cause death (aHR 0.79 (0.73 to 0.86), p<0.001). The lower MACE risk was consistent in all subgroups except for those with mechanical prostheses (aHR 1.07 (0.84 to 1.37), p for interaction=0.040). Both treatment with ACE inhibitors (aHR 0.89 (95% CI 0.82 to 0.97)) and ARBs (0.87 (0.81 to 0.93)) were associated with lower risk of MACE. CONCLUSION: The results of this study suggest that medical therapy with an RAS inhibitor after SAVR is associated with a 13% lower risk of MACE and a 21% lower risk of all-cause death.

Postdischarge major bleeding, myocardial infarction, and mortality risk after coronary artery bypass grafting.

OBJECTIVE: To investigate the incidence and mortality risk associated with postdischarge major bleeding after coronary artery bypass grafting (CABG), and relate this to the incidence of, and mortality risk from, postdischarge myocardial infarction. METHODS: All patients undergoing first-time isolated CABG in Sweden in 2006-2017 and surviving 14 days after hospital discharge were included in a cohort study. Individual patient data from the SWEDEHEART Registry and five other mandatory nationwide registries were merged. Piecewise Cox proportional hazards models were used to investigate associations between major bleeding, defined as hospitalisation for bleeding, with subsequent mortality risk. Similar Cox proportional hazards models were used to investigate the association between postdischarge myocardial infarction and mortality risk. RESULTS: Among 36 633 patients, 2429 (6.6%) had a major bleeding event and 2231 (6.1%) had a myocardial infarction. Median follow-up was 6.0 (range 0-11) years. Major bleeding was associated with higher mortality risk <30 days (adjusted HR (aHR)=20.2 (95% CI 17.3 to 23.5)), 30-365 days (aHR=3.8 (95% CI 3.4 to 4.3)) and >365 days (aHR=1.8 (95% CI 1.7 to 2.0)) after the event. Myocardial infarction was associated with higher mortality risk <30 days (aHR=20.0 (95% CI 16.7 to 23.8)), 30-365 days (aHR=4.1 (95% CI 3.6 to 4.8)) and >365 days (aHR=1.8 (95% CI 1.7 to 2.0)) after the event. CONCLUSIONS: The increase in mortality risk associated with a postdischarge major bleeding after CABG is substantial and is similar to the mortality risk associated with a postdischarge myocardial infarction.

[New-onset postoperative atrial fibrillation following coronary artery bypass grafting: Incidence, clinical course and short-term outcomes].

INTRODUCTION: The aims of this retrospective study were to investigate the incidence, clinical course and short term outcomes of new-onset postoperative atrial fibrillation (POAF) following coronary artery bypass surgery (CABG). MATERIALS AND METHODS: A nation-wide study on 1622 patients who underwent CABG from 2006-2020 at Landspitali University Hospital. Clinical data were extracted from registries and 121 patients with pre-existing AF excluded, leaving 1501 patients for further analysis. Patient charts and postoperative ECGs were manually reviewed for determining details of POAF, which was defined as a postoperative episode of AF before discharge lasting at least 5 minutes. Patients with POAF (n=483) were compared to non-POAF patients (n=1018). RESULTS: Altogether 483 (32.2%) patients developed POAF; the annual incidence decreasing over time (tau= -0,45, p=0.023). Most patients were diagnosed on the second day postoperatively (43.5%) and over 90% were diagnosed within 4 days. The median number of POAF episodes was 3 (IQR: 1-5), the first episode lasting 1-6 hours in half of the cases and the total POAF-duration being 12 hours median (IQR: 5-30). Over 94% of cases converted to sinus rythm before discharge, with 25 (5.3%) patients being discharged in AF. Most patients were treated with beta-blockers (98.8%), amiodarone (95%) and 14.9% with electric cardioversion. POAF-patients were older, had higher EuroSCORE II and a longer hospital stay, however, they had similar rates of early postoperative stroke and 30 day mortality. CONCLUSION: The incidence of POAF remains high and was associated with prolonged hospital stay, but not significantly higher 30 day mortality or early postoperative stroke compared to patients in sinus rhythm. POAF-episodes were predominantly transient and almost 95% of patients were discharged in sinus rythm.

Cardiopulmonary bypass management and risk of new-onset atrial fibrillation after cardiac surgery.

OBJECTIVES: Cardiopulmonary bypass (CPB) management may potentially play a role in the development of new-onset atrial fibrillation (AF) after cardiac surgery. The aim of this study was to explore this potential association. METHODS: Patients who underwent coronary artery bypass grafting and/or valvular surgery during 2016-2020 were included in an observational single-centre study. Data collected from the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry and a local CPB database were merged. Associations between individual CPB variables (CPB and aortic clamp times, arterial and central venous pressure, mixed venous oxygen saturation, blood flow index, bladder temperature and haematocrit) and new-onset AF were analysed using multivariable logistic regression models adjusted for patient characteristics, comorbidities and surgical procedure. RESULTS: Out of 1999 patients, 758 (37.9%) developed new-onset AF. Patients with new-onset postoperative AF were older, had a higher incidence of previous stroke, worse renal function and higher EuroSCORE II and CHA2DS2-VASc scores and more often underwent valve surgery. Longer CPB time [adjusted odds ratio 1.05 per 10 min (95% confidence interval 1.01-1.08); P = 0.008] and higher flow index [adjusted odds ratio 1.21 per 0.2 l/m2 (95% confidence interval 1.02-1.42); P = 0.026] were associated with an increased risk for new-onset AF, while the other variables were not. A sensitivity analysis only including patients with isolated coronary artery bypass grafting supported the primary analyses. CONCLUSIONS: CPB management following current guideline recommendations appears to have minor or no influence on the risk of developing new-onset AF after cardiac surgery.

PCI or CABG for left main coronary artery disease: the SWEDEHEART registry.

AIMS: An observational nationwide all-comers prospective register study to analyse outcomes after coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in unprotected left main coronary artery (LMCA) disease. METHODS AND RESULTS: All patients undergoing coronary angiography in Sweden are registered in the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry. Between 01/01/2005 and 12/31/2015, 11 137 patients with LMCA disease underwent CABG (n = 9364) or PCI (n = 1773). Patients with previous CABG, ST-elevation myocardial infarction (MI) or cardiac shock were excluded. Death, MI, stroke, and new revascularization during follow-up until 12/31/2015 were identified using national registries. Cox regression with inverse probability weighting (IPW) and an instrumental variable (IV), administrative region, were used. Patients undergoing PCI were older, had higher prevalence of comorbidity but lower prevalence of three-vessel disease. PCI patients had higher mortality than CABG patients after adjustments for known cofounders with IPW analysis (hazard ratio [HR] 2.0 [95% confidence interval (CI) 1.5-2.7]) and known/unknown confounders with IV analysis (HR 1.5 [95% CI 1.1-2.0]). PCI was associated with higher incidence of major adverse cardiovascular and cerebrovascular events (MACCE; death, MI, stroke, or new revascularization) than CABG, with IV analysis (HR 2.8 [95% CI 1.8-4.5]). There was a quantitative interaction for diabetic status regarding mortality (P = 0.014) translating into 3.6 years (95% CI 3.3-4.0) longer median survival time favouring CABG in patients with diabetes. CONCLUSION: In this non-randomized study, CABG in patients with LMCA disease was associated with lower mortality and fewer MACCE compared to PCI after multivariable adjustment for known and unknown confounders.

The left atrial appendage closure by surgery-2 (LAACS-2) trial protocol rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk.

BACKGROUND: Current recommendations regarding the use of surgical left atrial appendage (LAA) closure to prevent thromboembolisms lack high-level evidence. Patients undergoing open-heart surgery often have several cardiovascular risk factors and a high occurrence of postoperative atrial fibrillation (AF)-with a high recurrence rate-and are thus at a high risk of stroke. Therefore, we hypothesized that concomitant LAA closure during open-heart surgery will reduce mid-term risk of stroke independently of preoperative AF status and CHA2DS2-VASc score. METHODS: This protocol describes a randomized multicenter trial. Consecutive participants ≥18 years scheduled for first-time planned open-heart surgery from cardiac surgery centers in Denmark, Spain, and Sweden are included. Both patients with a previous diagnosis of paroxysmal or chronic AF, as well as those without AF, are eligible to participate, irrespective of their CHA2DS2-VASc score. Patients already planned for ablation or LAA closure during surgery, with current endocarditis, or where follow-up is not possible are considered noneligible. Patients are stratified by site, surgery type, and preoperative or planned oral anticoagulation treatment. Subsequently, patients are randomized 1:1 to either concomitant LAA closure or standard care (ie, open LAA). The primary outcome is stroke, including transient ischemic attack, as assigned by 2 independent neurologists blinded to the treatment allocation. To recognize a 60% relative risk reduction of the primary outcome with LAA closure, 1,500 patients are randomized and followed for 2 years (significance level of 0.05 and power of 90%). CONCLUSIONS: The LAACS-2 trial is likely to impact the LAA closure approach in most patients undergoing open-heart surgery. TRIAL REGISTRATION: NCT03724318.

[Analysis with viscoelastic hemostatic assays - a guide]. / En guide till koagulationsanalys med viskoelastiska instrument.

Viscoelastic hemostasis analyses (VHA) are a complement in the evaluation of hemostasis in patients with major bleeding. The analysis measures viscoelastic changes in whole blood and the results give an overview of several components of hemostasis. VHA can be used to optimize fibrinogen levels, platelet and plasma substitution. The main clinical evidence supporting this strategy is in trauma, obstetric bleeding, heart and liver surgery, where algorithms based on VHA results facilitate individualized therapy. VHA measurement is of limited value to exclude treatment with anticoagulants and platelet inhibitors. Quality control aspects are also more cumbersome since whole blood with limited sustainability is used. Newer, more automated versions of the instruments have increased the reproducibility. The main advantage of VHA is the fast turn-around time and their role in guiding treatment in an emergency situation with bleeding.

Associations between new-onset postoperative atrial fibrillation and long-term outcome in patients undergoing surgical aortic valve replacement.

OBJECTIVES: Data on prognostic implications of new-onset postoperative atrial fibrillation (POAF) after surgical aortic valve replacement (SAVR) is limited. We sought to explore associations between POAF, early initiated oral anticoagulation (OAC) and long-term outcome after SAVR and combined SAVR + coronary artery bypass grafting (CABG). METHODS: This is a retrospective, population-based study including all isolated SAVR (n = 7038) and combined SAVR and CABG patients (n = 3854) without a history of preoperative atrial fibrillation (AF) in Sweden 2007-2017. Individual patient data were merged from 4 nationwide registries. Inverse probability of treatment weighting-adjusted Cox regression models were employed separately in SAVR and SAVR + CABG patients. The median follow-up time was 4.7 years (range 0-10 years). RESULTS: POAF occurred in 44.5% and 50.7% of SAVR and SAVR + CABG patients, respectively. In SAVR patients, POAF was associated with increased long-term risk of death [adjusted hazard ratio (aHR) 1.21 (95% confidence interval 1.06-1.37)], ischaemic stroke [aHR 1.32 (1.08-1.59)], any thromboembolism, heart failure hospitalization and recurrent AF. In SAVR + CABG, POAF was associated with death [aHR 1.31 (1.14-1.51)], recurrent AF and heart failure, but not with ischaemic stroke [aHR 1.04 (0.84-1.29)] or thromboembolism. OAC was dispensed within 30 days after discharge to 67.0% and 65.9%, respectively, of SAVR and SAVR + CABG patients with POAF. Early initiated OAC was not associated with reduced risk of death, ischaemic stroke or thromboembolism in any group of patients. CONCLUSIONS: POAF after SAVR is associated with an increased risk of long-term mortality and morbidity. Further studies are warranted to clarify the role of OAC in SAVR patients with POAF.

Medical therapy after surgical aortic valve replacement for aortic regurgitation.

OBJECTIVES: Current clinical guidelines have no specific recommendations regarding medical therapy after surgical aortic valve replacement in patients with aortic regurgitation (AR). We studied the association between medical therapy with renin-angiotensin system (RAS) inhibitors, statins and ß-blockers and long-term major adverse cardiovascular events. METHODS: All patients undergoing valve replacement due to AR between 2006 and 2017 in Sweden and alive 6 months after discharge were included. Time-dependent multivariable Cox regression models adjusted for age, sex, patient characteristics, comorbidities, other medications and year of surgical aortic valve replacement were used. Primary outcome was a composite of all-cause mortality, myocardial infarction and stroke. Subgroup analyses based on age, sex, heart failure, low ejection fraction, hyperlipidaemia and hypertension were performed. RESULTS: A total of 2204 patients were included [median follow-up 5.0 years (range 0.0-11.5)]. At baseline, 68% of the patients were dispensed RAS inhibitors, 80% ß-blockers and 35% statins. Dispense of RAS inhibitors and ß-blockers declined over time, especially during the first year after baseline, while dispense of statins remained stable. Treatment with RAS inhibitors or statins was associated with a reduced risk of the primary outcome [adjusted hazard ratio (aHR) 0.71, 95% confidence interval (CI) 0.57-0.87 and aHR 0.78, 95% CI 0.62-0.99, respectively]. The results were consistent in subgroups based on age, sex and comorbidities. ß-Blocker treatment was associated with an increased risk for the primary outcome (aHR 1.35, 95% CI 1.07-1.70). CONCLUSIONS: The results indicate a potential beneficial association of RAS inhibitors and statins as part of a secondary preventive treatment regime after aortic valve replacement in patients with AR. The role of ß-blockers needs to be further investigated.

Hemostatic effects of a dextran-based priming solution for cardiopulmonary bypass: A secondary analysis of a randomized clinical trial.

INTRODUCTION: Intravascular fluids administered to patients may influence hemostasis. In patients undergoing cardiac surgery with cardiopulmonary bypass, the heart-lung machine is primed with 1300 ml of fluid. We assessed postoperative coagulation and platelet function in patients randomized to two different priming solutions, one colloid-based (dextran 40) and one crystalloid-based. MATERIALS AND METHODS: Eighty-four elective cardiac surgery patients were randomized to either a dextran-based prime or Ringer's acetate with added mannitol. Blood samples were collected before, and 2 and 24 h after cardiopulmonary bypass. Coagulation was assessed by standard coagulation tests and rotational thromboelastometry. Platelet function was assessed with impedance aggregometry. Bleeding volumes and transfusion requirements were recorded. RESULTS: Comparing the groups 2 h after bypass, the dextran group showed lower hemoglobin concentration, hematocrit, platelet count, and fibrinogen concentration, and higher INR and aPTT, as well as longer clot formation time (+41 ± 21 % vs. +8 ± 18 %, p < 0.001) and a larger reduction in fibrinogen-dependent clot strength (-37 ± 12 % vs. -7 ± 20 %, p < 0.001). Adenosine diphosphate-dependent platelet activation was reduced in the dextran group but not in the crystalloid group 2 h after bypass (-14 ± 29 % vs. -1 ± 41 %, p = 0.041). No significant between-group differences in hemostatic variables remained after 24 h, and no significant differences in perioperative bleeding volumes, re-explorations for bleeding, or transfusion rates were observed. CONCLUSIONS: Compared to a crystalloid solution, a dextran-based prime had measurable negative impact on hemostatic variables but no detectable increase in bleeding volume or transfusion requirements in cardiac surgery patients.

Dual or single antiplatelet therapy after coronary surgery for acute coronary syndrome (TACSI trial): Rationale and design of an investigator-initiated, prospective, multinational, registry-based randomized clinical trial.

The TACSI trial (ClinicalTrials.gov Identifier: NCT03560310) tests the hypothesis that 1-year treatment with dual antiplatelet therapy with acetylsalicylic acid (ASA) and ticagrelor is superior to only ASA after isolated coronary artery bypass grafting (CABG) in patients with acute coronary syndrome. The TACSI trial is an investigator-initiated pragmatic, prospective, multinational, multicenter, open-label, registry-based randomized trial with 1:1 randomization to dual antiplatelet therapy with ASA and ticagrelor or ASA only, in patients undergoing first isolated CABG, with a planned enrollment of 2200 patients at Nordic cardiac surgery centers. The primary efficacy end point is a composite of time to all-cause death, myocardial infarction, stroke, or new coronary revascularization within 12 months after randomization. The primary safety end point is time to hospitalization due to major bleeding. Secondary efficacy end points include time to the individual components of the primary end point, cardiovascular death, and rehospitalization due to cardiovascular causes. High-quality health care registries are used to assess primary and secondary end points. The patients will be followed for 10 years. The TACSI trial will give important information useful for guiding the antiplatelet strategy in acute coronary syndrome patients treated with CABG.

Risk factors and treatment of oxygenator high-pressure excursions during cardiopulmonary bypass.

INTRODUCTION: A high-pressure excursion (HPE) is a sudden increase in oxygenator inlet pressure during cardiopulmonary bypass (CPB). The aims of this study were to identify factors associated with HPE, to describe a treatment protocol utilizing epoprostenol in severe cases, and to assess early outcome in HPE patients. METHODS: Patients who underwent cardiac surgery with cardiopulmonary bypass at Sahlgrenska University Hospital 2016-2018 were included in a retrospective observational study. Pre- and post-operative data collected from electronic health records, local databases, and registries were compared between HPE and non-HPE patients. Factors associated with HPE were identified with logistic regression models. RESULTS: In total, 2024 patients were analyzed, and 37 (1.8%) developed HPE. Large body surface area (adjusted Odds Ratio (aOR): 1.43 per 0.1 m2; 95% confidence interval (CI): 1.16-1.76, p < 0.001), higher hematocrit during CPB (aOR: 1.20 per 1%; (1.09-1.33), p < 0.001), acute surgery (aOR: 2.98; (1.26-6.62), p = 0.018), and previous stroke (aOR: 2.93; (1.03-7.20), p = 0.027) were independently associated with HPE. HPE was treated with hemodilution (n = 29, 78.4%), and/or extra heparin (n = 23, 62.2%), and/or epoprostenol (n = 12, 32.4%). No oxygenator change-out was necessary. While there was no significant difference in 30-day mortality (2.7% vs 3.2%, p = 1.0), HPE was associated with a higher perioperative stroke rate (8.1% vs 1.8%, aOR 5.09 (1.17-15.57), p = 0.011). CONCLUSIONS: Large body surface area, high hematocrit during CPB, previous stroke and acute surgery were independently associated with HPE. A treatment protocol including epoprostenol appears to be a safe option. Perioperative stroke rate was increased in HPE patients.

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.

Direct intramyocardial injection of VEGF mRNA in patients undergoing coronary artery bypass grafting.

Vascular endothelial growth factor A (VEGF-A) has therapeutic cardiovascular effects, but delivery challenges have impeded clinical development. We report the first clinical study of naked mRNA encoding VEGF-A (AZD8601) injected into the human heart. EPICCURE (ClinicalTrials.gov: NCT03370887) was a randomized, double-blind study of AZD8601 in patients with left ventricular ejection fraction (LVEF) 30%-50% who were undergoing elective coronary artery bypass surgery. Thirty epicardial injections of AZD8601 (total 3 mg) or placebo in citrate-buffered saline were targeted to ischemic but viable myocardial regions mapped using quantitative [15O]-water positron emission tomography. Seven patients received AZD8601 and four received placebo and were followed for 6 months. There were no deaths or treatment-related serious adverse events and no AZD8601-associated infections, immune reactions, or arrhythmias. Exploratory outcomes indicated potential improvement in LVEF, Kansas City Cardiomyopathy Questionnaire scores, and N-terminal pro-B-type natriuretic peptide levels, but the study is limited in size, and significant efficacy conclusions are not possible from the dataset. Naked mRNA without lipid encapsulation may provide a safe delivery platform for introducing genetic material to cardiac muscle, but further studies are needed to confirm efficacy and safety in a larger patient pool.

Long-term antithrombotic therapy after coronary artery bypass grafting in patients with preoperative atrial fibrillation. A nationwide observational study from the SWEDEHEART registry.

AIMS: To provide data guiding long-term antithrombotic therapy after coronary artery by-pass grafting (CABG) in patients with preoperative atrial fibrillation (AF). METHODS AND RESULTS: From the SWEDEHEART registry, we included all patients, between January 2006 and September 2016, with preoperative AF and CHA2DS2-VASC score ≥2, undergoing CABG. Based on dispensed prescriptions 12 to 18 months after CABG, patients were divided in 3 groups: use of platelet inhibitors (PI) only, oral anticoagulant (OAC) only or a combination of OAC + PI. Outcomes were: Major adverse cardiac and cerebrovascular events (MACCE, [all-cause death, myocardial infarction, or stroke]), net adverse clinical events (NACE, [MACCE or bleeding]) and the individual components of NACE. Inverse probability of treatment weighting was used to adjust for the non-randomized study design. Among 2,564 patients, 1,040 (41%) were treated with PI alone, 1,064 (41%) with OAC alone, and 460 (18%) with PI + OAC. Treatment with PI alone was associated with higher risk for MACCE (adjusted HR 1.43, 95% CI 1.09-1.88), driven by higher risk for stroke and MI, compared with OAC alone. Treatment with PI + OAC, was associated with higher risk for NACE (adjusted HR 1.40, 95% CI 1.06-1.85), driven by higher risk for bleeds, compared with OAC alone. CONCLUSION: In this real-world observational study, a high proportion of patients with AF, undergoing CABG, did not receive a long-term OAC therapy. Treatment with OAC alone was associated with a net clinical benefit, compared with PI alone or PI + OAC.