Indications and predictors for pacemaker implantation after isolated aortic valve replacement with bioprostheses : the CAREAVR study

OBJECTIVES: We sought to study the indications, long-term occurrence, and predictors of permanent pacemaker implantation (PPI) after isolated surgical aortic valve replacement with bioprostheses. METHODS: The CAREAVR study included 704 patients (385 females, 54.7%) without a preoperative PPI (mean +/- standard deviation age 75 +/- 7years) undergoing isolated surgical aortic valve replacement at 4 Finnish hospitals between 2002 and 2014. Data were extracted from electronic patient records. RESULTS: The follow-up was median 4.7years (range 1day to 12.3years). Altogether 56 patients received PPI postoperatively, with the median 507days from the operation (range 6days to 10.0years). The PPI indications were atrioventricular block (31 patients, 55%) and sick sinus syndrome (21 patients, 37.5%). For 4 patients, the PPI indication remained unknown. A competing risks regression analysis (Fine-Gray method), adjusted with age, sex, diabetes, coronary artery disease, preoperative atrial fibrillation (AF), left ventricular ejection fraction, New York Heart Association class, AF at discharge and urgency of operation, was used to assess risk factors for PPI. Only AF at discharge (subdistribution hazard ratio 4.34, 95% confidence interval 2.34-8.03) was a predictor for a PPI. CONCLUSIONS: Though atrioventricular block is the major indication for PPI after surgical aortic valve replacement, >30% of PPIs are implanted due to sick sinus syndrome during both short-term follow-up and long-term follow-up. Postoperative AF versus sinus rhythm conveys >4-fold risk of PPI.Peer reviewe

Preoperative paroxysmal atrial fibrillation predicts high cardiovascular mortality in patients undergoing surgical aortic valve replacement with a bioprosthesis: CAREAVR study

Background Preoperative permanent atrial fibrillation (AF) is associated with impaired outcome after surgical aortic valve replacement (SAVR). The impact of preoperative paroxysmal AF, however, has remained elusive. Purpose We assessed the impact of preoperative paroxysmal AF on outcome in patients undergoing SAVR with bioprosthesis. Methods A total of 666 patients undergoing isolated AVR with a bioprosthesis were included. Survival data was obtained from the national registry Statistics Finland. Patients were divided into three groups according to the preoperative rhythm: sinus rhythm (n = 502), paroxysmal AF (n = 90), and permanent AF (n = 74). Results Patients in the sinus rhythm and paroxysmal AF groups did not differ with respect to age (P = .484), gender (P = .402) or CHA(2)DS(2)-VASc score (P = .333). At 12-month follow-up, AF was present in 6.2% of sinus rhythm patients and in 42.4% of paroxysmal AF patients (P <.001). During follow-up, incidence of fatal strokes in the paroxysmal AF group was higher compared to sinus rhythm group (1.9 vs 0.4 per 100 patient-years, HR 4.4 95% Cl 1.8-11.0, P = .001). Cardiovascular mortality was higher in the paroxysmal AF group than in the sinus rhythm group (5.0 vs 3.0 per 100 patient-years, HR 1.70 95% CI 1.05-2.76, P = .03) and equal to patients in the permanent AF (5.0 per 100 patient-years). Conclusion Patients undergoing SAVR with bioprosthesis and history of paroxysmal AF had higher risk of developing permanent AF, cardiovascular mortality and incidence of fatal strokes compared to patients with preoperative sinus rhythm. Life-long anticoagulation should be considered in patients with a history of preoperative paroxysmal AF.Peer reviewe

Late incidence and recurrence of new-onset atrial fibrillation after isolated surgical aortic valve replacement

Publisher Copyright: © 2021 The AuthorsObjectives: Atrial fibrillation (AF) is a common complication after cardiac surgery. More knowledge is needed about long-term AF recurrence and adverse outcomes related to new-onset AF (NOAF) during the index hospitalization. Methods: A total of 1073 patients underwent isolated surgical aortic valve replacement at the 4 participating hospitals (2002-2014). After the exclusion of patients with a history of any preoperative AF, the final study population included 529 patients in the bioprosthetic and 253 patients in the mechanical valve prosthesis cohort. Median follow-up time was 5.4 (interquartile range, 3.4-8.2) years in the combined cohort. Results: Altogether 333 (42.6%) patients had in-hospital NOAF and 250 (32.0%) AF after hospital discharge. In the mechanical cohort, 64 (25.3%) experienced in-hospital NOAF and 74 (29.2%) AF after hospital discharge, whereas in the bioprosthetic cohort, 269 (50.9%) patients had in-hospital NOAF and 176 (33.3%) AF after hospital discharge. Patients with NOAF during the index hospital stay had a multifold risk of AF after hospital discharge in the combined cohort (hazard ratio [HR], 3.68; 95% confidence interval [CI], 2.82-4.81; P <.0001) as well as in both cohorts separately (bioprosthetic: HR, 4.35; 95% CI, 3.05-6.22; P <.001; mechanical: HR, 2.54; 95% CI, 1.59-4.03; P <.001). Patients with an in-hospital NOAF also had a significantly higher adjusted risk of death during the follow-up in the mechanical (HR, 2.05; 95% CI, 1.10-3.82; P =.025) and bioprosthetic (HR, 1.63; 95% CI, 1.17-2.28; P =.004) valve prosthesis cohorts. Conclusions: NOAF during the index hospitalization is associated with a 2- to 4-fold risk of later AF and 1.6- to 2.0-fold risk of all-cause mortality after mechanical and bioprosthetic surgical aortic valve replacement.Peer reviewe

Two novel direct SPIO labels and in vivo MRI detection of labeled cells after acute myocardial infarct

Background: Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. Cellular decay due hypoxia requires rapid and validated methods for possible therapeutic cell transplantation. Purpose: To develop direct and rapid superparamagnetic iron oxide (SPIO) cell label for a large-animal model and to assess in vivo cell targeting by magnetic resonance imaging (MRI) in an experimental AMI model. Material and Methods: Bone marrow mononuclear cells (BMMNCs) were labeled with SPIO particles using two novel direct labeling methods (rotating incubation method and electroporation). Labeling, iron incorporation in cells and label distribution, cellular viability, and proliferation were validated in vitro. An AMI porcine model was used to evaluate the direct labeling method (rotating incubation method) by examining targeting of labeled BMMNCs using MRI and histology. Results: Labeling (1 h) did not alter either cellular differentiation potential or viability of cells in vitro. Cellular relaxation values at 9.4 T correlated with label concentration and MRI at 1.5 T showing 894% signal reduction compared with non-labeled cells in vitro. In vivo, a high spatial correlation between MRI and histology was observed. The extent of macroscopic pathological myocardial changes (hemorrhage) correlated with altered function detected on MRI. Conclusion: We demonstrated two novel direct SPIO labeling methods and demonstrated the feasibility of clinical MRI for monitoring targeting of the labeled cells in animal models of AMI.Peer reviewe

Preoperative paroxysmal atrial fibrillation predicts high cardiovascular mortality in patients undergoing surgical aortic valve replacement with a bioprosthesis: CAREAVR study

Background Preoperative permanent atrial fibrillation (AF) is associated with impaired outcome after surgical aortic valve replacement (SAVR). The impact of preoperative paroxysmal AF, however, has remained elusive.Purpose We assessed the impact of preoperative paroxysmal AF on outcome in patients undergoing SAVR with bioprosthesis.Methods A total of 666 patients undergoing isolated AVR with a bioprosthesis were included. Survival data was obtained from the national registry Statistics Finland. Patients were divided into three groups according to the preoperative rhythm: sinus rhythm (n = 502), paroxysmal AF (n = 90), and permanent AF (n = 74).Results Patients in the sinus rhythm and paroxysmal AF groups did not differ with respect to age (P = .484), gender (P = .402) or CHA(2)DS(2)-VASc score (P = .333). At 12-month follow-up, AF was present in 6.2% of sinus rhythm patients and in 42.4% of paroxysmal AF patients (P Conclusion Patients undergoing SAVR with bioprosthesis and history of paroxysmal AF had higher risk of developing permanent AF, cardiovascular mortality and incidence of fatal strokes compared to patients with preoperative sinus rhythm. Life-long anticoagulation should be considered in patients with a history of preoperative paroxysmal AF.</p

Late incidence and recurrence of new-onset atrial fibrillation after isolated surgical aortic valve replacement

Atrial fibrillation (AF) is a common complication after cardiac surgery. More knowledge is needed about long-term AF recurrence and adverse outcomes related to new-onset AF (NOAF) during the index hospitalization.A total of 1073 patients underwent isolated surgical aortic valve replacement at the 4 participating hospitals (2002-2014). After the exclusion of patients with a history of any preoperative AF, the final study population included 529 patients in the bioprosthetic and 253 patients in the mechanical valve prosthesis cohort. Median follow-up time was 5.4 (interquartile range, 3.4-8.2) years in the combined cohort.Altogether 333 (42.6%) patients had in-hospital NOAF and 250 (32.0%) AF after hospital discharge. In the mechanical cohort, 64 (25.3%) experienced in-hospital NOAF and 74 (29.2%) AF after hospital discharge, whereas in the bioprosthetic cohort, 269 (50.9%) patients had in-hospital NOAF and 176 (33.3%) AF after hospital discharge. Patients with NOAF during the index hospital stay had a multifold risk of AF after hospital discharge in the combined cohort (hazard ratio [HR], 3.68; 95% confidence interval [CI], 2.82-4.81; P P P P = .025) and bioprosthetic (HR, 1.63; 95% CI, 1.17-2.28; P = .004) valve prosthesis cohorts.NOAF during the index hospitalization is associated with a 2- to 4-fold risk of later AF and 1.6- to 2.0-fold risk of all-cause mortality after mechanical and bioprosthetic surgical aortic valve replacement.</p

Occurrence and Classification of Cerebrovascular Events after Isolated Bioprosthetic Surgical Aortic Valve Replacement: A Competing Risk Analysis of the CAREAVR Study

Background: The long-term incidence of stroke and the proportion of cardioembolic events after bioprosthetic surgical aortic valve replacement (SAVR) remain largely unknown.Methods: The CAREAVR study sought to assess the rate of stroke and transient ischemic attack (TIA) in patients who underwent isolated surgical aortic valve replacement with a bioprosthesis at four Finnish university hospitals between 2002 and 2014. Data was collected retrospectively and included 721 patients. Median follow-up time was 4.8 [3.0–7.0] years.Results: At 5 years, freedom from stroke was 89.0%, from TIA 94.1%, and from stroke and TIA 83.7%. The median time between index procedure and stroke or TIA was 1.7 years [29 days–3.9 years]. Stroke was of cardioembolic origin in 44.4% of patients. In multivariable competing risk analysis, increased age (HR 1.03, 95%CI 1.00–1.06, p = 0.022), previous stroke or TIA (HR 1.75, 95%CI 1.14–2.70, p = 0.010), New York Heart Association (NYHA) class III or more (HR 1.51, 95%CI 1.01–2.24, p = 0.044) and insulin treatment at discharge (HR 1.20, 95%CI 1.09–3.64, p = 0.024) were independent predictors of stroke or TIA. Cerebrovascular events occurred in 47.2% of patients with ongoing anticoagulation therapy.Conclusion: In this study, the incidence of stroke in the early postoperative period after bioprosthetic SAVR was higher than previously documented. Almost half of strokes were of cardioembolic etiology. These findings highlight the need for the better prevention strategies for cardioembolic events after bioprosthetic SAVR.</p

CD3+ and CD8+ T-Cell-Based Immune Cell Score and PD-(L)1 Expression in Pulmonary Metastases of Microsatellite Stable Colorectal Cancer

The objective of this study was to evaluate the prognostic value of CD3+ and CD8+ based immune cell score (ICS), programmed death -1 (PD-1) and programmed death ligand -1 (PD-L1) in pulmonary metastases of proficient mismatch repair colorectal cancer (CRC) patients. A total of 101 pulmonary metastases and 62 primary CRC tumours were stained for CD3+, CD8+, PD-1 and PD-L1 expression. The prognostic value of ICS, PD-1/PD-L1 expression in 67 first pulmonary metastases and 61 primary CRC tumour was analysed. Comparative analysis was also performed between primary tumours and pulmonary metastases, as well as between T-cell densities and PD-1/PD-L1 expression. The 5-year overall survival rates of low, intermediate, and high ICS in pulmonary metastases were 10.0%, 25.5% and 47.0% (p = 0.046), respectively. Patients with high vs. low ICS in pulmonary metastases had a significantly better 5-year survival (adjusted HR 0.25, 95% CI 0.09-0.75, p = 0.013). High tumour cell PD-L1 expression in the pulmonary metastases was associated with improved survival (p = 0.024). Primary tumour CD8+ expression was significantly correlated with all T-cell densities in pulmonary metastases. Conclusion: The ICS evaluated from the resected pulmonary metastases of CRC showed significant prognostic value. High PD-L1 expression in pulmonary metastases is associated with favourable prognosis.publishedVersionPeer reviewe

Remote ischemic preconditioning as a means to protect the brain against hypothermic circulatory arrest:an experimental study on piglets

Abstract Open aortic arch surgery almost always requires a bloodless operating field which necessitates the use of hypothermic circulatory arrest. Hypothermic circulatory arrest is a technique where the core temperature of a patient is lowered so that the systemic blood circulation can be stopped momentarily. This can cause unwanted damage to the brain. The risk for neurological impairment is at its highest when corrective surgery has to be performed in emergency situations. This highlights the need for additional neuroprotective methods. Our research group has used a porcine model described in this thesis for about 12 years in various setups to study many neuroprotective hypotheses. We have tested and researched surgical and CPB strategies that could be useful in a HCA and aortic arch reconstruction setting. In this thesis we have combined both chronic surviving animal data with acute experiments and aim to shed light on the mechanisms and efficacy of RIPC as neuroprotective method. In our experimental model, RIPC provided a mitigation of inflammatory response and cerebral injury after prolonged HCA. In general, the collected data showed homogeneity as similar biochemical results were seen in study I and II. Also interestingly, study III and IV possibly shed some light as to the mechanisms of the neuroprotective effect seen in Study II. These results seem to corroborate each other in a logical way. In study I which was acute experiment we saw faster EEG recovery rates in the intervention group. Additionally we recorded beneficial biochemical changes from samples that were collected from the brain. In our chronic study, were the animals were followed for a 7 day period after hypothermic circulatory arrest, we saw a statistically significant neuroprotective effect of remote ischemic preconditioning. In studies III and IV we attempted to shed light on the mechanisms. Study III revealed that an altered oxygen usage profile during hypothermic circulatory arrest and recovery phase might have a role in the neuroprotection. In study IV we saw a reduced microcirculatory leukocyte accumulation in cerebrocortical vessels was noted using an intravital microscope. The intravital microscope also provided results that indicated a difference in the redox state of the mitochondria via NAD+/NADH autofluorescence measurements.Tiivistelmä Sydän- ja aorttakirurgiassa tarvitaan jossain tilanteissa täysin veretöntä leikkausaluetta. Verettömän leikkausalueen saavuttamiseksi joudutaan joskus turvautumaan potilaan elimistön jäähdytyksen jälkeiseen verenkierron pysäytykseen. Tämän menetelmän haittana on kuitenki aivokudokselle aiheutuva hapenpuute ja tästä mahdollisesti seuraava vaurioituminen. Vaurioitumisen riski on korkeimillaan erityisesti päivystyksellisissä tilanteissa. Tämän tutkimuksen tavoitteena on ollut selvittää, onko esialtistavalla raajaiskemialla kykyä suojata aivokudosta hapenpuutostilanteissa. Tutkimusryhmämme on viimeisen 12 vuoden aikana tutkinut sianporsailla eri keinoja, joilla voitaisiin parantaa aivojen suojausta sydän- ja aorttakirurgian aikana. Esialtistava raajaiskemia toteutetaan kiristämällä mansetti eläimen oikean takajalan ympärille. Tämän jälkeen mansetti täytetään viiden minuutin välein neljästi. Täyttökertojen välissä pidettään viiden minuutin tauko, jolloin mansetti on avatuna ja jalan verenkierto palautuu normaaliksi. Ensimmäisessä tutkimuksessamme totesimme, että esialtistava raajiskemia vaikuttaa aivojen sähkökäyrän toipumista nopeuttavasti. Toisessa tutkimuksessamme seurasimme koe-eläimiä seitsemän päivän ajan kokeen jälkeen. Tämän tutkimuksen yhteydessä toteutessa aivokudoksen mikroskooppiananalyysissä havaitsimme, että raajaiskemia vaikutti suojaavan aivokudosta hapenpuutteen aiheuttamilta aivovaurioilta. Kolmanessa tutkimuksessa selvitimme, että raajaiskemia vaikuttaa aivojen happipitoisuuteen sekä verenkierron pysäytyksen aikana että toipumisvaiheessa. Viimeisessä tutkimuksessa kuvasimme aivojen pintaverisuonia mikroskoopilla. Seurasimme kokeessa valkosolujen käyttäytymistä aivokudoksessa käyttäen fluoresoivia lääkeaineita. Havaitsimme, että raajaiskemiaryhmässä valkosoluja oli aivokudoksen pintaverisuonissa merkittävästi vähemmän. Lisäksi samalla menetelmällä tutkimme sitruunahappokiertoon osallistuvan NAD+/NADH parin suhteita autofluoresenssi ilmiöllä. Autofluorensenssi tutkimuksen tulokset viittaavat siihen, että mitokondrioiden hapetus/pelkistys kyky oli parempi raajaiskemia ryhmässä. Kokeissamme esialtistava raajaiskemia vähensi tulehdussolujen määrää aivokudoksessa sekä vähensi aivovauriota hapenpuutteen jälkeen