Prolonged Systemic Inflammatory Response Syndrome After Cardiac Surgery.

OBJECTIVES: Cardiac surgery induces systemic inflammatory response syndrome (SIRS), leading to higher morbidity and mortality. There are no individualized predictors for worse outcomes or biomarkers for the multifactorial, excessive inflammatory response. The interest of this study was to evaluate whether a systematic use of the SIRS criteria could be used to predict postoperative outcomes beyond infection and sepsis, and if the development of an exaggerated inflammation response could be observed preoperatively. DESIGN: The study was observational, with prospectively enrolled patients. SETTING: This was a single institution study in a hospital setting combined with laboratory findings. PARTICIPANTS: The study included a cohort of 261 volunteer patients. INTERVENTIONS: Patients underwent cardiac surgery with cardiopulmonary bypass, and were followed up to 90 days. Biomarker profiling was run preoperatively. MEASUREMENTS AND MAIN RESULTS: Altogether, 17 of 261 (6.4%) patients had prolonged SIRS, defined as fulfilling at least 2 criteria on 4 consecutive postoperative days. During hospitalization, postoperative atrial fibrillation (POAF) was found in 42.2% of patients, and stroke and transient ischemic attack in 3.8% of patients. Prolonged SIRS was a significant predictor of POAF (odds ratio [OR] 4.5, 95% CI 1.2-17.3), 90-day stroke (OR 4.5, 95% CI 1.1-18.0), and mortality (OR 10.7, 95% CI 1.7-68.8). Biomarker assays showed that preoperative nerve growth factor and interleukin 5 levels were associated with prolonged SIRS (OR 5.6, 95%, CI 1.4-23.2 and OR 0.7, 95%, CI 0.4-1.0, respectively). CONCLUSIONS: Nerve growth factor and interleukin 5 can be used to predict prolonged systemic inflammatory response, which is associated with POAF, stroke, and mortality.

Risk of fluid accumulation after cardiac surgery.

Objective: Patients undergoing heart surgery are at high risk of postoperative fluid accumulation due to long procedures and cardiopulmonary bypass. In the present study, we sought to investigate the prevalence of postoperative fluid accumulation and its relation to adverse events in patients undergoing cardiac surgery. Methods: CAREBANK is prospective, single-center cohort study focusing on the adverse events after cardiac surgery. The study population was divided into 2 groups based on 5% postoperative weight gain. All the in-hospital adverse events are registered on the database. The end points of the present study were length of hospital stay, length of intensive care unit stay, occurrence of new-onset atrial fibrillation after hospital major bleeding episodes major cardiac events, cerebrovascular events, and death. Three-month and 1-year follow-up data also include all major adverse events. Results: Altogether 1001 adult cardiac surgery patients were enrolled. The most frequent operations were coronary artery bypass grafting (56.3%). Five hundred fifty-four out of 939 (59.0%) patients had ≥5% weight gain during index hospitalization. Patients with a weight gain ≥5% were more likely to be women, have lower body mass index, had heart failure, and more often had preoperative atrial fibrillation. In-hospital period fluid accumulation was associated with reoperation due bleeding and longer total hospital stay. At 3 months' follow-up, weight gain 5% or more was associated with increased occurrence of new-onset atrial fibrillation, this was not reflected in the occurrence of strokes, transient ischemic attacks, or myocardial infarctions. Conclusions: Postoperative fluid excess is associated with adverse outcomes in cardiac surgery. Women, low-weight patients, and patients with cardiac failure or atrial fibrillation are prone to perioperative fluid accumulation.

Mechanocardiography-Based Measurement System Indicating Changes in Heart Failure Patients during Hospital Admission and Discharge.

Heart failure (HF) is a disease related to impaired performance of the heart and is a significant cause of mortality and treatment costs in the world. During its progression, HF causes worsening (decompensation) periods which generally require hospital care. In order to reduce the suffering of the patients and the treatment cost, avoiding unnecessary hospital visits is essential, as hospitalization can be prevented by medication. We have developed a data-collection device that includes a high-quality 3-axis accelerometer and 3-axis gyroscope and a single-lead ECG. This allows gathering ECG synchronized data utilizing seismo- and gyrocardiography (SCG, GCG, jointly mechanocardiography, MCG) and comparing the signals of HF patients in acute decompensation state (hospital admission) and compensated condition (hospital discharge). In the MECHANO-HF study, we gathered data from 20 patients, who each had admission and discharge measurements. In order to avoid overfitting, we used only features developed beforehand and selected features that were not outliers. As a result, we found three important signs indicating the worsening of the disease: an increase in signal RMS (root-mean-square) strength (across SCG and GCG), an increase in the strength of the third heart sound (S3), and a decrease in signal stability around the first heart sound (S1). The best individual feature (S3) alone was able to separate the recordings, giving 85.0% accuracy and 90.9% accuracy regarding all signals and signals with sinus rhythm only, respectively. These observations pave the way to implement solutions for patient self-screening of the HF using serial measurements.

Frequency of cardioversions as an additional risk factor for stroke in atrial fibrillation - the FinCV-4 study.

BACKGROUND: Patients with atrial fibrillation (AF) are selected for oral anticoagulation based on individual patient characteristics. There is little information on how clinical AF burden associates with the risk of ischaemic stroke or systemic embolism (SSE). The aim of this study was to explore the association of the frequency of cardioversions (CV) as a measure of clinical AF burden on the long-term SSE risk, with a focus on patients at intermediate stroke risk based on CHA2DS2-VASc score. For these patients, additional SSE risk stratification by assessing CV frequency may aid in the decision on whether to initiate oral anticoagulation. METHODS: This retrospective analysis of FinCV Study from years 2003-2010 included 2074 patients who were not using any oral anticoagulation (long term or temporary) after CVs and undergoing a total of 6534 CVs for AF from emergency departments of three hospitals. Two study groups were formed: high CV frequency (mean interval between CVs ≤12 months and low frequency (>12 months). RESULTS: A total of 107 SSEs occurred during a mean follow-up of 5.4 years. The event rates per 100 patient-years were 1.82 and 0.67 in high versus low CV frequency groups, respectively. After adjustment for CHA2DS2-VASc score, CV frequency independently predicted SSE (HR, 2.87 [95% CI, 1.47 to 5.64]; p = .002) at 3 years. Competing risk analysis also identified CV frequency (sHR, 2.70 [95% CI, 1.38-5.31]; p = .004) as an independent predictor for SSE. In patients with CHA2DS2-VASc score 1 and low CV frequency, the SSE risk was only 0.08 per 100 patient-years. CONCLUSIONS: Frequency of CVs for symptomatic AF episodes provides additional information on stroke risk in AF patients with CHA2DS2-VASc score 1.Key messagesThis retrospective study offers a unique opportunity to observe the natural course of AF patients with infrequent episodes of clinical arrhythmia when they were not using OAC (before introduction of CHA2DS2-VASc score).Stroke or systemic embolism rate was very low (0.08 per 100 patient-years) in patients with one CHA2DS2-VASc point who visited the emergency room for cardioversion less than once a year.Frequency of cardioversions can be used for additional risk stratification in patients at intermediate risk of stroke based on CHA2DS2-VASc score.

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

OBJECTIVES: 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.

Red blood cell transfusion induces abnormal HIF-1α response to cytokine storm after adult cardiac surgery.

Patients undergoing cardiac surgery develop a marked postoperative systemic inflammatory response. Blood transfusion may contribute to disruption of homeostasis in these patients. We sought to evaluate the impact of blood transfusion on serum interleukin-6 (IL-6), hypoxia induced factor-1 alpha (HIF-1α) levels as well as adverse outcomes in patients undergoing adult cardiac surgery. We prospectively enrolled 282 patients undergoing adult cardiac surgery. Serum IL-6 and HIF-1α levels were measured preoperatively and on the first postoperative day. Packed red blood cells were transfused in 26.3% of patients (mean 2.93 ± 3.05 units) by the time of postoperative sampling. Postoperative IL-6 levels increased over 30-fold and were similar in both groups (p = 0.115), whilst HIF-1α levels (0.377 pg/mL vs. 0.784 pg/mL, p = 0.002) decreased significantly in patients who received red blood cell transfusion. Moreover, greater decrease in HIF-1α levels predicted worse in-hospital and 3mo adverse outcome. Red blood cell transfusion was associated with higher risk of major adverse outcomes (stroke, pneumonia, all-cause mortality) during the index hospitalization. Red blood cell transfusion induces blunting of postoperative HIF-1 α response and is associated with higher risk of adverse thrombotic and pulmonary adverse events after cardiac surgery. Clinical Trial Registration ClinicalTrials.gov Identifier: NCT03444259.

Anticoagulation Therapy After Biologic Aortic Valve Replacement.

Objectives: Thromboembolism prophylaxis after biologic aortic valve replacement (BAVR) is recommended for 3 months postoperatively. We examined the continuation of oral anticoagulation (OAC) treatment and its effect on the long-term prognosis after BAVR. Methods: We used nation-wide register data from 4,079 individuals who underwent BAVR. We examined the association between warfarin and the non-vitamin K antagonist oral anticoagulant use with death, stroke and major bleeding in 2010 - 2016. Results: The risk of stroke was higher (HR 2.39, 95% CI 1.62 - 3.53, p < 0.001) and the risk of death was lower (HR 0.79, 95% CI 0.65 - 0.96, p = 0.016) in OAC-users compared to individuals without OAC. We observed no significant associations between OAC use and bleeding risk. Conclusion: OAC use after BAVR was associated with increased risk of stroke and decreased risk of death. These observational findings warrant validation in randomized controlled trials before any clinical conclusions can be drawn.

Minor troponin T elevation and mortality in patients with atrial fibrillation presenting to the emergency department.

BACKGROUND: There are limited data on the association of minor troponin elevation in unselected patients with atrial fibrillation (AF) presenting to the emergency department (ED) with adverse events. In this study, we sought to assess the early and mid-term mortality of these patients. METHODS: In this observational study, 2911 patients with AF were admitted to the ED. They were divided into 3 groups based on peak high-sensitivity troponin (TnT) levels: normal (<15 ng/L), 15-50 ng/L and 51-100 ng/L. The primary outcomes of this study were all-cause mortality at 30 days and 1 year. RESULTS: All-cause mortality was 6.7% (n = 196) at 30 days and 22.2% (n = 646) at 1 year. Mortality rate increased along with increasing levels of TnT irrespective of baseline covariates, primary discharge diagnosis and type of AF. A significant association between TnT levels and all-cause mortality was observed. The adjusted hazard ratio (HR) at 30 days was 6.02 (95% CI 2.62-13.83) for TnT 15-50 ng/L and 11.28 (95% CI 4.87-26.12) for TnT 51-100 ng/L (P<.001 for both) compared to TnT <15 ng/L. At 1 year, the adjusted HRs were 3.08 (95% CI 2.15-4.40) and 5.07 (95% CI 3.49-7.35), respectively (P < .001). When patients with TnT <15 ng/L were divided into two groups at the median value, TnT elevation of 10 to 14 ng/L was also associated with increased 1-year mortality (HR 2.51; 95% CI 1.09-5.74; P = .03). CONCLUSIONS: Among patients with AF admitted to the ED, increased TnT levels were associated with increased early and mid-term all-cause mortality irrespective of baseline covariates and type of AF.

Adverse events and survival with postpericardiotomy syndrome after surgical aortic valve replacement.

OBJECTIVES: Postpericardiotomy syndrome (PPS) is a relatively common complication after cardiac surgery. However, long-term follow-up data on the adverse events and mortality of PPS patients requiring invasive interventions are scarce. METHODS: We sought to assess the occurrence of mortality, new-onset atrial fibrillation (AF), cerebrovascular events, and major bleeds in PPS patients requiring medical attention in a combination database of 671 patients who underwent isolated surgical aortic valve replacement with a bioprosthesis (n = 361) or mechanical prosthesis (n = 310) between 2002 and 2014 (Cardiovascular Research Consortium-A Prospective Project to Identify Biomarkers of Morbidity and Mortality in Cardiovascular Interventional Patients [CAREBANK] 2016-2018). PPS was defined as moderate if it resulted in delayed hospital discharge, readmission, or medical therapy because of the symptoms; and severe if it required interventions for the evacuation of pleural or pericardial effusion. RESULTS: The overall incidence of PPS was 11.2%. Median time to diagnosis was 16 (interquartile range, 11-36) days. Severe PPS was diagnosed in 3.6% of patients. Severe PPS seemed to be associated with higher mortality (hazard ratio, 2.01; 95% confidence interval, 1.03-3.91; P = .040). Moderate or severe PPS increased the risk of new-onset AF during the early postoperative period (hazard ratio, 1.72; 95% confidence interval, 1.12-2.63; P = .012). No significant associations were found between PPS and cerebrovascular events or major bleeds during the follow-up. CONCLUSIONS: Patients with PPS requiring invasive interventions are at increased risk for mortality unlike those with mild to moderate forms of the disease. PPS requiring medical attention is associated with a higher AF rate during the early postoperative period but has no significant effect on the occurrence of major stroke, stroke or transient ischemic attack, or major bleeds during long-term follow-up.

Impact of functional studies on exome sequence variant interpretation in early-onset cardiac conduction system diseases.

AIMS: The genetic cause of cardiac conduction system disease (CCSD) has not been fully elucidated. Whole-exome sequencing (WES) can detect various genetic variants; however, the identification of pathogenic variants remains a challenge. We aimed to identify pathogenic or likely pathogenic variants in CCSD patients by using WES and 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines as well as evaluating the usefulness of functional studies for determining them. METHODS AND RESULTS: We performed WES of 23 probands diagnosed with early-onset (<65 years) CCSD and analysed 117 genes linked to arrhythmogenic diseases or cardiomyopathies. We focused on rare variants (minor allele frequency < 0.1%) that were absent from population databases. Five probands had protein truncating variants in EMD and LMNA which were classified as 'pathogenic' by 2015 ACMG standards and guidelines. To evaluate the functional changes brought about by these variants, we generated a knock-out zebrafish with CRISPR-mediated insertions or deletions of the EMD or LMNA homologs in zebrafish. The mean heart rate and conduction velocities in the CRISPR/Cas9-injected embryos and F2 generation embryos with homozygous deletions were significantly decreased. Twenty-one variants of uncertain significance were identified in 11 probands. Cellular electrophysiological study and in vivo zebrafish cardiac assay showed that two variants in KCNH2 and SCN5A, four variants in SCN10A, and one variant in MYH6 damaged each gene, which resulted in the change of the clinical significance of them from 'Uncertain significance' to 'Likely pathogenic' in six probands. CONCLUSION: Of 23 CCSD probands, we successfully identified pathogenic or likely pathogenic variants in 11 probands (48%). Functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants in patients with CCSD. SCN10A may be one of the major genes responsible for CCSD.

Population trends in aortic valve surgery in Finland between 2001 and 2016.

Objectives. To investigate nationwide changes in procedure rates, patient selection, and prognosis after all surgical aortic valve replacements. Design. Patients undergoing primary surgical aortic valve replacement between 2001 and 2016 were identified from three nationwide registers with compulsory reporting to examine trends in aortic valve surgery over four four-year time periods. Results. A total of 12,139 surgical aortic valve replacement procedures (mean age 61.9 ± 11.8 years, 39.1% women) were performed. The total number of biological valves increased from 1001 (42.9%) to 2526 (75.5%) from 2001-2004 to 2013-2016 (p < .001). During the first and last time periods the comorbidity burden increased; share of patients with hypertension increased from 37.5% to 46.9% (p < .001), diabetes from 14% to 16.5% (p = .01) and previous stroke from 5.2% to 7.2% (p = .01). The proportion of women undergoing surgery decreased from 40% to 36.1% from 2001-2004 to 2013-2016, respectively (p = .01). Overall 28-day mortality was 3.5%. In patients with biologic valve the multivariable-adjusted risk of short-term mortality decreased steadily in every four-year period from 2001-2004 to 2005-2008 (HR, 0.66; 95% CI 0.47-9.92), 2009-2012 (HR, 0.54; 95% CI, 0.39-0.75) and 2013-2016 (HR, 0.41; 95% CI, 0.29-0.58), whereas short-term mortality remained similar in patients with mechanical valve. The risk of four-year postoperative mortality after all surgical aortic valve replacements stayed constant. Conclusions. The use of biologic aortic valve prosthesis has increased from 2001 to 2016. The proportion of women has declined markedly. The short-term mortality has decreased and the long-term mortality has stayed constant despite increasing comorbidity burden.

Etiology of Minor Troponin Elevations in Patients with Atrial Fibrillation at Emergency Department-Tropo-AF Study.

Patients with atrial fibrillation (AF) presenting to the emergency department (ED) often have elevated cardiac troponin T (TnT) levels without evidence of type 1 myocardial infarction. We sought to explore the causes and significance of minor TnT elevations in patients with AF at the ED. All patients with AF admitted to the ED of Turku University Hospital between 1 March, 2013 and 11 April, 2016, and at least two TnT measurements, were screened. Overall, 2911 patients with a maximum TnT of 100 ng/L during hospitalization were analyzed. TnT was between 15 and 100 ng/L in 2116 patients. The most common primary discharge diagnoses in this group were AF (18.1%), infection (18.3%), ischemic stroke/transient ischemic attack (10.7%), and heart failure (5.0%). Acute coronary syndrome (ACS) was equally uncommon both in patients with normal TnT and elevated TnT (4.4% vs. 4.5%). Age ≥75 years, low estimated glomerular filtration rate (eGFR), high C-reactive protein (CRP), and hemoglobin <10.0 g/dL, were the most important predictors of elevated TnT. Importantly, TnT elevation was a very frequent (>93%) finding in elderly (≥75 years) AF patients with either low eGFR or high CRP. In conclusion, minor TnT elevations carry limited diagnostic value in elderly AF patients with comorbidities.

Distribution of ischemic strokes in patients with atrial fibrillation: The FibStroke Study.

BACKGROUND: We aimed to determine the relative frequency of affected cerebrovascular territories in patients with atrial fibrillation (AF) suffering an ischemic stroke. METHODS: Altogether, 1,976 patients who suffered their first-ever ischemic stroke during 2003-2012 and were diagnosed with AF either before or within 30 days after the event were included in this retrospective multicenter cohort study. Strokes were classified radiographically to be located either within the anterior or the posterior cerebrovascular territory, and the effect of the CHA2DS2-VASc score, oral anticoagulant (OAC) use, and timing of AF diagnosis on lesion localization was determined. RESULTS: The median age of the patients was 78.4 (interquartile range: 71.7-84.2) years, 1,137 (57.5%) of them were women, their mean CHA2DS2-VASc score was 3.5 (95% confidence interval: 3.4-3.5), 656 (33.2%) were receiving OAC drugs, and altogether, 1,450 (73%) had a previous AF diagnosis. The localization of ischemic lesions between the anterior and the posterior cerebrovascular territories was not affected by the timing of AF diagnosis (p = 0.46), use of OACs (p = 0.70), or the CHA2DS2-VASc score (p = 0.10). Within the anterior territory, altogether 774 strokes (53.2%) were located in the left hemisphere and 3 (0.2%) were bilateral. The timing of AF diagnosis (p = 0.84), use of OACs (p = 0.90), or the CHA2DS2-VASc score (p = 0.21) did not affect the location of the ischemic lesion between the hemispheres. CONCLUSIONS: The timing of AF diagnosis, use of OAC drugs, or the CHA2DS2-VASc score did not affect the distribution of ischemic strokes. Anterior territory strokes were slightly more often located within the left hemisphere.

Cardioversion for atrial fibrillation - how to prevent thromboembolic complications?

Cardioversion is an essential component of rhythm control strategy for atrial fibrillation. The thromboembolic risk of cardioversion is well established and the mechanisms behind the phenomenon have been comprehensively described. There are several clinical aspects that are important to take into consideration when assessing the safety of cardioversion. Before proceeding to cardioversion, the probability of early treatment failure and antiarrhythmic treatment options to prevent recurrences should be carefully evaluated to avoid the risks of repeated futile cardioversions. Effective periprocedural anticoagulation is the mainstay in thromboembolic complication prevention and the first week after rhythm conversion is the most vulnerable period in this respect. Early timing of cardioversion appears to be another important measure to decrease the risk of thromboembolic complications. Transoesophageal echocardiography is useful in clinical scenarios where early cardioversion is desirable due to debilitating clinical symptoms and a short duration of arrhythmia or the adequacy of preceding anticoagulation is uncertain. However, it does not lessen the need for effective anticoagulation after cardioversion. This review summarizes the recent scientific discoveries to improve the safety of cardioversion for atrial fibrillation. Key messages Cardioversion for atrial fibrillation entails a significant risk of thromboembolic complications, especially during the first week after the procedure. The intensity of periprocedural anticoagulation and the timing of cardioversion appear to be significant determinants of the risk of thromboembolism. Awareness of the clinical aspects influencing cardioversion safety should be raised.

Usefulness of the CHA2DS2-VASc and HAS-BLED Scores in Predicting the Risk of Stroke Versus Intracranial Bleeding in Patients With Atrial Fibrillation (from the FibStroke Study).

CHA2DS2-VASc and HAS-BLED scores stratify the risk of thromboembolic and bleeding events respectively in patients with atrial fibrillation. There is only little information on how they differentiate which of the 2 clinically most important complications (ischemic stroke [IS] or an intracranial bleeding [IB]) the patient is more prone to suffer. We evaluated both scores in patients with either of these major complications. The FibStroke Study collected data on all patients with atrial fibrillation with either an IS or an IB event between 2003 and 2012 in 4 Finnish hospital districts. Individual electronic patient records were manually reviewed to collect the study data. To assess the relative risk of IS and IB, an IS/IB-ratio was calculated by dividing the absolute number of ISs with the absolute number of IBs within each score category. A total of 3,816 (82.7%) ISs and 798 (17.3%) IBs were detected in 3,909 patients. In general, ISs occurred more often than IBs in patients on oral anticoagulation in each score category (ratio 1.6 to 5.1). The ratio decreased below 1, however, only with very high HAS-BLED scores (>4). Moreover, 221 ISs and 53 IBs occurred in patients with HAS-BLED > CHA2DS2-VASc, of whom only 19.7% were on anticoagulation. In conclusion, IS was the predominant intracranial event irrespective of CHA2DS2-VASc score, HAS-BLED score ≤4, or use of oral anticoagulation, also in patients with low estimated thromboembolic risk (CHA2DS2-VASc 0 to 1). Furthermore, the HAS-BLED score predicted the excess of IBs over ISs only at very high-risk levels.

Population trends in mitral valve surgery in Finland between 1997 and 2014: the finnish CVD register.

OBJECTIVES: Contemporary, nationwide data on trends in mitral valve surgery are scarce. Our aim was to investigate changes in procedure rates, patient selection, and post-procedural prognosis of open-heart mitral valve surgery in Finland. DESIGN: We combined data from three nationwide administrative registers with compulsory reporting. We identified patients who had undergone first-ever open-heart mitral valve surgery between 1997 and 2014 and followed them for adverse events. We examined trends in mitral valve surgery over three six-year time periods (1997-2002, 2003-2008, and 2009-2014). RESULTS: 3684 mitral valve procedures (mean age: 67.0 ± 10.9 years, 42.6% women) were performed in 1997-2014 in Finland. During this period, mitral valve repair operations became more common than replacements and we observed an increasing trend in the use of bioprosthetic valves. Between 1997-2002 and 2009-2014, the mean age of patients undergoing mitral valve surgery and the proportion of urgent surgeries increased (p < .001 for both). The proportion of women undergoing surgery decreased while the share of patients with hypertension (p = .023) or diabetes (p = .026) increased. The multivariable-adjusted risk of 28-day (hazard ratio, 0.55; 95% confidence interval, 0.37-0.83) and 6-year (hazard ratio, 0.80; 95% confidence interval, 0.67-0.97) post-operative mortality was lower in the last six-year period than in 1994-1998. CONCLUSIONS: Short- and long-term mortality of mitral valve surgery patients in Finland has decreased from 1997 to 2014 despite the patients being older and having more comorbidities. Understanding the changing characteristics and prognosis of these patients is important for the interpretation of previous and future cohort studies and trials.

Clinical manifestations and outcomes of severe warfarin overanticoagulation: from the EWA study.

INTRODUCTION: Severe warfarin overanticoagulation is a risk factor for bleeding, but there is little information on its manifestations, prognosis and factors affecting the outcome. We describe the manifestations and clinical outcomes of severe warfarin overanticoagulation in a large group of patients with atrial fibrillation (AF). MATERIAL AND METHODS: All international normalized ratio (INR) samples (n = 961,431) in the Turku University Hospital region between 2003 and 2015 were screened. A total of 412 AF patients with INR ≥9 were compared to 405 patients with stable warfarin anticoagulation for AF. Electronic patient records were manually reviewed to collect comprehensive data. RESULTS: Of the 412 patients with INR ≥9, bleeding was the primary manifestation in 105 (25.5%). Non-bleeding symptoms were recorded in 165 (40.0%) patients and 142 (34.5%) had no symptoms. A total of 17 (16.2%) patients with a bleed and 67 (21.8%) without bleeding died within 30 days after the event. Intracranial haemorrhage strongly predicted death within 30 days. Other significant predictors were non-bleeding symptoms, active malignancies, recent bleed, history of myocardial infarction, older age, renal dysfunction and a recent treatment episode. CONCLUSIONS: Bleeds are not the major determinant of the poor prognosis in severe overanticoagulation, as coincidental INR ≥9 findings also associate with high mortality. KEY MESSAGES Only a quarter of AF patients with INR ≥9 suffered a bleeding event and the clinical manifestation of INR ≥9 had a significant impact on patient outcome. The 30-day mortality rate in patients with INR ≥9 was high ranging from 9.2 to 32.7%. Several significant predictors of 30-day mortality after INR ≥9 were identified.