Fibrosis and expression of extracellular matrix proteins in human interventricular septum in aortic valve stenosis and regurgitation.

Valvular heart disease leads to ventricular pressure and/or volume overload. Pressure overload leads to fibrosis, which might regress with its resolution, but the limits and details of this reverse remodeling are not known. To gain more insight into the extent and nature of cardiac fibrosis in valve disease, we analyzed needle biopsies taken from the interventricular septum of patients undergoing surgery for valve replacement focusing on the expression and distribution of major extracellular matrix protein involved in this process. Proteomic analysis performed using mass spectrometry revealed an excellent correlation between the expression of collagen type I and III, but there was little correlation with the immunohistochemical staining performed on sister sections, which included antibodies against collagen I, III, fibronectin, sarcomeric actin, and histochemistry for wheat germ agglutinin. Surprisingly, the immunofluorescence intensity did not correlate significantly with the gold standard for fibrosis quantification, which was performed using Picrosirius Red (PSR) staining, unless multiplexed on the same tissue section. There was also little correlation between the immunohistochemical markers and pressure gradient severity. It appears that at least in humans, the immunohistochemical pattern of fibrosis is not clearly correlated with standard Picrosirius Red staining on sister sections or quantitative proteomic data, possibly due to tissue heterogeneity at microscale, comorbidities, or other patient-specific factors. For precise correlation of different types of staining, multiplexing on the same section is the best approach.

Sequential hybrid ablation vs. surgical CryoMaze alone for treatment of atrial fibrillation: results of multicentre randomized controlled trial.

AIMS: Data on the hybrid atrial fibrillation (AF) treatment are lacking in patients with structural heart disease undergoing concomitant CryoMaze procedures. The aim was to assess whether the timely pre-emptive catheter ablation would achieve higher freedom from AF or atrial tachycardia (AT) and be associated with better clinical outcomes than surgical ablation alone. METHODS AND RESULTS: The trial investigated patients with non-paroxysmal AF undergoing coronary artery bypass grafting and/or valve repair/replacement with mandatory concomitant CryoMaze procedure who were randomly assigned to undergo either radiofrequency catheter ablation [Hybrid Group (HG)] or no further treatment (Surgery Group). The primary efficacy endpoint was the first recurrence of AF/AT without class I or III antiarrhythmic drugs as assessed by implantable cardiac monitors. The primary clinical endpoint was a composite of hospitalization for arrhythmia recurrence, worsening of heart failure, cardioembolic event, or major bleeding. We analysed 113 and 116 patients in the Hybrid and Surgery Groups, respectively, with a median follow-up of 715 (IQR: 528-1072) days. The primary efficacy endpoint was significantly reduced in the HG [41.1% vs. 67.4%, hazard ratio (HR) = 0.38, 95% confidence interval (CI): 0.26-0.57, P < 0.001] as well as the primary clinical endpoint (19.9% vs. 40.1%, HR = 0.51, 95% CI: 0.29-0.86, P = 0.012). The trial groups did not differ in all-cause mortality (10.6% vs. 8.6%, HR = 1.17, 95%CI: 0.51-2.71, P = 0.71). The major complications of catheter ablation were infrequent (1.9%). CONCLUSION: Pre-emptively performed catheter ablation after the CryoMaze procedure was safe and associated with higher freedom from AF/AT and improved clinical outcomes.

Femoral arterial cannulation for surgical repair of stanford type A aortic dissection.

BACKGROUND: The benefits and harms associated with femoral artery cannulation over other sites of arterial cannulation for surgical repair of acute Stanford type A aortic dissection (TAAD) are not conclusively established. METHODS: We evaluated the outcomes after surgery for TAAD using femoral artery cannulation, supra-aortic arterial cannulation (i.e., innominate/subclavian/axillary artery cannulation), and direct aortic cannulation. RESULTS: 3751 (96.1%) patients were eligible for this analysis. In-hospital mortality using supra-aortic arterial cannulation was comparable to femoral artery cannulation (17.8% vs. 18.4%; adjusted OR 0.846, 95% CI 0.799-1.202). This finding was confirmed in 1028 propensity score-matched pairs of patients with supra-aortic arterial cannulation or femoral artery cannulation (17.5% vs. 17.0%, p = 0.770). In-hospital mortality after direct aortic cannulation was lower compared to femoral artery cannulation (14.0% vs. 18.4%, adjusted OR 0.703, 95% CI 0.529-0.934). Among 583 propensity score-matched pairs of patients, direct aortic cannulation was associated with lower rates of in-hospital mortality (13.4% vs. 19.6%, p = 0.004) compared to femoral artery cannulation. Switching of the primary site of arterial cannulation was associated with increased rate of in-hospital mortality (36.5% vs. 17.0%; adjusted OR 2.730, 95% CI 1.564-4.765). Ten-year mortality was similar in the study cohorts. CONCLUSIONS: In this study, the outcomes of surgery for TAAD using femoral arterial cannulation were comparable to those using supra-aortic arterial cannulation. However, femoral arterial cannulation was associated with higher in-hospital mortality than direct aortic cannulation. TRIAL REGISTRATION: ClinicalTrials.gov registration code: NCT04831073.

Current Outcome after Surgery for Type A Aortic Dissection.

OBJECTIVE: The aim of this study was to evaluate the outcomes of different surgical strategies for acute Stanford type A aortic dissection (TAAD). SUMMARY BACKGROUND DATA: The optimal extent of aortic resection during surgery for acute TAAD is controversial. METHODS: This is a multicenter, retrospective cohort study of patients who underwent surgery for acute TAAD at 18 European hospitals. RESULTS: Out of 3902 consecutive patients, 689 (17.7%) died during the index hospitalization. Among 2855 patients who survived 3 months after surgery, 10-year observed survival was 65.3%, while country-adjusted, age-adjusted, and sex-adjusted expected survival was 81.3%, yielding a relative survival of 80.4%. Among 558 propensity score-matched pairs, total aortic arch replacement increased the risk of in-hospital (21.0% vs. 14.9%, P =0.008) and 10-year mortality (47.1% vs. 40.1%, P =0.001), without decreasing the incidence of distal aortic reoperation (10-year: 8.9% vs. 7.4%, P =0.690) compared with ascending aortic replacement. Among 933 propensity score-matched pairs, in-hospital mortality (18.5% vs. 18.0%, P =0.765), late mortality (at 10-year: 44.6% vs. 41.9%, P =0.824), and cumulative incidence of proximal aortic reoperation (at 10-year: 4.4% vs. 5.9%, P =0.190) after aortic root replacement was comparable to supracoronary aortic replacement. CONCLUSIONS: Replacement of the aortic root and aortic arch did not decrease the risk of aortic reoperation in patients with TAAD and should be performed only in the presence of local aortic injury or aneurysm. The relative survival of TAAD patients is poor and suggests that the causes underlying aortic dissection may also impact late mortality despite surgical repair of the dissected aorta.

Changes in cognitive function after thoracoscopic and catheter ablation for atrial fibrillation.

BACKGROUND: Comparative data regarding the effect of percutaneous and thoracoscopic ablation of atrial fibrillation (AF) on cognitive function are very limited. The aim of the study was to determine and compare the effect of both types of ablations on patient cognitive functions in the mid-term. METHODS: Patients with AF indicated for ablation procedure were included. Forty-six patients underwent thoracoscopic, off-pump ablation using the COBRA Fusion radiofrequency system, followed by a catheter ablation three months afterward (Hybrid group). A comparative cohort of 53 AF patients underwent pulmonary vein isolation only (PVI group). Neuropsychological examinations were done before and nine months after the surgical or catheter ablation procedure. Neuropsychological testing comprised 13 subtests of seven domains, and the results were expressed as post-operative cognitive dysfunction (POCD) nine months after the procedure. RESULTS: Patients in both groups were similar with respect to the baseline clinical characteristics; only non-paroxysmal AF was more common in the hybrid group (98% vs. 34%). Major POCD was present in eight (17.4%) of hybrid patients versus three (5.7%) of PVI patients (p = 0.11), combined (major/minor) worsened cognitive decline was present in 10 (21.7%) hybrid patients versus three (5.6%) PVI patients (p = 0.034). On the other hand, combined (major/minor) improvement was present in 15 (32.6%) hybrid patients versus nine (16.9%) patients in the PVI group (p = 0.099). CONCLUSION: Hybrid ablation, a combination of thoracoscopic and percutaneous ablation, is associated with a higher risk of cognitive decline compared to sole percutaneous ablation.

Direct Aortic Versus Supra-Aortic Arterial Cannulation During Surgery for Acute Type A Aortic Dissection.

AIMS: In this study we evaluated the impact of direct aortic cannulation versus innominate/subclavian/axillary artery cannulation on the outcome after surgery for type A aortic dissection. METHODS: The outcomes of patients included in a multicenter European registry (ERTAAD) who underwent surgery for acute type A aortic dissection with direct aortic cannulation versus those with innominate/subclavian/axillary artery cannulation, i.e. supra-aortic arterial cannulation, were compared using propensity score matched analysis. RESULTS: Out of 3902 consecutive patients included in the registry, 2478 (63.5%) patients were eligible for this analysis. Direct aortic cannulation was performed in 627 (25.3%) patients, while supra-aortic arterial cannulation in 1851 (74.7%) patients. Propensity score matching yielded 614 pairs of patients. Among them, patients who underwent surgery for TAAD with direct aortic cannulation had significantly decreased in-hospital mortality (12.7% vs. 18.1%, p = 0.009) compared to those who had supra-aortic arterial cannulation. Furthermore, direct aortic cannulation was associated with decreased postoperative rates of paraparesis/paraplegia (2.0 vs. 6.0%, p < 0.0001), mesenteric ischemia (1.8 vs. 5.1%, p = 0.002), sepsis (7.0 vs. 14.2%, p < 0.0001), heart failure (11.2 vs. 15.2%, p = 0.043), and major lower limb amputation (0 vs. 1.0%, p = 0.031). Direct aortic cannulation showed a trend toward decreased risk of postoperative dialysis (10.1 vs. 13.7%, p = 0.051). CONCLUSIONS: This multicenter cohort study showed that direct aortic cannulation compared to supra-aortic arterial cannulation is associated with a significant reduction of the risk of in-hospital mortality after surgery for acute type A aortic dissection. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04831073.

Sequential hybrid ablation versus surgical CryoMaze alone for treatment of atrial fibrillation (SurHyb Trial): a protocol of the multicentre randomized controlled trial.

BACKGROUND: Atrial fibrillation is common in patients with structural heart disease who are undergoing cardiac surgery. Surgical CryoMaze has been shown to be an effective treatment in several trials, but success rates have varied considerably, between 47-95%. The sequential hybrid approach, combining surgical CryoMaze followed by radiofrequency catheter ablation, can achieve high freedom from atrial arrhythmias. However, in patients with concomitant surgical atrial fibrillation treatment, data comparing the hybrid approach to CryoMaze alone are lacking. METHODS: The SurHyb study was designed as a prospective, open-label, multicentre randomized trial. Patients with non-paroxysmal atrial fibrillation who were scheduled for coronary artery bypass grafting or valve repair/replacement were randomized to either surgical CryoMaze alone or surgical CryoMaze followed by radiofrequency catheter ablation 3 months post-surgery. The primary outcome measure was arrhythmia-free survival without class I or III antiarrhythmic drugs, which has been evaluated using implantable cardiac monitors. CONCLUSIONS: This is the first randomized study that compares concomitant surgical CryoMaze alone with the staged hybrid surgical CryoMaze followed by catheter ablation, in patients with non-paroxysmal atrial fibrillation using rigorous rhythm monitoring. The results may contribute to the optimization of the treatment in patients undergoing concomitant CryoMaze for atrial fibrillation.

Trans-generational neurochemical modulation of methamphetamine in the adult brain of the Wistar rat.

Chronic methamphetamine (METH) abuse has been shown to elicit strong neurotoxic effects. Yet, with an increasing number of children born to METH abusing mothers maturing into adulthood, one important question is how far do the neurotoxic effects of METH alter various neurotransmitter systems in the adult METH-exposed offspring. The purpose of this study was to investigate long-term trans-generational neurochemical changes, following prenatal METH exposure, in the adult Wistar rat brain. METH or saline (SAL-control animals) was administered to pregnant dams throughout the entire gestation period (G0-G22). At postnatal day 90, dopamine, serotonin, glutamate and GABA were measured in the adult brain before (baseline) and after a METH re-administration using in vivo microdialysis and liquid chromatography/mass spectrometry. The results show that METH-exposure increased basal levels of monoamines and glutamate, but decreased GABA levels in all measured brain regions. Acute challenge with METH injection in the METH-exposed group induced a lower increase in the monoamine system relative to the increase in the GABAergic and glutamatergic system. The data show that prenatal METH exposure has strong effects on the monoaminergic, GABAergic and glutamatergic system even when exposure to METH was limited to the prenatal phase. Toxicological effects of METH have therefore longer lasting effects as currently considered and seem to affect the excitatory-inhibitory balance in the brain having strong implications for cognitive and behavioral functioning.

Native T1 Relaxation Time and Extracellular Volume Fraction as Accurate Markers of Diffuse Myocardial Fibrosis in Heart Valve Disease　- Comparison With Targeted Left Ventricular Myocardial Biopsy.

BACKGROUND: The aim of our study was to investigate the relationship between the cardiac magnetic resonance (CMR)-derived native T1 relaxation time and myocardial extracellular volume (ECV) fraction and the extent of diffuse myocardial fibrosis (DMF) on targeted myocardial left ventricular (LV) biopsy. METHODS AND RESULTS: The study population consisted of 40 patients (age 63±8 years, 65% male) undergoing valve and/or ascending aorta surgery for severe aortic stenosis (77.5%), root dilatation (7.5%) or valve regurgitation (15%). The T1 relaxation time was assessed in the basal interventricular septum pre- and 10-min post-contrast administration using the modified Look-Locker Inversion recovery sequence prior to surgery. LV myocardial biopsy specimen was obtained during surgery from the basal interventricular septal segment matched with the T1 mapping assessment. The percentage of myocardial collagen was quantified using picrosirius red staining. The average percentage of myocardial collagen was 22.0±14.8%. Both native T1 relaxation time with cutoff value ≥1,010 ms (sensitivity=90%, specificity=73%, area under the curve=0.82) and ECV with cutoff value ≥0.32 (sensitivity=80%, specificity=90%, area under the curve=0.85) showed high accuracy to identify severe (>30%) DMF. The native T1 relaxation time showed significant correlation with LV mass (P<0.01). CONCLUSIONS: Native T1 relaxation time and ECV at 10 min after contrast administration are accurate markers of DMF. (Circ J 2016; 80: 1202-1209).

Markers of nucleic acids and proteins oxidation among office workers exposed to air pollutants including (nano)TiO2 particles.

OBJECTIVES: Experimental studies using nanoscale TiO2 have documented lung injury, inflammation, oxidative stress, and genotoxicity. Human health data are extremely scarce. METHODS: In exhaled breath condensate (EBC) and urine of 22 office employees occupationally exposed to TiO2 during their visit in the production workshops for average 14±9 min/day a panel of biomarkers of nucleic acids and proteins oxidation was studied, specifically 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-OHG), 5-hydroxymethyl uracil (5-OHMeU), o-tyrosine (o-Tyr), 3-chlorotyrosine (3-ClTyr), and 3-nitrotyrosine (3-NOTyr). Examination was performed also in 14 comparable controls. RESULTS: The median respirable TiO2 mass concentration in the workshops was 0.40 mg/m3, median number concentration was 2.32×104 particles/cm3 with 80% of the particles being <100 nm in diameter. All 6 markers of oxidation were elevated in EBC in factory office employees relative to controls (p<0.01). Significant association was found between their job in TiO2 production plant and 5 markers of oxidation (except 3-NOTyr) in the EBC in multivariate analysis. No elevation of markers was detected in the urine. CONCLUSION: This pilot study suggests that even short nanoTiO2 exposure may lead to pulmonary oxidative stress; however this effect may be short-term and reversible. The clinical significance of these findings is unclear and more studies are needed.

Experimental and theoretical perspectives of the Noyori-Ikariya asymmetric transfer hydrogenation of imines.

The asymmetric transfer hydrogenation (ATH) of imines catalyzed by the Noyori-Ikariya [RuCl(η6-arene)(N-arylsulfonyl-DPEN)] (DPEN=1,2-diphenylethylene-1,2-diamine) half-sandwich complexes is a research topic that is still being intensively developed. This article focuses on selected aspects of this catalytic system. First, a great deal of attention is devoted to the N-arylsulfonyl moiety of the catalysts in terms of its interaction with protonated imines (substrates) and amines (components of the hydrogen-donor mixture). The second part is oriented toward the role of the η6-coordinated arene. The final part concerns the imine substrate structural modifications and their importance in connection with ATH. Throughout the text, the summary of known findings is complemented with newly-presented ones, which have been approached both experimentally and computationally.

Lesion durability found during mandated percutaneous catheter ablation after surgical cryo-ablation for treatment of non-paroxysmal atrial fibrillation.

OBJECTIVES: Current recommendations support surgical treatment of atrial fibrillation (AF) in patients indicated for cardiac surgery. These procedures are referred to as concomitant and may be carried out using radiofrequency energy or cryo-ablation. This study aimed to assess the electrophysiological findings in patients undergoing concomitant cryo-ablation. METHODS: Patients with non-paroxysmal AF undergoing coronary artery bypass grafting and/or valve repair/replacement were included in the trial if concomitant cryo-ablation was part of the treatment plan according to current guidelines. The patients reported in this study were assigned to undergo staged percutaneous radiofrequency catheter ablation (PRFCA), i.e., hybrid treatment, as a part of the SURHYB trial protocol. RESULTS: We analyzed 103 patients who underwent PRFCA 105 ± 35 days after surgery. Left and right pulmonary veins (PVs) were found isolated in 65 (63.1%) and 63 (61.2%) patients, respectively. The LA posterior wall isolation and mitral isthmus conduction block were found in 38 (36.9%) and 18 (20.0%) patients, respectively. Electrical reconnections (gaps) in the left PVs were more often localized superiorly than inferiorly (57.9% vs. 26.3%, P = 0.005) and anteriorly than posteriorly (65.8% vs. 31.6%, P = 0.003). Gaps in the right PVs were more equally distributed anteroposteriorly but dominated in superior segments (72.5% vs. 40.0%, P = 0.003). There was a higher number of gaps on the roof line compared to the inferior line (131 (67.2%) vs. 67 (42.2%), P < 0.001). Compared to epicardial cryo-ablation, endocardial was more effective in creating PVs and LA posterior wall isolation (P < 0.05). Cryo-ablation using nitrous oxide (N20) or argon (Ar) gas as cooling agents was similarly effective (P = NS). CONCLUSIONS: The effectiveness of surgical cryo-ablation in achieving transmural and durable lesions in the left atrium is surprisingly low. Gaps are located predominantly in the superior and anterior portions of the PVs and on the roof line. Endocardial cryo-ablation is more effective than epicardial ablation, irrespective of the cooling agent used.

Role of gender in short- and long-term outcomes after surgery for type A aortic dissection: analysis of a multicentre European registry.

OBJECTIVES: Gender difference in the outcome after type A aortic dissection (TAAD) surgery remains an issue of ongoing debate. In this study, we aimed to evaluate the impact of gender on the short- and long-term outcome after surgery for TAAD. METHODS: A multicentre European registry retrospectively included all consecutive TAAD surgery patients between 2005 and 2021 from 18 hospitals across 8 European countries. Early and late mortality, and cumulative incidence of aortic reoperation were compared between genders. RESULTS: A total of 3902 patients underwent TAAD surgery, with 1185 (30.4%) being females. After propensity score matching, 766 pairs of males and females were compared. No statistical differences were detected in the early postoperative outcome between genders. Ten-year survival was comparable between genders (47.8% vs 47.1%; log-rank test, P = 0.679), as well as cumulative incidences of distal or proximal aortic reoperations. Ten-year relative survival compared to country-, year-, age- and sex-matched general population was higher among males (0.65) compared to females (0.58). The time-period subanalysis revealed advancements in surgical techniques in both genders over the years. However, an increase in stroke was observed over time for both populations, particularly among females. CONCLUSIONS: The past 16 years have witnessed marked advancements in surgical techniques for TAAD in both males and females, achieving comparable early and late mortality rates. Despite these findings, late relative survival was still in favour of males.

Classification of the Urgency of the Procedure and Outcome of Acute Type A Aortic Dissection.

Surgery for type A aortic dissection (TAAD) is associated with a high risk of early mortality. The prognostic impact of a new classification of the urgency of the procedure was evaluated in this multicenter cohort study. Data on consecutive patients who underwent surgery for acute TAAD were retrospectively collected in the multicenter, retrospective European Registry of TAAD (ERTAAD). The rates of in-hospital mortality of 3,902 consecutive patients increased along with the ERTAAD procedure urgency grades: urgent procedure 10.0%, emergency procedure grade 1 13.3%, emergency procedure grade 2 22.1%, salvage procedure grade 1 45.6%, and salvage procedure grade 2 57.1% (p <0.0001). Preoperative arterial lactate correlated with the urgency grades. Inclusion of the ERTAAD procedure urgency classification significantly improved the area under the receiver operating characteristics curves of the regression model and the integrated discrimination indexes and the net reclassification indexes. The risk of postoperative stroke/global brain ischemia, mesenteric ischemia, lower limb ischemia, dialysis, and acute heart failure increased along with the urgency grades. In conclusion, the urgency of surgical repair of acute TAAD, which seems to have a significant impact on the risk of in-hospital mortality, may be useful to improve the stratification of the operative risk of these critically ill patients. This study showed that salvage surgery for TAAD is justified because half of the patients may survive to discharge.

Nature of Neurological Complications and Outcome After Surgery for Type A Aortic Dissection.

Surgery for type A aortic dissection (TAAD) is frequently complicated by neurologic complications. The prognostic impact of neurologic complications of different nature has been investigated in this study. The subjects of this analysis were 3,902 patients who underwent surgery for acute TAAD from the multicenter European Registry of Type A Aortic Dissection (ERTAAD). During the index hospitalization, 722 patients (18.5%) experienced stroke/global brain ischemia. Ischemic stroke was detected in 539 patients (13.8%), hemorrhagic stroke in 76 patients (1.9%) and global brain ischemia in 177 patients (4.5%), with a few patients having had findings of more than 1 of these conditions. In-hospital mortality was increased significantly in patients with postoperative ischemic stroke (25.6%, adjusted odds ratio [OR] 2.422, 95% confidence interval [CI] 1.825 to 3.216), hemorrhagic stroke (48.7%, adjusted OR 4.641, 95% CI 2.524 to 8.533), and global brain ischemia (74.0%, adjusted OR 22.275, 95% CI 14.537 to 35.524) compared with patients without neurologic complications (13.5%). Similarly, patients who experienced ischemic stroke (46.3%, adjusted hazard ratio [HR] 1.719, 95% CI 1.434 to 2.059), hemorrhagic stroke (62.8%, adjusted HR 3.236, 95% CI 2.314 to 4.525), and global brain ischemia (83.9%, adjusted HR 12.777, 95% CI 10.325 to 15.810) had significantly higher 5-year mortality than patients without postoperative neurologic complications (27.5%). The negative prognostic effect of neurologic complications on survival vanished about 1 year after surgery. In conclusion, postoperative ischemic stroke, hemorrhagic stroke, and global cerebral ischemia increased early and midterm mortality after surgery for acute TAAD. The magnitude of risk of mortality increased with the severity of the neurologic complications, with postoperative hemorrhagic stroke and global brain ischemia being highly lethal complications.

Practical aspects and mechanism of asymmetric hydrogenation with chiral half-sandwich complexes.

This review is oriented toward the asymmetric transfer hydrogenation (ATH) of imines regarding mostly fundamental, yet important topics from the practical point of view. Development of analytical methods for the monitoring of ATH (i.e., kinetics and stereoselectivity) belongs to those topics, as well as studies on the influence of reaction conditions and structural variations on the reaction performance. The second part is devoted to the reaction mechanism with the emphasis on imine ATH and catalyst behaviour under acidic conditions. The review also addresses the asymmetric hydrogenation (AH) of ketones and imines using molecular hydrogen and the application of ATH in pharmaceutical projects. The contributions of our group to each area are included.

A bromine analogue of picoplatin: a new substance from the group of platinum-based chemotherapeutics.

A new substance, cis-amminedibromido(2-methylpyridine-κN)platinum(II), cis-[PtBr2(C6H7N)(NH3)], which is a potential platinum-based antineoplastic agent for the treatment of patients with solid tumors, has been synthesized and structurally characterized. There is one molecule in the asymmetric unit and molecules are linked via two symmetry-independent N-H···Br hydrogen bonds into zigzag chains running parallel to the c axis. C-H···Br hydrogen bonds crosslink these chains to give a layer parallel to (010). N-H···Br hydrogen bonds and π-π stacking interactions between pairs of pyridine rings stack the layers along b.

Interinstitutional analysis of the outcome after surgery for type A aortic dissection.

PURPOSE: To evaluate the impact of individual institutions on the outcome after surgery for Stanford type A aortic dissection (TAAD). METHODS: This is an observational, multicenter, retrospective cohort study including 3902 patients who underwent surgery for TAAD at 18 university and non-university hospitals. RESULTS: Logistic regression showed that four hospitals had increased risk of in-hospital mortality, while two hospitals were associated with decreased risk of in-hospital mortality. Risk-adjusted in-hospital mortality rates were lower in four hospitals and higher in other four hospitals compared to the overall in-hospital mortality rate (17.7%). Participating hospitals were classified as overperforming or underperforming if their risk-adjusted in-hospital mortality rate was lower or higher than the in-hospital mortality rate of the overall series, respectively. Propensity score matching yielded 1729 pairs of patients operated at over- or underperforming hospitals. Overperforming hospitals had a significantly lower in-hospital mortality (12.8% vs. 22.2%, p < 0.0001) along with decreased rate of stroke and/or global brain ischemia (16.5% vs. 19.9%, p = 0.009) compared to underperforming hospitals. Aggregate data meta-regression of the results of participating hospitals showed that hospital volume was inversely associated with in-hospital mortality (p = 0.043). Hospitals with an annual volume of less than 15 cases had an increased risk of in-hospital mortality (adjusted OR, 1.345, 95% CI 1.126-1.607). CONCLUSION: The present findings indicate that there are significant differences between hospitals in terms of early outcome after surgery for TAAD. Low hospital volume may be a determinant of poor outcome of TAAD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04831073.

Preoperative arterial lactate and outcome after surgery for type A aortic dissection: The ERTAAD multicenter study.

Background: Acute type A aortic dissection (TAAD) is associated with significant mortality and morbidity. In this study we evaluated the prognostic significance of preoperative arterial lactate concentration on the outcome after surgery for TAAD. Methods: The ERTAAD registry included consecutive patients who underwent surgery for acute type A aortic dissection (TAAD) at 18 European centers of cardiac surgery. Results: Data on arterial lactate concentration immediately before surgery were available in 2798 (71.7 %) patients. Preoperative concentration of arterial lactate was an independent predictor of in-hospital mortality (mean, 3.5 ± 3.2 vs 2.1 ± 1.8 mmol/L, adjusted OR 1.181, 95%CI 1.129-1.235). The best cutoff value preoperative arterial lactate concentration was 1.8 mmol/L (in-hospital mortality, 12.0 %, vs. 26.6 %, p < 0.0001). The rates of in-hospital mortality increased along increasing quintiles of arterial lactate and it was 12.1 % in the lowest quintile and 33.6 % in the highest quintile (p < 0.0001). The difference between multivariable models with and without preoperative arterial lactate was statistically significant (p = 0.0002). The NRI was 0.296 (95%CI 0.200-0.391) (p < 0.0001) with -17 % of events correctly reclassified (p = 0.0002) and 46 % of non-events correctly reclassified (p < 0.0001). The IDI was 0.025 (95%CI 0.016-0.034) (p < 0.0001). Six studies from a systematic review plus the present one provided data for a pooled analysis which showed that the mean difference of preoperative arterial lactate between 30-day/in-hospital deaths and survivors was 1.85 mmol/L (95%CI 1.22-2.47, p < 0.0001, I2 64 %). Conclusions: Hyperlactatemia significantly increased the risk of mortality after surgery for acute TAAD and should be considered in the clinical assessment of these critically ill patients.

Baseline risk factors of in-hospital mortality after surgery for acute type A aortic dissection: an ERTAAD study.

Background: Surgery for type A aortic dissection (TAAD) is associated with high risk of mortality. Current risk scoring methods have a limited predictive accuracy. Methods: Subjects were patients who underwent surgery for acute TAAD at 18 European centers of cardiac surgery from the European Registry of Type A Aortic Dissection (ERTAAD). Results: Out of 3,902 patients included in the ERTAAD, 2,477 fulfilled the inclusion criteria. In the validation dataset (2,229 patients), the rate of in-hospital mortality was 18.4%. The rate of composite outcome (in-hospital death, stroke/global ischemia, dialysis, and/or acute heart failure) was 41.2%, and 10-year mortality rate was 47.0%. Logistic regression identified the following patient-related variables associated with an increased risk of in-hospital mortality [area under the curve (AUC), 0.755, 95% confidence interval (CI), 0.729-0.780; Brier score 0.128]: age; estimated glomerular filtration rate; arterial lactate; iatrogenic dissection; left ventricular ejection fraction ≤50%; invasive mechanical ventilation; cardiopulmonary resuscitation immediately before surgery; and cerebral, mesenteric, and peripheral malperfusion. The estimated risk score was associated with an increased risk of composite outcome (AUC, 0.689, 95% CI, 0.667-0.711) and of late mortality [hazard ratio (HR), 1.035, 95% CI, 1.031-1.038; Harrell's C 0.702; Somer's D 0.403]. In the validation dataset (248 patients), the in-hospital mortality rate was 16.1%, the composite outcome rate was 41.5%, and the 10-year mortality rate was 49.1%. The estimated risk score was predictive of in-hospital mortality (AUC, 0.703, 95% CI, 0.613-0.793; Brier score 0.121; slope 0.905) and of composite outcome (AUC, 0.682, 95% CI, 0.614-0.749). The estimated risk score was predictive of late mortality (HR, 1.035, 95% CI, 1.031-1.038; Harrell's C 0.702; Somer's D 0.403), also when hospital deaths were excluded from the analysis (HR, 1.024, 95% CI, 1.018-1.031; Harrell's C 0.630; Somer's D 0.261). Conclusions: The present analysis identified several baseline clinical risk factors, along with preoperative estimated glomerular filtration rate and arterial lactate, which are predictive of in-hospital mortality and major postoperative adverse events after surgical repair of acute TAAD. These risk factors may be valuable components for risk adjustment in the evaluation of surgical and anesthesiological strategies aiming to improve the results of surgery for TAAD. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT04831073.