Performance of D-dimer, cardiac troponin T, C-reactive protein, and NT-proBNP in prediction of long-term mortality in patients with suspected pulmonary embolism.

Aims: Pulmonary embolism (PE) is a common and potentially life-threatening condition requiring emergent diagnostic work-up. Despite wide use of biomarkers, little is known how they predict long-term prognosis of patients evaluated for suspected PE. Methods and results: We sought to assess the predictive performance of N-terminal pro-brain natriuretic peptide (NT-proBNP), C-reactive protein, fibrin D-dimer (FIDD), and cardiac troponin T (cTnT) in patients who underwent computed tomography pulmonary angiography (CTPA) for clinical suspicion of PE. The analysis involved 1001 patients, with 222 (22.2%) receiving a PE diagnosis at index imaging. Mean ages of patients with and without PE were 65.0 ± 17.1 and 64.5 ± 17.7 years, respectively. Median follow-up time was 3.9 years (interquartile range 2.9-4.9). Mortality was relatively high among both patients with and without documented PE (24.8% vs. 31.7%, P = 0.047). In patients with PE, only elevated NT-proBNP > 1000 ng/L and C-reactive protein > 50 mg/L levels at hospital admission were associated with higher mortality in an adjusted Cox regression model, but receiver operating characteristic (ROC) analysis showed no improved prediction compared to clinical variables. Among patients without PE, elevated NT-proBNP > 1000 ng/L, C-reactive protein > 10 mg/L, cTnT > 50 ng/L, and FIDD > 1.0 mg/L all predicted mortality. In an ROC analysis among patients without PE, models including NT-proBNP, cTnT, or C-reactive protein provided improved predictive performance. Conclusion: Patients evaluated for clinical suspicion of PE have high long-term mortality. Commonly used biomarkers provide long-term prognostic value in patients without PE. Given the relatively young age, it is vital to identify these high-risk patients and perform differential diagnosis work-up for alternative life-threatening conditions, and manage them as appropriate.

Association between aortic calcification and cytokine levels in patients with peripheral artery disease.

Aortic calcification-a marker of advanced atherosclerosis in large arteries-associates with cardiovascular mortality and morbidity. Little is known about the soluble inflamJarmatory profiles involved in large artery atherosclerosis. We investigated the correlation between aortic calcification in the abdominal aorta and cytokine levels in a cohort of peripheral artery disease patients. Aortic calcification index was measured from computed tomography exams and circulating cytokine levels were analyzed from blood serum samples of 156 consecutive patients prior to invasive treatment of peripheral artery disease. The study included 156 patients (mean age 70.7 years, 64 (41.0%) women). The mean ankle-brachial index (ABI) was 0.64 and the mean aortic calcification index (ACI) was 52.3. ACI was associated with cytokines cutaneous T-cell-attracting chemokine CTACK (ß 23.08, SE 5.22, p < 0.001) and monokine induced by gamma-interferon MIG (ß 9.40, SE 2.82, p 0.001) in univariate linear regression. After adjustment with cardiovascular risk factors, CTACK and MIG were independently associated with ACI, ß 17.9 (SE 5.22, p < 0.001) for CTACK and ß 6.80 (SE 3.33, p 0.043) for MIG. CTACK was significantly higher in the patients representing the highest ACI tertile (highest vs. middle, 7.53 vs. 7.34 Tukeys HSD p-value 0.023 and highest vs. lowest tertile 7.53 vs. 7.29, Tukeys HSD p-value 0.002). MIG was significantly higher in the highest tertile versus lowest (7.65 vs. 7.30, Tukeys HSD p-value 0.027). Cytokines CTACK and MIG are associated with higher ACI, suggesting that CTACK and MIG reflect atherosclerotic disease burden of the aorta. This might further suggest the possible association with other cardiovascular morbidities.

Vascular disease and ischemic stroke in patients with atrial fibrillation: Temporal trends and age-related differences.

BACKGROUND AND AIMS: We examined temporal trends and age-related differences in the prevalence of vascular diseases and in their association with ischemic stroke (IS) risk in patients with atrial fibrillation (AF). METHODS: The registry-based FinACAF study covered all patients with AF in Finland during 2007-2018. Incidence rate ratios (IRRs) of IS were computed with Poisson regression, and the interaction of vascular diseases with age and calendar year period was assessed. RESULTS: We identified 229,565 patients (50.0 % female; mean age 72.7 years) with incident AF. The overall prevalence of any vascular disease was 28.6 %, and the prevalence increased from 2007 to 2018, primarily among patients over 75 years. Overall, 5909 (2.6 %) patients experienced IS within the first year after AF diagnosis. Crude IS rate decreased continuously during the study period in both patients with and without vascular diseases, with the rates remaining consistently higher in patients with vascular diseases. Vascular diseases were independently associated with higher IS incidence among patients under 65 years (adjusted IRR with 95 % confidence interval 1.35 (1.10-1.66)), while among older patients, only peripheral artery disease was associated with IS, and other vascular conditions had no association with IS. No interactions between the calendar year period and vascular diseases with IS rate were observed. CONCLUSIONS: The association between vascular diseases and IS has remained stable over time and vascular diseases were independently associated with higher incidence of IS particularly in patients with AF under the age of 65.

Distinct circulating cytokine levels in patients with angiography-proven coronary artery disease compared to disease-free controls.

Background: Systemic inflammation has a critical role in the development of symptomatic coronary artery disease (CAD). Identification of inflammatory pathways may provide a platform for novel therapeutic approaches. We sought to determine whether there are differences in circulating cytokine profiles between patients with CAD and disease-free controls as well as according to the severity of the disease. Methods: Case-control study's population consisted of 452 patients who underwent diagnostic invasive coronary angiography due to clinical indications. We measured the serum concentrations of 48 circulating cytokines. Extent of CAD was assessed using the SYNTAX Score in 116 patients. Cytokine differences between groups were tested using Mann-Whitney U test and associations with CAD were explored using a logistic regression model. Results: Overall, 310 patients had angiographically verified CAD whereas 142 had no angiographically-detected coronary atherosclerosis. In multivariable logistic regression models adjusted for age, sex, hypertension, atrial fibrillation, history of smoking and treatment for diabetes and hyperlipidemia, increased levels of interleukin 9 (OR 1.359, 95%CI 1.046-1.766, p = 0.022), IL-17 (1.491, 95%CI 1.115-1.994, p = 0.007) and tumor necrosis factor alpha (TNF-α) (OR 1.440, 95%CI 1.089-1.904, p = 0.011) were independently associated with CAD. Patients with SYNTAX Score>22 had increased levels of stromal cell-derived factor 1 alfa (SDF-1α), beta-nerve growth factor (ß-NGF), IL-3 and decreased level of IL-17 compared to those with score ≤22 when adjusted for smoking and use of beta-blockers. Conclusions: Patients with CAD have distinct circulating cytokine profiles compared to disease-free controls. Distinct cytokines may have pivotal roles at different stages of coronary atherosclerosis. ClinicalTrials.gov Identifier: NCT03444259 (https://clinicaltrials.gov/study/NCT03444259).

Genetics, transcriptomics, metagenomics, and metabolomics in the pathogenesis and prediction of atrial fibrillation.

The primary cellular substrates of atrial fibrillation (AF) and the mechanisms underlying AF onset remain poorly characterized and therefore, its risk assessment lacks precision. While the use of omics may enable discovery of novel AF risk factors and narrow down the cellular pathways involved in AF pathogenesis, the work is far from complete. Large-scale genome-wide association studies and transcriptomic analyses that allow an unbiased, non-candidate-gene-based delineation of molecular changes associated with AF in humans have identified at least 150 genetic loci associated with AF. However, only few of these loci have been thoroughly mechanistically dissected, indicating that much remains to be discovered for targeted diagnostics and therapeutics. Metabolomics and metagenomics, on the other hand, add to the understanding of AF downstream of the primary substrate and integrate the signalling of environmental and host factors, respectively. These two rapidly developing fields have already provided several correlates of prevalent and incident AF that require additional validation in external cohorts and experimental studies. In this review, we take a look at the recent developments in genetics, transcriptomics, metagenomics, and metabolomics and how they may aid in improving the discovery of AF risk factors and shed light into the molecular mechanisms leading to AF onset.

Differential circulating cytokine profiles in acute coronary syndrome versus stable coronary artery disease.

Chronic inflammation plays a crucial role in coronary artery disease (CAD), but differences in specific cytokine profiles between acute coronary syndrome (ACS) and stable CAD remain unknown. We investigated cytokine differences between these two manifestations of CAD. The study included 308 patients with angiographically detected, hemodynamically significant CAD: 150 patients undergone angiography for ACS, 158 patients undergone angiography for stable CAD. To assess dynamic changes, 116 patients had index angiogram at least 3 months earlier. We measured the serum concentrations of 48 circulating cytokines. The ACS group had decreased interleukin (IL) 4 (p = 0.005), and increased IL-8 (p = 0.008), hepatocyte growth factor (HGF) (p < 0.001) and macrophage colony-stimulating factor (M-CSF) (p = 0.002) levels compared with the stable CAD group. Multivariable logistic regression revealed increased levels of HGF (OR 18.050 [95% CI 4.372-74.517], p < 0.001), M-CSF (OR 2.257 [1.375-3.705], p = 0.001) and IL-6 (OR 1.586 [1.131-2.224], p = 0.007), independently associated with ACS. In the post-angiography group, only diminished platelet-derived growth factor-BB levels in ACS-manifested patients were observed (OR 0.478, [0.279-0.818], p = 0.007). Cytokine profiles differ between ACS and stable CAD. Such differences seem to be mainly reversible within 3 months after ACS. Thus, targeting one or two cytokines only might not offer one-size fits all-therapeutic approach for CAD-associated inflammation.Trial registration: NCT03444259.

Transcriptomic and spatial dissection of human ex vivo right atrial tissue reveals proinflammatory microvascular changes in ischemic heart disease.

Cardiovascular disease plays a central role in the electrical and structural remodeling of the right atrium, predisposing to arrhythmias, heart failure, and sudden death. Here, we dissect with single-nuclei RNA sequencing (snRNA-seq) and spatial transcriptomics the gene expression changes in the human ex vivo right atrial tissue and pericardial fluid in ischemic heart disease, myocardial infarction, and ischemic and non-ischemic heart failure using asymptomatic patients with valvular disease who undergo preventive surgery as the control group. We reveal substantial differences in disease-associated gene expression in all cell types, collectively suggesting inflammatory microvascular dysfunction and changes in the right atrial tissue composition as the valvular and vascular diseases progress into heart failure. The data collectively suggest that investigation of human cardiovascular disease should expand to all functionally important parts of the heart, which may help us to identify mechanisms promoting more severe types of the disease.

Novel electrocardiographic classification for stroke prediction in atrial fibrillation patients undergoing cardioversion.

BACKGROUND: Abnormal conduction, structure, and function of the atrial myocardium predispose to atrial fibrillation (AF) and stroke. The usefulness of electrocardiographic indices in predicting stroke or systemic embolism (SSE) in patients undergoing cardioversion (CV) for AF remains unknown, especially in those at low estimated risk. OBJECTIVE: We systematically evaluated the performance of various P-wave abnormalities (PWAs) in predicting SSE 30 days after CV (derivation cohort) and in the long term (validation cohort). METHODS: Electrocardiograms (n = 1773) of AF patients undergoing an acute CV were manually reviewed. The 30-day post-CV data were used to derive a composite PWA variable. The electrocardiographic findings were validated by the long-term follow-up of patients with no anticoagulation. Electrocardiograms of 27 CAREBANK study patients with right atrial appendage biopsies were further analyzed for histopathologic validation. RESULTS: During data derivation, the best performance was found with a combination of prolonged P-wave (≥180 ms), deflected P-wave morphology in lead II, biphasic P-waves in inferior leads, or increased P-terminal force (≥80 mm·ms) as markers for extensive PWA. In the validation cohort, 219 of 874 (25.1%) had extensive PWA. During a median follow-up of 4.9 years, there were 51 patients (5.8%) with SSE in total. In a competing risk model, PWA predicted SSE (adjusted hazard ratio, 2.1 per category; 95% CI, 1.4-3.1; P < .001). Areas under the curve for SSE at 3 years were 0.77, 0.79, and 0.86 for PWA, CHA2DS2-VASc, score, and their combination, respectively. On histologic evaluation, extensive PWA was associated with interstitial fibrosis (P = .033). CONCLUSION: Novel electrocardiographic PWA classification provided additional prognostic insight in AF patients.

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

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

Positive Correlation Between Thoracic Aortic Diameter and Intracranial Aneurysm Size-An Observational Cohort Study.

OBJECTIVE: To investigate the association between intracranial aneurysms (IAs) and thoracic aortic diameter. METHODS: This observational cohort study examined thoracic aortic diameters in patients with IA. Patients were categorized by IA size (<7 mm and ≥7 mm) and IA status (ruptured/unruptured) based on radiologic findings. We investigated the association between thoracic aortic diameter and IA size and status using binary and linear regression as univariate and multivariable analyses. RESULTS: A total of 409 patients were included. Mean age was 60 (±11.7) years and 63% were women. Thoracic aortic diameters were greater among patients who had an IA ≥7 mm versus IA <7 mm (P < 0.05). In the univariate analysis, the diameter of the ascending aorta (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.02-1.129 per 1 mm; P = 0.002), aortic arch (OR, 1.10; 95% CI, 1.04-1.15 per 1 mm; P < 0.001), and descending aorta (OR, 1.10; 95% CI, 1.03-1.16 per 1 mm; P = 0.003) were associated with IAs ≥7 mm. In the multivariable regression model, larger ascending aorta (OR, 1.09; 95% CI, 1.01-1.17 per 1 mm; P = 0.018), aortic arch (OR, 1.12; 95% CI, 1.02-1.22 per 1 mm; P = 0.013), and descending aorta (OR, 1.20; 95% CI, 1.08-1.33 per 1 mm; P < 0.001) were associated with ruptured IA. CONCLUSIONS: Greater thoracic aortic diameters are associated with a higher risk of IA being larger than 7 mm and IA rupture. Exploring the concomitant growth tendency in IA and thoracic aorta provides a basis for future considerations regarding screening and risk management.

Fibrillatory wave amplitude and thromboembolic risk in non-anticoagulated patients with atrial fibrillation.

BACKGROUND: The benefit of oral anticoagulation in atrial fibrillation (AF) is well established for patients at elevated stroke risk, but less clear for those at intermediate risk. We investigated whether analysis of electrocardiogram (ECG) derived fibrillatory waves (F-waves) could help identify patients at risk for stroke and systemic embolism (SSE). METHODS: The Finnish Cardioversion (FinCV) study included patients not on permanent anticoagulation therapy who underwent cardioversion for an acute AF episode. We identified 739 individuals with a valid ECG and complete follow-up data. The maximum amplitudes of the F-waves in leads II and V1 were manually measured from the pre-procedure ECG. Patients were categorized into fine and coarse F-wave groups. The optimal lead and amplitude threshold for grouping were found in an events per person-years analysis. SSE were identified from the patient medical records until either anticoagulation was prescribed, AF was deemed chronic, the patient had deceased, or the end of follow-up. RESULTS: Overall 37 (5.0%) patients suffered SSE during the median follow-up time of 5.4 years (1.9-10.8). Measured from lead V1 the SSE rates per 100 person-years were 1.5 and 0.7 in fine and coarse F-wave groups, respectively. Fine F-waves were observed in 112 (15.2%). Baseline characteristics were similar between the groups. Fine F-wave predicted SSE in a competing risk analysis (SHR 2.34, 95%CI 1.12-4.87, p = .023). Analyses from lead II did not provide significant results. CONCLUSION: Electrocardiographic F-wave amplitude may provide additional information on stroke risk in patients with paroxysmal AF and borderline indications or contraindications for anticoagulation.

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.

Ischemic Stroke Temporally Associated With New-Onset Atrial Fibrillation: A Population-Based Registry-Linkage Study.

BACKGROUND: Limited data exist on the temporal relationship between new-onset atrial fibrillation (AF) and ischemic stroke and its impact on patients' clinical characteristics and mortality. METHODS: A population-based registry-linkage database includes all patients with new-onset AF in Finland from 2007 to 2018. Ischemic stroke temporally associated with AF (ISTAF) was defined as an ischemic stroke occurring within ±30 days from the first AF diagnosis. Clinical factors associated with ISTAF were studied with logistic regression and 90-day survival with Cox proportional hazards analysis. RESULTS: Among 229 565 patients with new-onset AF (mean age, 72.7 years; 50% female), 204 774 (89.2%) experienced no ischemic stroke, 12 209 (5.3%) had past ischemic stroke >30 days before AF, and 12 582 (5.8%) had ISTAF. The annual proportion of ISTAF among patients with AF decreased from 6.0% to 4.8% from 2007 to 2018. Factors associated positively with ISTAF were higher age, lower education level, and alcohol use disorder, whereas vascular disease, heart failure, chronic kidney disease cancer, and psychiatric disorders were less probable with ISTAF. Compared with patients without ischemic stroke and those with past ischemic stroke, ISTAF was associated with ≈3-fold and 1.5-fold risks of death (adjusted hazard ratios, 2.90 [95% CI, 2.76-3.04] and 1.47 [95% CI, 1.39-1.57], respectively). The 90-day survival probability of patients with ISTAF increased from 0.79 (95% CI, 0.76-0.81) in 2007 to 0.89 (95% CI, 0.87-0.91) in 2018. CONCLUSIONS: ISTAF depicts the prominent temporal clustering of ischemic strokes surrounding AF diagnosis. Despite having fewer comorbidities, patients with ISTAF had worse, albeit improving, survival than patients with a history of or no ischemic stroke. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04645537. URL: https://www.encepp.eu; Unique identifier: EUPAS29845.

The Role of MAPRE2 and Microtubules in Maintaining Normal Ventricular Conduction.

BACKGROUND: Brugada syndrome is associated with loss-of-function SCN5A variants, yet these account for only ≈20% of cases. A recent genome-wide association study identified a novel locus within MAPRE2, which encodes EB2 (microtubule end-binding protein 2), implicating microtubule involvement in Brugada syndrome. METHODS: A mapre2 knockout zebrafish model was generated using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated protein 9) and validated by Western blot. Larval hearts at 5 days post-fertilization were isolated for voltage mapping and immunocytochemistry. Adult fish hearts were used for ECG, patch clamping, and immunocytochemistry. Morpholinos were injected into embryos at 1-cell stage for knockdown experiments. A transgenic zebrafish line with cdh2 tandem fluorescent timer was used to study adherens junctions. Microtubule plus-end tracking and patch clamping were performed in human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) with MAPRE2 knockdown and knockout, respectively. RESULTS: Voltage mapping of mapre2 knockout hearts showed a decrease in ventricular maximum upstroke velocity of the action potential and conduction velocity, suggesting loss of cardiac voltage-gated sodium channel function. ECG showed QRS prolongation in adult knockout fish, and patch clamping showed decreased sodium current density in knockout ventricular myocytes and arrhythmias in knockout iPSC-CMs. Confocal imaging showed disorganized adherens junctions and mislocalization of mature Ncad (N-cadherin) with mapre2 loss of function, associated with a decrease of detyrosinated tubulin. MAPRE2 knockdown in iPSC-CMs led to an increase in microtubule growth velocity and distance, indicating changes in microtubule dynamics. Finally, knockdown of ttl encoding tubulin tyrosine ligase in mapre2 knockout larvae rescued tubulin detyrosination and ventricular maximum upstroke velocity of the action potential. CONCLUSIONS: Genetic ablation of mapre2 led to a decrease in voltage-gated sodium channel function, a hallmark of Brugada syndrome, associated with disruption of adherens junctions, decrease of detyrosinated tubulin as a marker of microtubule stability, and changes in microtubule dynamics. Restoration of the detyrosinated tubulin fraction with ttl knockdown led to rescue of voltage-gated sodium channel-related functional parameters in mapre2 knockout hearts. Taken together, our study implicates microtubule dynamics in the modulation of ventricular conduction.

Temporal Relation Between Myocardial Infarction and New-Onset Atrial Fibrillation: Results from a Nationwide Registry Study.

Myocardial infarction (MI) and atrial fibrillation (AF) are commonly seen in the same patient. In this study, we evaluated the temporal relations and prognosis of MI and AF. This is a substudy of the nationwide registry-based Finnish Anticoagulation in Atrial Fibrillation (FinACAF) study, comprising all Finnish patients with new-onset AF from 2010 to 2017. Patients with MI and AF were divided into groups depending on the temporal relation between the disease onsets: (1) MI before AF (MIAF), and (4) no MI. The 1-year mortality in the groups were studied with the Cox proportional hazards model. Of the 153,207 patients with new-onset AF (mean age 72.7 years, 50.0% women), 16,265 (10.6%) were diagnosed with MI. Altogether, 8,889 (54.7%) of the patients with MI were in the MIAF group. Of all MIs, 42.2% were diagnosed within 1 year from new-onset AF. The MI>AF group had the worst survival, with an adjusted hazard ratio for death of 3.08 (confidence interval [CI] 2.89 to 3.27) compared with patients without MI. For the MI

Antithrombotic Medication and Major Complications After Mechanical Aortic Valve Replacement.

Patients with mechanical aortic valve replacement (AVR) require lifelong vitamin K antagonist (VKA) therapy for stroke and systemic embolism prevention. However, VKA treatment predisposes patients to various types of bleeding. In the present study, we sought to assess the success of antithrombotic therapy and the occurrence and timing of strokes and bleeding events after mechanical AVR. A total of 308 patients who underwent isolated mechanical AVR were included in the study, and follow-up data were completed for 306 patients (99.4%). The median follow-up time was 7.3 (interquartile range 4.2 to 10.9) years. The risk for major bleeding was 5-fold compared with major stroke (6.2% vs 1.3% and 20.9% vs 4.0%, respectively; events rates 3.1 vs 0.5 per 100 patient-years, respectively) at 30-day and long-term follow-up, indicating good efficacy but inadequate safety of stroke prevention. At the time of the early postoperative major bleeding, the international normalized ratio was under the therapeutic range in 73.7% of the patients. However, most patients were on triple antithrombotic treatment consisting of subcutaneous enoxaparin, VKA, and a tail effect of discontinued aspirin. During the long-term follow-up, the most common site of bleeding was gastrointestinal (41.7%), followed by genitourinary bleeding (23.3%) and intracranial hemorrhage (18.3%). Furthermore, mortality was relatively high, with a 10-year survival estimate of 78.3%. In conclusion, although ischemic stroke is a well-identified adverse event after mechanical AVR, it seems that major bleeding is a frequent clinically relevant complication during perioperative and long-term follow-up. This finding underscores the recognition and management of modifiable bleeding risk factors.

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.