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Objectives: Paraplegia is devastating complication associated with thoracic and thoracoabdominal aortic aneurysm repair. Vast evidence has been gathered on pre-, peri- and postoperative protective adjuncts aiming to minimize spinal cord ischemia. This review focuses on the pretreatment phase of open surgical or endovascular aortic procedures and gathers the experimental data on the interventional preconditioning and priming methods that increase the spinal cord ischemic tolerance. Design: By the start of March 2021, a systematic review was performed in PubMed, Scopus and Web of Science core collection to identify the articles that reported (i) either an ischemic preconditioning, remote ischemic preconditioning or priming method prior to (ii) experimental spinal cord ischemia performed in endovascular or open surgical fashion mimicking either thoracic, abdominal or thoracoabdominal aortic aneurysm procedures. (iii) The outcomes were reported via neurological, motor-evoked potential, somatosensory-evoked potential, histopathological, immunohistochemical, physiological analysis, or in different combinations of these measurements. Results: The search yielded 7802 articles, and 57 articles were included in the systematic review. The articles were assessed by the evaluated species, the utilized pretreatment, the measured protective effects, and the suggested underlying mechanisms. Conclusions: The reviewed articles showed several possible mechanisms in ischemic and remote ischemic preconditioning for prevention of spinal cord ischemia. The main suggested method for priming was arteriogenetic stimulus. Future studies should confirm these hints of arteriogenetic stimulus with more precise quantification of the protective recruitment process.

Background: Acute type B aortic dissection (TBAD) is a severe condition associated with significant morbidity and mortality. The optimal classification and treatment strategy of TBAD remain controversial and inconsistent. Methods: This analysis includes patients treated for acute TBAD at the Helsinki University Hospital, Finland between 2007 and 2019. The endpoints were early and late mortality, intervention of the aorta, and a composite of death and aortic intervention in uncomplicated patients and high-risk patients. Results: This study included 162 consecutive TBAD patients (27.8% females), 114 in the high-risk group and 48 in the uncomplicated group, with a mean age of 67.6 ± 13.9 years. Intramural hematoma was reported in 63 cases (38.9%). The mean follow-up was 5.1 ± 3.9 years. In-hospital/30-day mortality (n = 4; 3.5%) occurred solely in the high-risk group (P = 0.32). Additionally, TBAD-related adverse events (n = 23; 20.2%) were observed only in the high-risk group (P < 0.001). The cumulative incidences of the composite TBAD outcome with non–TBAD-related death as a competing risk were 6.6% (95% CI, 1.7%–16.5%) in the uncomplicated group and 29.5% (95% CI, 21.1%–38.3%) in the high-risk group at 5 years and 6.6% (95% CI, 1.7%–16.5%) and 33.0% (95% CI, 23.7%–42.6%) at 10 years (P = 0.001, Gray test). Extracardiac arteriopathy (subdistribution hazard ratio [SHR], 2.61; 95% CI, 1.08–6.27) and coronary artery disease (SHR, 2.24; 95% CI, 1.07–4.71) were risk factors for adverse aortic-related events in univariable competing-risk regression analysis. Conclusions: Recognition of risk factors underlying adverse events related to TBAD is essential because the disease progression impacts both early and late outcomes. Early aortic repair in high-risk TBAD may reduce long-term morbidity and mortality.

Objectives: Less-invasive and continuous cardiac output monitors recently have been developed to monitor patient hemodynamics. The aim of this study was to compare the accuracy, precision, and trending ability of noninvasive bioreactance-based Starling SV and miniinvasive pulse-power device LiDCOrapid to bolus thermodilution technique with a pulmonary artery catheter (TDCO) when measuring cardiac index in the setting of cardiac surgery with cardiopulmonary bypass (CPB). Design: A prospective method-comparison study. Setting: Oulu University Hospital, Finland. Participants: Twenty patients undergoing cardiac surgery with CPB. Interventions: Cardiac index measurements were obtained simultaneously with TDCO intraoperatively and postoperatively, resulting in 498 measurements with Starling SV and 444 with LiDCOrapid. Measurements and Main Results: The authors used the Bland-Altman method to investigate the agreement between the devices and four-quadrant plots with error grids to assess the trending ability. The agreement between TDCO and Starling SV was qualified with a bias of 0.43 L/min/m² (95% confidence interval [CI], 0.37‐0.50), wide limits of agreement (LOA, –1.07 to 1.94 L/min/m²), and a percentage error (PE) of 66.3%. The agreement between TDCO and LiDCOrapid was qualified, with a bias of 0.22 L/min/m² (95% CI 0.16‐0.27), wide LOA (–0.93 to 1.43), and a PE of 53.2%. With both devices, trending ability was insufficient. Conclusions: The reliability of bioreactance-based Starling SV and pulse-power analyzer LiDCOrapid was not interchangeable with TDCO, thus limiting their usefulness in cardiac surgery with CPB.

Objectives: Since selective cerebral perfusion (SCP) has been used in aortic arch surgical procedures, the core temperature during lower body circulatory arrest (LBCA) has been steadily rising. Simultaneously, the use of a frozen elephant trunk (FET) graft has been increasing. The safe period of LBCA in relation to spinal cord ischaemic tolerance in combination with segmental artery occlusion by the FET procedure has not been defined. Methods: Sixteen pigs were assigned to undergo 65 (n = 10) or 90 min (n = 6) of SCP at 28°C with LBCA in combination with occlusion of the 8 uppermost segmental arteries in the thoracic (Th) aorta (15–20 cm FET, Th8-level). The follow-up period consisted of a 6-h intensive period and a 5-day observation period. Near-infrared spectroscopy of the collateral network was used to determine spinal cord oxygenation. The neurological status of the patients was evaluated daily, and the brain and the spinal cord were harvested for a histopathological analysis. Results: Five out of 6 pigs after 90 min and 1 out of 10 pigs after 65 min of LBCA died within 48 h of multiorgan failure. Of the survivors in the 65-min group, 6 out of 9 had paraparesis/paraplegia; the remaining 3 reached normal function. The lone survivor after 90 min of LBCA was paraplegic. Nadir near-infrared spectroscopy of the collateral network values at Th8 and Th10 were 34 (±5) and 39 (±4), and they were reached within 35 min of SCP in both groups. Conclusions: An extended FET graft with LBCA and SCP durations >65 min at 28°C results in a poor outcome.

Objectives: The authors aimed to investigate the impact of severe bleeding and use of red blood cell (RBC) transfusion on the development of postoperative stroke after surgical (SAVR) and transcatheter aortic valve replacement (TAVR), taken from the FinnValve registry. Design: Nationwide, retrospective observational study. Setting: Five Finnish university hospitals participated in the registry. Participants: A total of 6,463 patients who underwent SAVR (n = 4,333) or TAVR (n = 2,130). Interventions: Patients who underwent TAVR or SAVR with a bioprosthesis with or without coronary revascularization. Measurements and Main Results: The incidence of postoperative stroke after SAVR was 3.8%. In multivariate analysis, the number of transfused RBC units (odds ratio [OR], 1.098; 95% confidence interval [CI], 1.064–1.133) was one of the independent predictors of postoperative stroke. The incidence of stroke increased, along with the severity of perioperative bleeding, according to the European Coronary Artery Bypass Grafting (E-CABG) bleeding grades were as follows: grade 0, 2.2% (reference group); grade 1, 3.4% (adjusted OR, 1.841; 95% CI, 1.105–3.066); grade 2, 5.5% (adjusted OR, 3.282; 95% CI, 1.948–5.529); and grade 3, 14.8% (adjusted OR, 7.103; 95% CI, 3.612–13.966). The incidence of postoperative stroke after TAVR was 2.5%. The number of transfused RBC units was an independent predictor of stroke after TAVR (adjusted OR, 1.155; 95% CI, 1.058–1.261). The incidence of postoperative stroke increased, along with the severity of perioperative bleeding, as stratified by the E-CABG bleeding grades: E-CABG grade 0, 1.7%; grade 1, 5.3% (adjusted OR, 1.270; 95% CI, 0.532–3.035); grade 2, 10.0% (adjusted OR, 2.898; 95% CI, 1.101–7.627); and grade 3, 30.0% (adjusted OR, 10.706; 95% CI, 2.389–47.987). Conclusions: Perioperative bleeding requiring RBC transfusion and/or reoperation for intrathoracic bleeding is associated with an increased risk of postoperative stroke after

Background: Acute type B aortic dissection (TBAD) is catastrophic event associated with significant mortality and lifelong morbidity. The optimal treatment strategy of TBAD is still controversial. Methods: This analysis includes patients treated for TBAD at the Helsinki University Hospital, Finland in 2007–2019. The endpoints were early and late mortality, and intervention of the aorta. Results: There were 205 consecutive TBAD patients, 59 complicated and 146 uncomplicated patients (mean age of 66 ± 14, females 27.8%). In-hospital and 30-day mortality rates were higher in complicated patients compared with uncomplicated patients with a statistically significant difference (p = 0.035 and p = 0.015, respectively). After a mean follow-up of 4.9 ± 3.8 years, 36 (25.0%) and 22 (37.9%) TBAD -related adverse events occurred in the uncomplicated and complicated groups, respectively (p = 0.066). Freedom from composite outcome was 83 ± 3% and 69 ± 6% at 1 year, 75 ± 4% and 63 ± 7% at 5 years, 70 ± 5% and 59 ± 7% at 10 years in the uncomplicated group and in the complicated group, respectively (p = 0.052). There were 25 (39.1%) TBAD-related deaths in the overall series and prior aortic aneurysm was the only risk factor for adverse aortic-related events in multivariate analysis (HR 3.46, 95% CI 1.72–6.96, p < 0.001). Conclusion: TBAD is associated with a significant risk of early and late adverse events. Such a risk tends to be lower among patients with uncomplicated dissection, still one fourth of them experience TBAD-related event. Recognition of risk factors in the uncomplicated group who may benefit from early aortic repair would be beneficial.

We aimed to investigate a hypothesised association between daily mean temperature and the risk of surgery for acute type A aortic dissection (ATAAD). For the period of 1 January 2005 until 31 December 2019, we collected daily data on mean temperatures and date of 2995 operations for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Using a two-stage time-series approach, we investigated the association between hot and cold temperatures relative to the optimal temperature and the rate of ATAAD repair in the selected cities. The relative risks (RRs) of cold temperatures (≤−5°C) and hot temperatures (≥21°C) compared to optimal temperature were 1.47 (95% CI: 0.72–2.99) and 1.43 (95% CI: 0.67–3.08), respectively. In line with previous studies, we observed increased risk at cold and hot temperatures. However, the observed associations were not statistically significant, thus only providing weak evidence of an association.

Background: Patients with severe aortic stenosis and left ventricular systolic dysfunction have a poor prognosis, and this may result in inferior survival also after aortic valve replacement. The outcomes of transcatheter and surgical aortic valve replacement were investigated in this comparative analysis. Methods: The retrospective nationwide FinnValve registry included data on patients who underwent transcatheter or surgical aortic valve replacement with a bioprosthesis for severe aortic stenosis. Propensity score matching was performed to adjust the outcomes for baseline covariates of patients with reduced (≤ 50%) left ventricular ejection fraction. Results: Within the unselected, consecutive 6463 patients included in the registry, the prevalence of reduced ejection fraction was 20.8% (876 patients) in the surgical cohort and 27.7% (452 patients) in the transcatheter cohort. Reduced left ventricular ejection fraction was associated with decreased survival (adjusted hazards ratio 1.215, 95%CI 1.067–1.385) after a mean follow-up of 3.6 years. Among 255 propensity score matched pairs, 30-day mortality was 3.1% after transcatheter and 7.8% after surgical intervention (p = 0.038). One-year and 4-year survival were 87.5% and 65.9% after transcatheter intervention and 83.9% and 69.6% after surgical intervention (restricted mean survival time ratio, 1.002, 95%CI 0.929–1.080, p = 0.964), respectively. Conclusions: Reduced left ventricular ejection fraction was associated with increased morbidity and mortality after surgical and transcatheter aortic valve replacement. Thirty-day mortality was higher after surgery, but intermediate-term survival was comparable to transcatheter intervention. Trial registration: The FinnValve registry ClinicalTrials.gov Identifier: NCT03385915.

The pulmonary artery catheter (PAC) is considered the gold standard for cardiac index monitoring. Recently new and less invasive methods to assess cardiac performance have been developed. The aim of our study was to assess the reliability of a non-invasive monitor utilizing bioreactance (Starling SV) and a non-calibrated mini-invasive pulse contour device (FloTrac/EV1000, fourth-generation software) compared to bolus thermodilution technique with PAC (TDCO) during off-pump coronary artery bypass surgery (OPCAB). In this prospective study, 579 simultaneous intra- and postoperative cardiac index measurements obtained with Starling SV, FloTrac/EV1000 and TDCO were compared in 20 patients undergoing OPCAB. The agreement of data was investigated by Bland–Altman plots, while trending ability was assessed by four-quadrant plots with error grids. In comparison with TDCO, Starling SV was associated with a bias of 0.13 L min−1 m−2 (95% confidence interval, 95% CI, 0.07 to 0.18), wide limits of agreement (LOA, − 1.23 to 1.51 L min−1 m−2), a percentage error (PE) of 60.7%, and poor trending ability. In comparison with TDCO, FloTrac was associated with a bias of 0.01 L min−1 m−2 (95% CI − 0.05 to 0.06), wide LOA (− 1.27 to 1.29 L min−1 m−2), a PE of 56.8% and poor trending ability. Both Starling SV and fourth-generation FloTrac showed acceptable mean bias but imprecision due to wide LOA and high PE, and poor trending ability. These findings indicate limited reliability in monitoring cardiac index in patients undergoing OPCAB.

Paraplegia is one of the most devastating complication after surgery for thoracic or thoracoabdominal aortic aneurysm. Despite the modern protection strategies utilized prior to, during and after the surgery, the risk of permanent paraplegia remains. In the repair of acute type A aortic dissection, selective cerebral perfusion (SCP) and lower body circulatory arrest (LBCA) are widely used operative methods to protect the central nervous system. The temperature used during SCP and LBCA has gradually been rising, which has not necessarily been beneficial for the spinal cord. New methods to protect the spinal cord and eliminate the possibility of permanent paraplegia are needed. Ischaemic preconditioning was first introduced in the 1980s in myocardial protection, while remote ischaemic preconditioning (RIPC) was introduced in the 1990s. In experimental studies, RIPC has proven to be an effective method to protect the spinal cord from ischaemia. Nonetheless, to date, there is no evidence for its potential in aortic aneurysm surgery in a clinical setting. The complete mechanism by which RIPC exerts its protective action is also unknown. Ischaemic priming by occluding the segmental arteries in an elective setting before the surgical treatment of the aortic aneurysm is a promising new method in protection of the spinal cord from ischaemic insult. However, to our knowledge, ischaemic priming of the spinal cord has not yet been attempted in an acute setting. The studies presented in this thesis were carried out as a chronic porcine study. The main objective of the studies was spinal cord protection during ischaemic insult. Study I demonstrated the protective effect of RIPC against spinal cord ischaemia. Pigs treated with RIPC exhibited a faster neurological recovery and preferable near-infrared spectroscopy values four hours after the spinal cord ischaemia compared to control pigs. In study II, acute ischaemic priming led to improved neurological recovery, lower lac, Tiivistelmä Rinta- tai rinta-vatsa-aortan aneurysman korjausleikkauksen yksi pahimmista mahdollisista komplikaatioista on pysyvä alaraajahalvaus huolimatta tänä päivänä käytössä olevista selkäytimen suojausmenetelmistä. Akuutin tyypin A aortan dissekaation korjausleikkauksen aikana selektiivinen aivoperfuusio ja verenkierron hypoterminen pysäyttäminen ovat usein käytettyjä metodeja suojata aivoja ja muita iskemialle alttiita kudoksia. Avustetun aivoperfuusion ja kehon hypotermisen verenkierron pysäytyksen lämpötilaraja on kuitenkin viime vuosien aikana hiljalleen noussut korkeammaksi, eikä tämä välttämättä ole selkäytimen suojauksen kannalta paras mahdollinen tilanne. Uusia selkäytimen suojausmenetelmiä tarvitaan edelleen, jotta pysyvän alaraajahalvauksen riski olisi mahdollisimman pieni. Sydämen suojaamisessa käytettävä iskeeminen esialtistus esiteltiin kirjallisuudessa 1980-luvulla. Seuraavalla vuosikymmenellä kirjallisuudessa esiteltiin myös etäinen iskeeminen esialtistus. Sittemmin kokeellisissa tutkimuksissa on osoitettu, että etäinen iskeeminen esialtistus suojaa selkäydintä iskeemiseltä vauriolta. Iskeemisestä esialtistuksesta tai etäisestä iskeemisestä esialtistuksesta ei toistaiseksi ole aikasempaa näyttöä aneurysmakirurgian yhteydessä. Niin ikään iskeemisen esialtistuksen tai etäisen iskeemisen esialtistuksen vaikutusmekanismia ei tunneta vielä tarkasti. Elektiivisessä aortan aneurysmakirurgiassa selkäytimen ja sen kollateraaliverenkierron iskeeminen esikäsittely on uusi ja lupaava keino suojata selkäydintä tulevan kirurgisen korjaustoimenpiteen aikana. Selkäytimen iskeemisen esikäsittelyn vaikutusta ei ole aikaisemmin tutkittu akuutissa tilanteessa. Tässä väitöskirjatyöksi tarkoitetussa tutkimuksessa tutkittiin ja selvitettiin selkäytimen suojaamista iskeemiseltä vauriolta. Tutkimus toteutettiin käyttäen apuna kokeellista eläinmallia. Ensimmäisessä tutkimuksessa osoitettiin etäisen iskeemisen esialtistuksen johtavan nopeampaan neurologiseen toipumiseen ja

Objectives: Acute type A aortic dissection (ATAAD) is a rare but severe condition, routinely treated with emergent cardiac surgery. Many surgeons have the notion that patients with ATAAD tend to come in clusters, but no studies have examined these observations. This investigation was undertaken to study the potential association between the lunar cycle and the incidence of ATAAD. Methods: We collected information on 2995 patients who underwent ATAAD surgery at centres from the Nordic Consortium for Acute Type A Aortic Dissection collaboration. We cross-referenced the time of surgery with lunar phase using a case-crossover design with 2 different definitions of full moon (>99% illumination and the 7-day full moon period). Results: The period when the moon was illuminated the most (99% definition) did not show any significant increase in incidence for ATAAD surgery. However, when the full moon period was compared with all other moon phases, it yielded a relative risk of 1.08 [95% confidence interval (CI) 1.00–1.17, P = 0.057] and, compared to waxing moon, only the relative risk was 1.11 (95% CI 1.01–1.23, P = 0.027). The peak incidence came 4–6 days after the moon was fully illuminated. Conclusions: This study found an overrepresentation of surgery for ATAAD during the full moon phase. The explanation for this is not known, but we speculate that sleep deprivation during full moon leads to a temporary increase in blood pressure, which in turn could trigger rupture of the aortic wall. While this finding is interesting, it needs to be corroborated and the clinical implications are debateable.

Objectives: We investigated whether the selective use of supracoronary ascending aorta replacement achieves late outcomes comparable to those of aortic root replacement for acute Stanford type A aortic dissection (TAAD). Methods: Patients who underwent surgery for acute type A aortic dissection from 2005 to 2018 at the Helsinki University Hospital, Finland, were included in this analysis. Late mortality was evaluated with the Kaplan–Meier method and proximal aortic reoperation, i.e. operation on the aortic root or aortic valve, with the competing risk method. Results: Out of 309 patients, 216 underwent supracoronary ascending aortic replacement and 93 had aortic root replacement. At 10 years, mortality was 33.8% after aortic root replacement and 35.2% after ascending aortic replacement (P = 0.806, adjusted hazard ratio 1.25, 95% confidence interval, 0.77–2.02), and the cumulative incidence of proximal aortic reoperation was 6.0% in the aortic root replacement group and 6.2% in the ascending aortic replacement group (P = 0.65; adjusted subdistributional hazard ratio 0.53, 95% confidence interval 0.15–1.89). Among 71 propensity score matched pairs, 10-year survival was 34.4% after aortic root replacement and 36.2% after ascending aortic replacement surgery (P = 0.70). Cumulative incidence of proximal aortic reoperation was 7.0% after aortic root replacement and 13.0% after ascending aortic replacement surgery (P = 0.22). Among 102 patients with complete imaging data [mean follow-up, 4.7 (3.2) years], the estimated growth rate of the aortic root diameter was 0.22 mm/year, that of its area 7.19 mm2/year and that of its perimeter 0.43 mm/year. Conclusions: When stringent selection criteria were used to determine the extent of proximal aortic reconstruction, aortic root replacement and ascending aortic replacement for type A aortic dissection achieved comparable clinical outcomes.

Background: Acute Stanford type A aortic dissection (TAAD) is a life-threatening condition. Surgery is usually performed as a salvage procedure and is associated with significant postoperative early mortality and morbidity. Understanding the patient’s conditions and treatment strategies which are associated with these adverse events is essential for an appropriate management of acute TAAD. Methods: Nineteen centers of cardiac surgery from seven European countries have collaborated to create a multicentre observational registry (ERTAAD), which will enroll consecutive patients who underwent surgery for acute TAAD from January 2005 to March 2021. Analysis of the impact of patient’s comorbidities, conditions at referral, surgical strategies and perioperative treatment on the early and late adverse events will be performed. The investigators have developed a classification of the urgency of the procedure based on the severity of preoperative hemodynamic conditions and malperfusion secondary to acute TAAD. The primary clinical outcomes will be in-hospital mortality, late mortality and reoperations on the aorta. Secondary outcomes will be stroke, acute kidney injury, surgical site infection, reoperation for bleeding, blood transfusion and length of stay in the intensive care unit. Discussion: The analysis of this multicentre registry will allow conclusive results on the prognostic importance of critical preoperative conditions and the value of different treatment strategies to reduce the risk of early adverse events after surgery for acute TAAD. This registry is expected to provide insights into the long-term durability of different strategies of surgical repair for TAAD. Trial registration: ClinicalTrials.gov Identifier: NCT04831073.

Epitranscriptomic modifications in RNA can dramatically alter the way our genetic code is deciphered. Cells utilize these modifications not only to maintain physiological processes, but also to respond to extracellular cues and various stressors. Most often, adenosine residues in RNA are targeted, and result in modifications including methylation and deamination. Such modified residues as N-6-methyl-adenosine (m⁶A) and inosine, respectively, have been associated with cardiovascular diseases, and contribute to disease pathologies. The Ischemic Heart Disease Epitranscriptomics and Biomarkers (IHD-EPITRAN) study aims to provide a more comprehensive understanding to their nature and role in cardiovascular pathology. The study hypothesis is that pathological features of IHD are mirrored in the blood epitranscriptome. The IHD-EPITRAN study focuses on m⁶A and A-to-I modifications of RNA. Patients are recruited from four cohorts: (I) patients with IHD and myocardial infarction undergoing urgent revascularization; (II) patients with stable IHD undergoing coronary artery bypass grafting; (III) controls without coronary obstructions undergoing valve replacement due to aortic stenosis and (IV) controls with healthy coronaries verified by computed tomography. The abundance and distribution of m⁶A and A-to-I modifications in blood RNA are charted by quantitative and qualitative methods. Selected other modified nucleosides as well as IHD candidate protein and metabolic biomarkers are measured for reference. The results of the IHD-EPITRAN study can be expected to enable identification of epitranscriptomic IHD biomarker candidates and potential drug targets.

The superiority of transcatheter (TAVR) over surgical aortic valve replacement (SAVR) for severe aortic stenosis (AS) has not been fully demonstrated in a real-world setting. This prospective study included 5706 AS patients who underwent SAVR from 2010 to 2012 and 2989 AS patients who underwent TAVR from 2017 to 2018 from the prospective multicenter observational studies OBSERVANT I and II. Early adverse events as well as all-cause mortality, major adverse cardiac and cerebrovascular events (MACCEs), and hospital readmission due to heart failure at 1-year were investigated. Among 1008 propensity score matched pairs, TAVR was associated with significantly lower 30-day mortality (1.8 vs. 3.5%, p = 0.020), stroke (0.8 vs. 2.3%, p = 0.005), and acute kidney injury (0.6 vs. 8.2%, p < 0.001) compared to SAVR. Moderate-to-severe paravalvular regurgitation (5.9 vs. 2.0%, p < 0.001) and permanent pacemaker implantation (13.8 vs. 3.3%, p < 0.001) were more frequent after TAVR. At 1-year, TAVR was associated with lower risk of all-cause mortality (7.9 vs. 11.5%, p = 0.006), MACCE (12.0 vs. 15.8%, p = 0.011), readmission due to heart failure (10.8 vs. 15.9%, p < 0.001), and stroke (3.2 vs. 5.1%, p = 0.033) compared to SAVR. TAVR reduced 1-year mortality in the subgroups of patients aged 80 years or older (HR 0.49, 95% CI 0.33–0.71), in females (HR 0.57, 0.38–0.85), and among patients with EuroSCORE II ≥ 4.0% (HR 0.48, 95% CI 0.32–0.71). In a real-world setting, TAVR using new-generation devices was associated with lower rates of adverse events up to 1-year follow-up compared to SAVR.

Objectives: The authors evaluated the outcome of adult patients with coronavirus disease 2019 (COVID-19)–related acute respiratory distress syndrome (ARDS) requiring the use of extracorporeal membrane oxygenation (ECMO). Design: Multicenter retrospective, observational study. Setting: Ten tertiary referral university and community hospitals. Participants: Patients with confirmed severe COVID-19–related ARDS. Interventions: Venovenous or venoarterial ECMO. Measurements and Main Results: One hundred thirty-two patients (mean age 51.1 ± 9.7 years, female 17.4%) were treated with ECMO for confirmed severe COVID-19–related ARDS. Before ECMO, the mean Sequential Organ Failure Assessment score was 10.1 ± 4.4, mean pH was 7.23 ± 0.09, and mean PaO₂/fraction of inspired oxygen ratio was 77 ± 50 mmHg. Venovenous ECMO was adopted in 122 patients (92.4%) and venoarterial ECMO in ten patients (7.6%) (mean duration, 14.6 ± 11.0 days). Sixty-three (47.7%) patients died on ECMO and 70 (53.0%) during the index hospitalization. Six-month all-cause mortality was 53.0%. Advanced age (per year, hazard ratio [HR] 1.026, 95% CI 1.000–1–052) and low arterial pH (per unit, HR 0.006, 95% CI 0.000–0.083) before ECMO were the only baseline variables associated with increased risk of six-month mortality. Conclusions: The present findings suggested that about half of adult patients with severe COVID-19–related ARDS can be managed successfully with ECMO with sustained results at six months. Decreased arterial pH before ECMO was associated significantly with early mortality. Therefore, the authors hypothesized that initiation of ECMO therapy before severe metabolic derangements subset may improve survival rates significantly in these patients. These results should be viewed in the light of a strict patient selection policy and may not be replicated in patients with advanced age or multiple comorbidities. Clinical Trial Registration: identifier, NCT04383678.

Acute Stanford Type A Aortic Dissection (ATAAD) is one of the most life-threatening acute pathologies in the human body; without treatment mortality nears 100%. One third of ATAAD patients suffer from cerebral malperfusion, and permanent ischaemic brain injury occurs in approximately 10% of patients. ATAAD is treated with open aortic arch surgery that involves cardiopulmonary bypass (CPB) and deep or profound (18–24 °C) hypothermic circulatory arrest (HCA); they can provide sufficient cerebral protection for up to 20–30 minutes by lowering the glucose and oxygen consumption of the brain. However, additional strategies on cerebral protection are still needed. ATAAD patients often present with shock, cardiac tamponade, malperfusion, or they could be still resuscitated while they are brought to the operation room. The rapid institution of antegrade cerebral blood flow through the CPB circuit is particularly vital for these patients and a new aortic cannulation strategy of direct true lumen cannulation after venous exsanguination (DTLC) was developed accordingly. However, associated normothermic circulatory arrest carries an inherent risk for neurologic sequalae. Our research group has studied the field of cerebral protection in aortic arch surgery extensively for the last 20 years through the use of a porcine model that closely simulates the clinical situation. One of the most promising neuroprotective strategies that has emerged from this research has been remote ischaemic preconditioning (RIPC), which is based on the notion that applying short ischaemia-reperfusion periods to a skeletal muscle increases ischaemic tolerance in other organs including the brain. Therefore, the present thesis studied whether DTLC with a 5-minute normothermic circulatory arrest was safe in terms of cerebral ischaemia (I), if RIPC would prolong the permissible period of HCA (II), and if it would improve the neurologic outcome combined with moderate hypothermia (III). The first stu, Tiivistelmä Tyypin A akuutti aortan dissekoituma (ATAAD) on edelleen yksi ihmiskehon hengenvaarallisimmista akuuteista sairaustiloista. Kolmanneksella potilaista aivojen verenkierto häiriintyy ja noin 10 prosenttia potilaista saa pysyvän aivovaurion joko itse sairaustilasta tai operaatiosta johtuen. ATAAD hoidetaan sydän-keuhkokoneen avulla syvässä (18–24°C) hypotermiassa eli alilämpöisyydessä tapahtuvan verenkierron seisautuksen (HCA) aikana. HCA vähentää sekä aivojen sokeriaineenvaihduntaa että hapen käyttöä, jolloin saadaan aikaa 20–30 minuuttia kirurgiselle toimenpiteelle riippuen lämpötilasta. ATAAD-potilaat ovat usein kriittisessä tilassa saapuessaan leikkaussaliin. Heillä voi olla verenkiertoshokki, verenkierto pääte-elimiin voi olla estynyt, tai heitä voidaan elvyttää. Erityisesti näiden potilaiden kohdalla on tärkeää edetä nopeasti kehonulkoiseen verenkiertoon sydän-keuhkokoneen avulla. Tätä varten kehitettiin uusi nousevan aortan kanylaatiomenetelmä. Potilaan verenkierto pysäytetään valuttamalla veri sydän-keuhkokoneeseen, nouseva aortta avataan ja aorttakanyyli asetetaan aorttaan näkökontrollissa (DTLC). Normaalissa kehon lämpötilassa tapahtuva verenkierron seisautus kuitenkin altistaa nopeasti neurologisille vaurioille. Tutkimusryhmämme on tutkinut aivojen suojaamista aortan kaaren kirurgian aikana jo 20 vuoden ajan kliinisesti merkittävän kokeellisen porsasmallin avulla. Etäinen iskeeminen esialtistus (RIPC) on osoittautunut lupaavaksi aivojen suojausmenetelmäksi. Siinä raajan lihaskudokseen kohdistetaan lyhyitä verenkierron pysäytyksiä ja palautuksia tavallisella verenpainemansetilla, minkä on osoitettu lisäävän aivojen sietokykyä hapenpuutteelta. Tässä väitöskirjassa tutkittiin, onko DTLC-kanylointimenetelmä aivojen kannalta turvallista, jos oletetaan sen kestävän viisi minuuttia (I). Lisäksi tutkimme, pidentääkö RIPC turvallista HCA:n kestoa (II) ja parantaako RIPC maltilliseen (24 °C) hypotermiaan yhdistettynä neurologista toipumista (III). Ensimmäi

Objectives: To compare the outcomes after surgical (SAVR) and transcatheter aortic valve replacement (TAVR) for severe stenosis of bicuspid aortic valve (BAV). Methods: We evaluated the early and mid-term outcome of patients with stenotic BAV who underwent SAVR or TAVR for aortic stenosis from the nationwide FinnValve registry. Results: The FinnValve registry included 6463 AS patients and 1023 (15.8%) of them had BAV. SAVR was performed in 920 patients and TAVR in 103 patients with BAV. In the overall series, device success after TAVR was comparable to SAVR (94.2% vs. 97.1%, p = 0.115). TAVR was associated with increased rate of mild-to-severe paravalvular regurgitation (PVR) (19.4% vs. 7.9%, p < 0.0001) and of moderate-to-severe PVR (2.9% vs. 0.7%, p = 0.053). When newer-generation TAVR devices were evaluated, mild-to-severe PVR (11.9% vs. 7.9%, p = 0.223) and moderate-to-severe PVR (0% vs. 0.7%, p = 1.000) were comparable to SAVR. Type 1 N-L and type 2 L-R/R-N were the BAV morphologies with higher incidence of mild-to-severe PVR (37.5% and 100%, adjusted for new-generation prostheses p = 0.025) compared to other types of BAVs. Among 75 propensity score-matched cohorts, 30-day mortality was 1.3% after TAVR and 5.3% after SAVR (p = 0.375), and 2-year mortality was 9.7% after TAVR and 18.7% after SAVR (p = 0.268). Conclusions: In patients with stenotic BAV, TAVR seems to achieve early and mid-term results comparable to SAVR. Type 1 N-L and type 2 L-R/R-N BAV morphologies had higher incidence of PVR. Larger studies evaluating different phenotypes of BAV are needed to confirm these findings. Clinical trial registration: ClinicalTrials.gov Identifier: NCT03385915.

Purpose: While extreme physical exertion is known to induce changes in the status of inflammation comparisons of the responses for various mediators of inflammation after acute bouts of high-intensity exercise have been limited. Subjects and Methods: We examined the responses in serum levels of novel inflammatory proteins, calprotectin, suPAR, CD163, and pro- and anti-inflammatory cytokines in 12 physically active volunteers (10 men, 2 women, mean age 37± 14 years) before and after completing various types of extreme physical exertion (marathon run, half-marathon run or 24-h cross-country skiing). For comparisons, the levels of the biomarkers were also measured at rest in 30 healthy controls (25 men, 5 women, mean age 42 ± 12 years) with low or sedentary activity. Results: Extreme physical exertion induced significant increases in serum calprotectin (p < 0.0005), suPAR (p < 0.01), CD163 (p < 0.05), IL-6 (p < 0.0005), IL-8 (p < 0.01) and IL-10 (p < 0.0005) (pre- vs 3h-post-exercise). These responses were found to normalize within 48 hours. While the increases in blood leukocytes were of similar magnitude following the different types of exercise, markedly more pronounced responses occurred in serum TNF-α (p < 0.01), IL-8 (p < 0.01) and CD163 (p < 0.05) in those with more intense activity. In 3-h post-exercise samples significant correlations were observed between serum calprotectin and IL-6 (rs = 0.720, p < 0.01), IL-10 (rs = 0.615, p < 0.05), TNF-α (rs = 0.594, p < 0.05), suPAR (rs = 0.587, p < 0.05) and blood leukocytes (rs = 0.762, p < 0.01). Conclusion: The present results suggest distinct exercise-intensity dependent changes in mediators of inflammation (including calprotectin, suPAR and CD163) following extreme physical exertion. Our findings indicate that there is a major reversible impact of high-intensity physical exertion on the status of inflammation.

The aim of this study was to evaluate all-cause mortality and aortic reoperations after surgery for Stanford type A aortic dissection (TAAD). We evaluated the late outcome of patients who underwent surgery for acute TAAD from January 2005 to December 2017 at the Helsinki University Hospital, Finland. We studied 309 patients (DeBakey type I TAAD: 89.3%) who underwent repair of TAAD. Aortic root repair was performed in 94 patients (30.4%), hemiarch repair in 264 patients (85.4%) and partial/total aortic arch repair in 32 patients (10.4%). Hospital mortality was 13.6%. At 10 years, all-cause mortality was 34.9%, and the cumulative incidence of aortic reoperation or late aortic-related death was 15.6%, of any aortic reoperation 14.6%, reoperation on the aortic root 6.6%, on the aortic arch, descending thoracic and/or abdominal aorta 8.7%, on the descending thoracic and/or abdominal aorta 6.4%, and on the abdominal aorta 3.8%. At 10 years, cumulative incidence of reoperation on the distal aorta was higher in patients with a diameter of the descending thoracic aorta ≥35 mm at primary surgery (cumulative incidence in the overall series: 13.2% vs. 4.0%, SHR 3.993, 95%CI 1.316–12.120; DeBakey type I aortic dissection: 13.6% vs. 4.5%, SHR 3.610, 95%CI 1.193–10.913; patients with dissected descending thoracic aorta: 15.8% vs. 5.9%, SHR 3.211, 95%CI 1.067–9.664). In conclusion, surgical repair of TAAD limited to the aortic segments involved by the intimal tear was associated with favorable survival and a low rate of aortic reoperations. However, patients with enlarged descending thoracic aorta at primary surgery had higher risk of late reoperation. Half of the distal aortic reinterventions were performed on the abdominal aorta.

Increasing data support transcatheter aortic valve implantation (TAVI) as a valid option over surgical aortic valve replacement (SAVR) in the treatment for severe aortic stenosis (AS) also in patients with low operative risk. However, limited data exist on the outcome of TAVI and SAVR in low-risk patients without coronary artery disease (CAD). The FinnValve registry included data on 6463 patients who underwent TAVI or SAVR with bioprosthesis between 2008 and 2017. Herein, we evaluated the outcome of low operative risk as defined by STS-PROM score <3% and absence of CAD, previous stroke and other relevant co-morbidities. Only patients who underwent TAVI with third-generation prostheses and SAVR with Perimount Magna Ease or Trifecta prostheses were included in this analysis. The primary endpoints were 30-day and 3-year all-cause mortality. Overall, 1,006 patients (175 TAVI patients and 831 SAVR patients) met the inclusion criteria of this analysis. Propensity score matching resulted in 140 pairs with similar baseline characteristics. Among these matched pairs, 30-day mortality was 2.1% in both TAVI and SAVR cohorts (p = 1.00) and 3-year mortality was 17.0% after TAVI and 14.6% after SAVR (p = 0.805). Lower rates of bleeding and atrial fibrillation, and shorter hospital stay were observed after TAVI. The need of new permanent pacemaker implantation and the incidence of early stroke did not differ between groups. In conclusion, TAVI using third-generation prostheses achieved similar early and mid-term survival compared with SAVR in low-risk patients without CAD.

Whether the subtype of atrial fibrillation affects outcomes after transcatheter aortic valve replacement for aortic stenosis is unclear. The nationwide FinnValve registry included 2130 patients who underwent primary after transcatheter aortic valve replacement for aortic stenosis during 2008–2017. Altogether, 281 (13.2%) patients had pre-existing paroxysmal atrial fibrillation, 651 (30.6%) had pre-existing non-paroxysmal atrial fibrillation and 160 (7.5%) were diagnosed with new-onset atrial fibrillation during the index hospitalization. The median follow-up was 2.4 (interquartile range: 1.6–3.8) years. Paroxysmal atrial fibrillation did not affect 30-day or overall mortality (p-values >0.05). Non-paroxysmal atrial fibrillation demonstrated an increased risk of overall mortality (hazard ratio: 1.61, 95% confidence interval: 1.35–1.92; p<0.001), but not 30-day mortality (p = 0.084). New-onset atrial fibrillation demonstrated significantly increased 30-day mortality (hazard ratio: 2.76, 95% confidence interval: 1.25–6.09; p = 0.010) and overall mortality (hazard ratio: 1.68, 95% confidence interval: 1.29–2.19; p<0.001). The incidence of early or late stroke did not differ between atrial fibrillation subtypes (p-values >0.05). In conclusion, non-paroxysmal atrial fibrillation and new-onset atrial fibrillation are associated with increased mortality after transcatheter aortic valve replacement for aortic stenosis, whereas paroxysmal atrial fibrillation has no effect on mortality. These findings suggest that non-paroxysmal atrial fibrillation rather than paroxysmal atrial fibrillation may be associated with structural cardiac damage which is of prognostic significance in patients with aortic stenosis undergoing transcatheter aortic valve replacement.

Background: There is limited information on the longer-term outcome after transcatheter aortic valve replacement (TAVR) with new-generation prostheses compared to surgical aortic valve replacement (SAVR). The aim of this study was to compare the mid-term outcomes after TAVR with Sapien 3 and SAVR with Perimount Magna Ease bioprostheses for severe aortic stenosis. Methods: In a retrospective study, we included patients who underwent transfemoral TAVR with Sapien 3 or SAVR with Perimount Magna Ease bioprosthesis between January 2008 and October 2017 from the nationwide FinnValve registry. Propensity score matching was performed to adjust for differences in the baseline characteristics. The Kaplan-Meir method was used to estimate late mortality. Results: A total of 2000 patients were included (689 in the TAVR cohort and 1311 in the SAVR cohort). Propensity score matching resulted in 308 pairs (STS score, TAVR 3.5 ± 2.2% vs. SAVR 3.5 ± 2.8%, p = 0.918). In-hospital mortality was 3.6% after SAVR and 1.3% after TAVR (p = 0.092). Stroke, acute kidney injury, bleeding and atrial fibrillation were significantly more frequent after SAVR, but higher rate of vascular complications was observed after TAVR. The cumulative incidence of permanent pacemaker implantation at 4 years was 13.9% in the TAVR group and 6.9% in the SAVR group (p = 0.0004). At 4-years, all-cause mortality was 20.6% for SAVR and 25.9% for TAVR (p = 0.910). Four-year rates of coronary revascularization, prosthetic valve endocarditis and repeat aortic valve intervention were similar between matched cohorts. Conclusions: The Sapien 3 bioprosthesis achieves comparable midterm outcomes to a surgical bioprosthesis with proven durability such as the Perimount Magna Ease. However, the Sapien 3 bioprosthesis was associated with better early outcome.

Importance: Transcatheter aortic valve replacement (TAVR) has been shown to be a valid alternative to surgical aortic valve replacement (SAVR) in patients at high operative risk with severe aortic stenosis (AS). However, the evidence of the benefits and harms of TAVR in patients at low operative risk is still scarce. Objective: To compare the short-term and midterm outcomes after TAVR and SAVR in low-risk patients with AS. Design, Setting, and Participants: This retrospective comparative effectiveness cohort study used data from the Nationwide Finnish Registry of Transcatheter and Surgical Aortic Valve Replacement for Aortic Valve Stenosis of patients at low operative risk who underwent TAVR or SAVR with a bioprosthesis for severe AS from January 1, 2008, to November 30, 2017. Low operative risk was defined as a Society of Thoracic Surgeons Predicted Risk of Mortality score less than 3% without other comorbidities of clinical relevance. One-to-one propensity score matching was performed to adjust for baseline covariates between the TAVR and SAVR cohorts. Exposures: Primary TAVR or SAVR with a bioprosthesis for AS with or without associated coronary revascularization. Main Outcomes and Measures: The primary outcomes were 30-day and 3-year survival. Results: Overall, 2841 patients (mean [SD] age, 74.0 [6.2] years; 1560 [54.9%] men) fulfilled the inclusion criteria and were included in the analysis; TAVR was performed in 325 patients and SAVR in 2516 patients. Propensity score matching produced 304 pairs with similar baseline characteristics. Third-generation devices were used in 263 patients (86.5%) who underwent TAVR. Among these matched pairs, 30-day mortality was 1.3% after TAVR and 3.6% after SAVR (P = .12). Three-year survival was similar in the study cohorts (TAVR, 85.7%; SAVR, 87.7%; P = .45). Interaction tests found no differences in terms of 3-year survival between the study cohorts in patients younger than vs older than 80 years or in patients who r

Aim: We investigated the outcomes of transcatheter (TAVR) and surgical aortic valve replacement (SAVR) in Finland during the last decade. Methods: The nationwide FinnValve registry included data from 6463 patients who underwent TAVR or SAVR with a bioprosthesis for aortic stenosis from 2008 to 2017. Results: The annual number of treated patients increased three-fold during the study period. Thirty-day mortality declined from 4.8% to 1.2% for TAVR (p = 0.011) and from 4.1% to 1.8% for SAVR (p = 0.048). Two-year survival improved from 71.4% to 83.9% for TAVR (p < 0.001) and from 87.2% to 91.6% for SAVR (p = 0.006). During the study period, a significant reduction in moderate-to-severe paravalvular regurgitation was observed among TAVR patients and a reduction of the rate of acute kidney injury was observed among both SAVR and TAVR patients. Similarly, the rate of red blood cell transfusion and severe bleeding decreased significantly among SAVR and TAVR patients. Hospital stay declined from 10.4 ± 8.4 to 3.7 ± 3.4 days after TAVR (p < 0.001) and from 9.0 ± 5.9 to 7.8 ± 5.1 days after SAVR (p < 0.001). Conclusions: In Finland, the introduction of TAVR has led to an increase in the invasive treatment of severe aortic stenosis, which was accompanied by improved early outcomes after both SAVR and TAVR.

Background: The outcome after weaning from postcardiotomy venoarterial extracorporeal membrane oxygenation (VA-ECMO) is poor. In this study, we investigated the prognostic impact of arterial lactate levels at the time of weaning from postcardiotomy VA. Methods: This analysis included 338 patients from the multicenter PC-ECMO registry with available data on arterial lactate levels at weaning from VA-ECMO. Results: Arterial lactate levels at weaning from VA-ECMO (adjusted OR 1.426, 95%CI 1.157–1.758) was an independent predictor of hospital mortality, and its best cutoff values was 1.6 mmol/L (<1.6 mmol/L, 26.2% vs. ≥ 1.6 mmol/L, 45.0%; adjusted OR 2.489, 95%CI 1.374–4.505). When 261 patients with arterial lactate at VA-ECMO weaning ≤2.0 mmol/L were analyzed, a cutoff of arterial lactate of 1.4 mmol/L for prediction of hospital mortality was identified (<1.4 mmol/L, 24.2% vs. ≥1.4 mmol/L, 38.5%, p = 0.014). Among 87 propensity score-matched pairs, hospital mortality was significantly higher in patients with arterial lactate ≥1.4 mmol/L (39.1% vs. 23.0%, p = 0.029) compared to those with lower arterial lactate. Conclusions: Increased arterial lactate levels at the time of weaning from postcardiotomy VA-ECMO increases significantly the risk of hospital mortality. Arterial lactate may be useful in guiding optimal timing of VA-ECMO weaning.