Acute Coronary Syndrome Subphenotypes Based on Repeated Biomarker Measurements in Relation to Long-Term Mortality Risk.

BACKGROUND: We aimed to identify patients with subphenotypes of postacute coronary syndrome (ACS) using repeated measurements of high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 in the year after the index admission, and to investigate their association with long-term mortality risk. METHODS AND RESULTS: BIOMArCS (BIOMarker Study to Identify the Acute Risk of a Coronary Syndrome) was an observational study of patients with ACS, who underwent high-frequency blood sampling for 1 year. Biomarkers were measured in a median of 16 repeated samples per individual. Cluster analysis was performed to identify biomarker-based subphenotypes in 723 patients without a repeat ACS in the first year. Patients with a repeat ACS (N=36) were considered a separate cluster. Differences in all-cause death were evaluated using accelerated failure time models (median follow-up, 9.1 years; 141 deaths). Three biomarker-based clusters were identified: cluster 1 showed low and stable biomarker concentrations, cluster 2 had elevated concentrations that subsequently decreased, and cluster 3 showed persistently elevated concentrations. The temporal biomarker patterns of patients in cluster 3 were similar to those with a repeat ACS during the first year. Clusters 1 and 2 had a similar and favorable long-term mortality risk. Cluster 3 had the highest mortality risk. The adjusted survival time ratio was 0.64 (95% CI, 0.44-0.93; P=0.018) compared with cluster 1, and 0.71 (95% CI, 0.39-1.32; P=0.281) compared with patients with a repeat ACS. CONCLUSIONS: Patients with subphenotypes of post-ACS with different all-cause mortality risks during long-term follow-up can be identified on the basis of repeatedly measured cardiovascular biomarkers. Patients with persistently elevated biomarkers have the worst outcomes, regardless of whether they experienced a repeat ACS in the first year.

Cocreation to Facilitate Communication and Collaboration Between Multidisciplinary Stakeholders in eHealth Research and Development: Case Study of the CARRIER (Coronary Artery Disease: Risk Estimations and Interventions for Prevention and Early Detection) Consortium.

BACKGROUND: Collaboration with diverse stakeholders in eHealth research is fundamental yet complex. Stakeholders from various disciplines do not "speak the same language" and have different levels of power and interest, resulting in contrasting objectives, priorities, and expectations. An approach to constructive communication and collaboration is necessary to overcome this complex dynamic. Cocreation, known in the field of eHealth most often to involve end users, may also be suitable for facilitating stakeholder engagement and alignment. OBJECTIVE: This paper provides insights into the application of cocreation, specifically in the early phases of research that focus on involving and aligning relevant stakeholders from different academic and professional backgrounds. METHODS: The case for this study was a group discussion with members of a multidisciplinary consortium that works on developing a personalized eHealth intervention for atherosclerotic cardiovascular disease. Using stakeholder mapping, health and medicine experts, big data scientists, software developers, and an innovation manager (N=8) were invited to participate. The discussion was based on a user scenario and structured according to the Six Thinking Hats of de Bono, representing 6 different types of thinking. The discussion was recorded, transcribed verbatim, and analyzed thematically with the use of ATLAS.ti software. RESULTS: First, informative and intuitive thinking served the preparatory purpose of familiarization with the project details and other participants. Second, positive and critical thinking constituted the body of the discussion and resulted in an in-depth conversation. Third, creative and organizational thinking were action oriented and focused on solutions and planning to safeguard future progress. The participants repeatedly reflected on various intervention-related themes, ranging from intervention content to technical functionalities and from legal requirements to implementation in practice. Moreover, project-related matters were discussed, including stakeholder management and time and budget constraints. CONCLUSIONS: This paper demonstrates how cocreation can be of value for multidisciplinary stakeholder engagement and alignment. Based on stakeholder mapping (with whom to discuss), a dream user scenario (what to discuss), and the Six Thinking Hats of de Bono (how to discuss), the participants shared information, discussed differences, searched for solutions, and moved toward a collective approach regarding intervention development. The lessons learned may further improve the understanding of how cocreation can contribute to multidisciplinary collaboration.

Reasons and predictors of non-participation in a personalized digital prehabilitation care trial for patients undergoing elective cardiothoracic surgery.

OBJECTIVES: Prehabilitation through a digital platform could preoperatively improve the physical and mental fitness of patients undergoing cardiothoracic surgery, thereby improving treatment outcomes. This study aimed to describe the reasons and predictors of non-participation in a personalized digital prehabilitation care trial (Digital Cardiac Counseling randomized controlled trial) for patients undergoing elective cardiothoracic surgery. METHODS: Adult patients scheduled for elective cardiothoracic surgery at the Maastricht University Medical Center+ were approached to participate in a digital prehabilitation care trial, in which patients were informed about their care pathway, monitored for symptom progression and screened for preoperative modifiable risk factors. Baseline characteristics of all eligible patients and reasons of non-participation were registered prospectively. Predictors of non-participation were determined using logistic regression. RESULTS: Between May 2020 and August 2022, 815 patients were eligible for participation; 421 (52%) did not participate in the personalized digital prehabilitation care trial. Reasons for non-participation were 'lack of internet access or insufficient digital skills' (32%), 'wishing no participation' (39%) and 'other reasons' (30%; e.g. vision or hearing impairments, analphabetism, language barriers). Independent predictors of non-participation were age [odds ratio (OR) 1.024 (1.003-1.046), P = 0.024], socioeconomic status [OR 0.267 (0.133-0.536), P < 0.001], current smoker [OR 1.823 (1.124-2.954), P = 0.015] and EuroSCORE II [OR 1.160 (1.042-1.292), P = 0.007]. CONCLUSIONS: Half of the eligible patients did not participate in a personalized digital prehabilitation care trial. Non-participants were vulnerable patients, with a more unfavourable risk profile and more modifiable risk factors, who could potentially benefit the most from prehabilitation.

BMI is not independently associated with coronary artery calcification in a large single-center CT cohort.

Objective: Obesity is associated with cardiovascular disease (CVD) and CVD mortality. However, previous reports showed a paradoxical protective effect in patients with known CVD referred as "obesity paradox". Therefore, the aim of the present study was to investigate the association of body mass index (BMI) with coronary artery calcification (CAC) in a large outpatient cardiac CT cohort. Methods: 4.079 patients who underwent cardiac CT between December 2007-May 2014 were analyzed. BMI and clinical risk factors (current smoking, diabetes mellitus type 2, family history, systolic blood pressure, lipid spectrum) were assessed. Missing values were imputed using multiple imputation. CAC extent was categorized as absent (0), mild (>0-100), moderate (>100-400) and severe (>400). Results: Multivariable multinomial logistic regression analysis, including all risk factors as independent variables, showed no association between BMI and CAC. Using absence of calcification as reference category, the odds ratios per unit increase in BMI were 1.01 for mild; 1.02 for moderate; and 1.00 for severe CAC (p-values ≥0.103). Conclusions: No statistically significant association was observed between BMI and CAC after adjustment for other risk factors.

Serially measured high-sensitivity cardiac troponin T, N-terminal-pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 for risk assessment after acute coronary syndrome: the BIOMArCS cohort.

AIMS: Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients. METHODS AND RESULTS: BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02-2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28-2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract). CONCLUSION: Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS. CLINICAL TRIAL REGISTRATION: The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106.

Digital Health Solutions to Reduce the Burden of Atherosclerotic Cardiovascular Disease Proposed by the CARRIER Consortium.

Digital health is a promising tool to support people with an elevated risk for atherosclerotic cardiovascular disease (ASCVD) and patients with an established disease to improve cardiovascular outcomes. Many digital health initiatives have been developed and employed. However, barriers to their large-scale implementation have remained. This paper focuses on these barriers and presents solutions as proposed by the Dutch CARRIER (ie, Coronary ARtery disease: Risk estimations and Interventions for prevention and EaRly detection) consortium. We will focus in 4 sections on the following: (1) the development process of an eHealth solution that will include design thinking and cocreation with relevant stakeholders; (2) the modeling approach for two clinical prediction models (CPMs) to identify people at risk of developing ASCVD and to guide interventions; (3) description of a federated data infrastructure to train the CPMs and to provide the eHealth solution with relevant data; and (4) discussion of an ethical and legal framework for responsible data handling in health care. The Dutch CARRIER consortium consists of a collaboration between experts in the fields of eHealth development, ASCVD, public health, big data, as well as ethics and law. The consortium focuses on reducing the burden of ASCVD. We believe the future of health care is data driven and supported by digital health. Therefore, we hope that our research will not only facilitate CARRIER consortium but may also facilitate other future health care initiatives.

Prevalence of a History of Metabolic or Hypertensive Pregnancy Disorder in Patients With Myocardial Infarction and Non-obstructive Coronary Arteries: An Observational Cohort Study.

Introduction: Myocardial infarction with non-obstructive coronary arteries (MINOCA) predominantly affects younger females. Women with a history of gestational hypertension (GH), preeclampsia (PE), and gestational diabetes mellitus (GDM) are subjected to an elevated lifetime risk of cardiovascular disease. However, data on the potential association between these obstetric complications and MINOCA is lacking. Therefore, the current study aimed to provide insight in the prevalence of metabolic and hypertensive pregnancy disorders (MHPD) in MINOCA patients and their clinical characteristics. Methods: In this observational cohort study conducted at the Zuyderland Medical Center and Maastricht University Medical Center in the Netherlands, patients were enrolled if they were identified as having MINOCA. Data on individual patient characteristics, laboratory results, electrocardiography as well as (non-)invasive imaging procedures were derived from the electronic health record system. Patients were asked to complete a questionnaire about prior MHPD including GDM, GH, and PE. Patients were grouped into those with MHPD and those with prior uncomplicated normotensive pregnancy (or pregnancies; NP). Results: After excluding patients without 1-year follow-up (n = 53), 86 female MINOCA patients remained eligible for analysis. Of the total female population, 25 (29.1%) patients had MHPD, including GH (n = 19; 22.1%), PE (n = 4; 4.7%), and GDM (n = 7; 8.1%). The MHPD patients showed higher rates of chronic hypertension (84.0 vs. 55.7%; p = 0.013), hypercholesterolemia (64.0 vs. 34.4%; p = 0.012), a family history of CVD (84.0 vs. 45.9%; p = 0.001), gout or rheumatic arthritis (16.0 vs. 1.6%; p = 0.024), and were more often non-smokers (45.8 vs. 78.3%; p = 0.004), compared to the NP patients. Moreover, MHPD patients were more likely to use cardiovascular medications at baseline. A trend toward no specific cause found for the MINOCA event was observed in MHPD patients compared to the NP group (64.0 vs. 42.6%, p = 0.072). Conclusion: A history of metabolic and hypertensive pregnancy disorders occurred in one-third of female MINOCA patients. In these patients, conventional cardiovascular risk factors were more prevalent compared to NP patients. In most MHPD patients, the specific cause for MINOCA remained unclear.

Unilateral left-sided thoracoscopic ablation of atrial fibrillation concomitant to minimally invasive bypass grafting of the left anterior descending artery.

OBJECTIVES: Thoracoscopic ablation for atrial fibrillation (AF) and minimally invasive direct coronary artery bypass (MIDCAB) with robot-assisted left internal mammary artery (LIMA) harvesting may represent a safe and effective alternative to more invasive surgical approaches via sternotomy. The aim of our study was to describe the feasibility, safety and efficacy of a unilateral left-sided thoracoscopic AF ablation and concomitant MIDCAB surgery. METHODS: Retrospective analysis of a prospectively gathered cohort was performed of all consecutive patients with AF and at least a critical left anterior descending artery (LAD) stenosis that underwent unilateral left-sided thoracoscopic AF ablation and concomitant off-pump MIDCAB surgery in the Maastricht University Medical Centre between 2017 and 2021. RESULTS: Twenty-three patients were included [age 69 years (standard deviation = 8), paroxysmal AF 61%, left atrial volume index 42 ml/m2 (standard deviation = 11)]. Unilateral left-sided thoracoscopic isolation of the left (n = 23) and right (n = 22) pulmonary veins and box (n = 21) by radiofrequency ablation was succeeded by epicardial validation of exit- and entrance block (n = 22). All patients received robot-assisted LIMA harvesting and off-pump LIMA-LAD anastomosis through a left mini-thoracotomy. The perioperative complications consisted of one bleeding of the thoracotomy wound and one aborted myocardial infarction not requiring intervention. The mean duration of hospital stay was 6 days (standard deviation = 2). After discharge, cardiac hospital readmission occurred in 4 patients (AF n = 1; pleural- and pericardial effusion n = 2, myocardial infarction requiring the percutaneous intervention of the LIMA-LAD n = 1) within 1 year. After 12 months, 17/21 (81%) patients were in sinus rhythm when allowing anti-arrhythmic drugs. Finally, the left atrial ejection fraction improved postoperatively [26% (standard deviation = 11) to 38% (standard deviation = 7), P = 0.01]. CONCLUSIONS: In this initial feasibility and early safety study, unilateral left-sided thoracoscopic AF ablation and concomitant MIDCAB for LIMA-LAD grafting is a feasible, safe and efficacious for patients with AF and a critical LAD stenosis.

Coronary calcium scoring as first-line test to detect and exclude coronary artery disease in patients presenting to the general practitioner with stable chest pain: protocol of the cluster-randomised CONCRETE trial.

INTRODUCTION: Identifying and excluding coronary artery disease (CAD) in patients with atypical angina pectoris (AP) and non-specific thoracic complaints is a challenge for general practitioners (GPs). A diagnostic and prognostic tool could help GPs in determining the likelihood of CAD and guide patient management. Studies in outpatient settings have shown that the CT-based coronary calcium score (CCS) has high accuracy for diagnosis and exclusion of CAD. However, the CT CCS test has not been tested in a primary care setting. In the COroNary Calcium scoring as fiRst-linE Test to dEtect and exclude coronary artery disease in GPs patients with stable chest pain (CONCRETE) study, the impact of direct access of GPs to CT CCS will be investigated. We hypothesise that this will allow for early diagnosis of CAD and treatment, more efficient referral to the cardiologist and a reduction of healthcare-related costs. METHODS AND ANALYSIS: CONCRETE is a pragmatic multicentre trial with a cluster randomised design, in which direct GP access to the CT CCS test is compared with standard of care. In both arms, at least 40 GP offices, and circa 800 patients with atypical AP and non-specific thoracic complaints will be included. To determine the increase in detection and treatment rate of CAD in GP offices, the CVRM registration rate is derived from the GPs electronic registration system. Individual patients' data regarding cardiovascular risk factors, expressed chest pain complaints, quality of life, downstream testing and CAD diagnosis will be collected through questionnaires and the electronic GP dossier. ETHICS AND DISSEMINATION: CONCRETE has been approved by the Medical Ethical Committee of the University Medical Center of Groningen. TRIAL REGISTRATION NUMBER: NTR 7475; Pre-results.

Coronary Artery Calcifications Are Associated With More Severe Multiorgan Failure in Patients With Severe Coronavirus Disease 2019 Infection: Longitudinal Results of the Maastricht Intensive Care COVID Cohort.

PURPOSE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is regarded as a multisystemic disease. Patients with preexisting cardiovascular disease have an increased risk for a more severe disease course. This study aimed to investigate if a higher degree of coronary artery calcifications (CAC) on a standard chest computed tomography (CT) scan in mechanically ventilated patients was associated with a more severe multiorgan failure over time. MATERIALS AND METHODS: All mechanically ventilated intensive care unit patients with SARS-CoV-2 infection who underwent a chest CT were prospectively included. CT was used to establish the extent of CAC using a semiquantitative grading system. We categorized patients into 3 sex-specific tertiles of CAC: lowest, intermediate, and highest CAC score. Daily, the Sequential Organ Failure Assessment (SOFA) scores were collected to evaluate organ failure over time. Linear mixed-effects regression was used to investigate differences in SOFA scores between tertiles. The models were adjusted for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, cardiovascular risk factors, and chronic liver, lung, and renal disease. RESULTS: In all, 71 patients were included. Patients in the highest CAC tertile had, on average, over time, 1.8 (0.5-3.1) points higher SOFA score, compared with the lowest CAC tertile ( P =0.005). This association remained significant after adjustment for age, sex, and APACHE II score (1.4 [0.1-2.7], P =0.042) and clinically relevant after adjustment for cardiovascular risk factors (1.3 [0.0-2.7], P =0.06) and chronic diseases (1.3 [-0.2 to 2.7], P =0.085). CONCLUSION: A greater extent of CAC is associated with a more severe multiorgan failure in mechanically ventilated coronavirus disease 2019 patients.

Using clinical prediction models to personalise lifestyle interventions for cardiovascular disease prevention: A systematic literature review.

This study aimed to systematically review the use of clinical prediction models (CPMs) in personalised lifestyle interventions for the prevention of cardiovascular disease. We searched PubMed and PsycInfo for articles describing relevant studies published up to August 1, 2021. These were supplemented with items retrieved via screening references of citations and cited by references. In total, 32 studies were included. Nineteen different CPMs were used to guide the intervention. Most frequently, a version of the Framingham risk score was used. The CPM was used to inform the intensity of the intervention in five studies (16 %), and the intervention's type in 31 studies (97 %). The CPM was supplemented with relative risk estimates for additional risk factors in three studies (9 %), and relative risk estimates for intervention effects in four (13 %). In addition to the estimated risk, the personalisation was determined using criteria based on univariable risk factors in 18 studies (56 %), a lifestyle score in three (9 %), and a physical examination index in one (3 %). We noted insufficient detail in reporting regarding the CPM's use in 20 studies (63 %). In 15 studies (47 %), the primary outcome was a CPM estimate. A statistically significant effect favouring the intervention to the comparator arm was reported in four out of eight analyses (50 %), and a statistically significant improvement compared to baseline in five out of seven analyses (71 %). Due to the design of the included studies, the effect of the use of CPMs is still unclear. Therefore, we see a need for future research.

Relation of Iron Status to Prognosis After Acute Coronary Syndrome.

Iron deficiency has been extensively researched and is associated with adverse outcomes in heart failure. However, to our knowledge, the temporal evolution of iron status has not been previously investigated in patients with acute coronary syndrome (ACS). Therefore, we aimed to explore the temporal pattern of repeatedly measured iron, ferritin, transferrin, and transferrin saturation (TSAT) in relation to prognosis post-ACS. BIOMArCS (BIOMarker study to identify the Acute risk of a Coronary Syndrome) is a prospective, multicenter, observational cohort study conducted in The Netherlands between 2008 and 2015. A total of 844 patients with post-ACS were enrolled and underwent high-frequency (median 17) blood sampling during 1 year follow-up. Biomarkers of iron status were measured batchwise in a central laboratory. We analyzed 3 patient subsets, including the case-cohort (n = 187). The primary endpoint (PE) was a composite of cardiovascular mortality and repeat nonfatal ACS, including unstable angina pectoris requiring revascularization. The association between iron status and the PE was analyzed using multivariable joint models. Mean age was 63 years; 78% were men, and >50% had iron deficiency at first sample in the case-cohort. After adjustment for a broad range of clinical variables, 1 SD decrease in log-iron was associated with a 2.2-fold greater risk of the PE (hazard ratio 2.19, 95% confidence interval 1.34 to 3.54, p = 0.002). Similarly, 1 SD decrease in log-TSAT was associated with a 78% increased risk of the PE (hazard ratio 1.78, 95% confidence interval 1.17 to 2.65, p = 0.006). Ferritin and transferrin were not associated with the PE. Repeated measurements of iron and TSAT predict risk of adverse outcomes in patients with post-ACS during 1 year follow-up. Trial Registration: The Netherlands Trial Register. Unique identifiers: NTR1698 and NTR1106. Registered at https://www.trialregister.nl/trial/1614 and https://www.trialregister.nl/trial/1073.

The Diagnostic and Prognostic Value of Coronary Calcium Scoring in Stable Chest Pain Patients: A Narrative Review.

BACKGROUND: Non-contrast computed tomography (CT) scanning allows for reliable coronary calcium score (CCS) calculation at a low radiation dose and has been well established as marker to assess the future risk of coronary artery disease (CAD) events in asymptomatic individuals. However, the diagnostic and prognostic value in symptomatic patients remains a matter of debate. This narrative review focuses on the available evidence for CCS in patients with stable chest pain complaints. METHOD: PubMed, Embase, and Web of Science were searched for literature using search terms related to three overarching categories: CT, symptomatic chest pain patients, and coronary calcium. The search resulted in 42 articles fulfilling the inclusion and exclusion criteria: 27 articles (n = 38 137 patients) focused on diagnostic value and 23 articles (n = 44 683 patients) on prognostic value of CCS. Of these, 10 articles (n = 21 208 patients) focused on both the diagnostic and prognostic value of CCS. RESULTS: Between 22 and 10 037 patients were included in the studies on the diagnostic and prognostic value of CCS, including 43 % and 51 % patients with CCS 0. The most evidence is available for patients with a low and intermediate pre-test probability (PTP) of CAD. Overall, the prevalence of obstructive CAD (OCAD, defined as a luminal stenosis of ≥ 50 % in any of the coronary arteries) as determined with CT coronary angiography in CCS 0 patients, was 4.4 % (n = 703/16 074) with a range of 0-26 % in individual studies. The event rate for major adverse cardiac events (MACE) ranged from 0 % to 2.1 % during a follow-up of 1.6 to 6.8 years, resulting in a high negative predictive value for MACE between 98 % and 100 % in CCS 0 patients. At increasing CCS, the OCAD probability and MACE risk increased. OCAD was present in 58.3 % (n = 617/1058) of CCS > 400 patients with percentages ranging from 20 % to 94 % and MACE occurred in 16.7 % (n = 175/1048) of these patients with percentages ranging from 6.9 % to 50 %. CONCLUSION: Accumulating evidence shows that OCAD is unlikely and the MACE risk is very low in symptomatic patients with CCS 0, especially in those with low and intermediate PTPs. This suggests a role of CCS as a gatekeeper for additional diagnostic testing. Increasing CCS is related to an increasing probability of OCAD and risk of cardiac events. Additional research is needed to assess the value of CCS in women and patient management in a primary healthcare setting. KEY POINTS: · A CCS of zero makes OCAD in patients at low-intermediate PTP unlikely. · A CCS of zero is related to a very low risk of MACE. · Categories of increasing CCS are related to increasing rates of OCAD and MACE. · Future studies should focus on the diagnostic and prognostic value of CCS in symptomatic women and the role in primary care. CITATION FORMAT: · Koopman MY, Willemsen RT, van der Harst P et al. The Diagnostic and Prognostic Value of Coronary Calcium Scoring in Stable Chest Pain Patients: A Narrative Review. Fortschr Röntgenstr 2022; 194: 257 - 265.

Last-minute cancellation of adult patients scheduled for cardiothoracic surgery in a large Dutch tertiary care centre.

OBJECTIVES: Unanticipated cancellation of a surgical procedure is a common problem, causing distress to the patient and increases in healthcare costs. However, limited evidence exists on the effects of last-minute cancellations of cardiothoracic surgical procedures in particular. The goal of this study was to gain insight into the prevalence of and the reasons for last-minute cancellations and to examine whether cancellation is associated with adverse medical outcomes. METHODS: Patients who were scheduled for elective cardiothoracic surgical procedures between January 2017 and June 2019 were evaluated. The reasons for the cancellations were assigned to the categories medically related or process related. We examined the differences in patient characteristics between those designated as no cancellation, medically related cancellations and process-related cancellations. Lastly, we examined the outcomes of patients who experienced a last-minute cancellation of a scheduled operation. RESULTS: A total of 2111 patients were included; of these, 301 (14.3%) had last-minute cancellations. In 78 (26%) cases, the cancellations were attributable to medical reasons (e.g. infection, comorbidities); 215 (71%) of the cancellations were process related (e.g. another patient in more urgent need of surgery, lack of staff). Almost 99% of the operations with a process-related cancellation were rescheduled compared to only 71.8% of the medically related cancelled operations (P < 0.001). Patients with a medically related cancellation had significantly higher 1-year mortality than patients who had no cancellation (unadjusted hazard ratio 2.50; 95% confidence interval, 1.30-4.78; P = 0.006); after adjustment for the EuroSCORE II, this effect remained significant. CONCLUSIONS: Last-minute cancellations were commonly seen in our cohort, and the reasons for cancellation were significantly related to adverse medical outcomes.

Temporal Evolution of Serum Concentrations of High-Sensitivity Cardiac Troponin During 1 Year After Acute Coronary Syndrome Admission.

Background Detailed insights in temporal evolution of high-sensitivity cardiac troponin following acute coronary syndrome (ACS) are currently missing. We aimed to describe and compare the post-ACS kinetics of high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT), and to determine their intra- and interindividual variation in clinically stable patients. Methods and Results We determined hs-cTnI (Abbott) and hs-cTnT (Roche) in 1507 repeated blood samples, derived from 191 patients with ACS (median, 8/patient) who remained free from adverse cardiac events during 1-year follow-up. Post-ACS kinetics were studied by linear mixed-effect models. Using the samples collected in the 6- to 12-month post-ACS time frame, patients were then considered to have chronic coronary syndrome. We determined (differences between) the average hs-cTnI and average hs-cTnT concentration, and the intra- and interindividual variation for both biomarkers. Compared with hs-cTnT, hs-cTnI peaked higher (median 3506 ng/L versus 494 ng/L; P<0.001) and was quicker below the biomarker-specific upper reference limit (16 versus 19 days; P<0.001). In the post-6-month samples, hs-cTnI and hs-cTnT showed modest correlation (rspearman=0.60), whereas the average hs-cTnT concentration was 5 times more likely to be above the upper reference limit than hs-cTnI. The intraindividual variations of hs-cTnI and hs-cTnT were 14.0% and 18.1%, while the interindividual variations were 94.1% and 75.9%. Conclusions Hs-cTnI peaked higher after ACS and was quicker below the upper reference limit. In the post-6-month samples, hs-cTnI and hs-cTnT were clearly not interchangeable, and average hs-cTnT concentrations were much more often above the upper reference limit than hs-cTnI. For both markers, the within-patient variation fell largely below beween-patient variation. Registration URL: https://www.trialregister.nl; unique identifiers: NTR1698 and NTR1106.

Geometric characteristics of bicuspid aortic valves.

OBJECTIVE: We studied the coaptation angles α and ß in bicuspid aortic valve geometry from computed tomography scan images. METHODS: In 45 patients, we calculated the coaptation angle α (the angle between the nonfused commissures crossing the center of coaptation), angle ß (between the nonfused commissures crossing the center of the reference circle), angles γ1 and γ2 and ε1 and ε2 (angle between the nonfused commissures and the coaptation point at the raphe or the perfect midpoint, respectively), the length of the raphe, the absolute and relative sinuses' surfaces (relative to the perfect circle and the percentage exceeding the ideal circle). Spearman correlation was employed to investigate the associations among all parameters. RESULTS: The coaptation angles α and ß were significantly different (P < .001). We found a significant correlation of α with the length of the raphe (P = .008), whereas ß was dependent on the position of the commissures. Both γ1 and γ2 (P = .04), or ε1 and ε2 (P < .001) significantly differed from each other and ε2 was the most constant angle, although its size geometrically depends on ß. The noncoronary was the largest sinus, and ß was the primary determinant of its increased size in bicuspid aortic valves with righ/left fusion pattern. CONCLUSIONS: The coaptation angle α is influenced by the length of the raphe, whereas angle ß is dependent on the position of the commissures. The position of the raphe can vary and is not always situated in the middle of the free edge. The position of the right/non commissure is variable, whereas the right/left commissure is more fixed.

Pericardial fat and its influence on cardiac diastolic function.

BACKGROUND: Pericardial fat (PF) has been suggested to directly act on cardiomyocytes, leading to diastolic dysfunction. The aim of this study was to investigate whether a higher PF volume is associated with a lower diastolic function in healthy subjects. METHODS: 254 adults (40-70 years, BMI 18-35 kg/m2, normal left ventricular ejection fraction), with (a)typical chest pain (otherwise healthy) from the cardiology outpatient clinic were retrospectively included in this study. All patients underwent a coronary computed tomographic angiography for the measurement of pericardial fat volume, as well as a transthoracic echocardiography for the assessment of diastolic function parameters. To assess the independent association of PF and diastolic function parameters, multivariable linear regression analysis was performed. To maximize differences in PF volume, the group was divided in low (lowest quartile of both sexes) and high (highest quartile of both sexes) PF volume. Multivariable binary logistic analysis was used to study the associations within the groups between PF and diastolic function, adjusted for age, BMI, and sex. RESULTS: Significant associations for all four diastolic parameters with the PF volume were found after adjusting for BMI, age, and sex. In addition, subjects with high pericardial fat had a reduced left atrial volume index (p = 0.02), lower E/e (p < 0.01) and E/A (p = 0.01), reduced e' lateral (p < 0.01), reduced e' septal p = 0.03), compared to subjects with low pericardial fat. CONCLUSION: These findings confirm that pericardial fat volume, even in healthy subjects with normal cardiac function, is associated with diastolic function. Our results suggest that the mechanical effects of PF may limit the distensibility of the heart and thereby directly contribute to diastolic dysfunction. Trial registration NCT01671930.

Biomarkers Associated With Aortic Valve Calcification: Should We Focus on Sex Specific Processes?

OBJECTIVE: Circulating biomarkers are useful in detection and monitoring of cardiovascular diseases. However, their role in aortic valve disease is unclear. Mechanisms are rapidly elucidated and sex differences are suggested to be involved. Therefore, we sought to identify biomarkers involved in aortic valve calcification (AVC) stratified by sex. METHODS: Blood samples of 34 patients with AVC (without further overt cardiovascular disease, including absence of hemodynamic consequences of valvular calcification) were compared with 136 patients without AVC. AVC was determined using computed tomography calcium scoring. Circulating biomarkers were quantified using a novel antibody-based method (Olink Proseek Multiplex Cardiovascular Panel I) and 92 biomarkers were compared between patients with and without AVC. RESULTS: In the overall population, Interleukin-1 Receptor Antagonist and pappalysin-1 were associated with increased and decreased odds of having AVC. These differences were driven by the male population [IL1RA: OR 2.79 (1.16-6.70), p = 0.022; PAPPA: OR 0.30 (0.11-0.84), p = 0.021]. Furthermore, TNF-related activation-induced cytokine (TRANCE) and fibroblast growth factor-23 were associated decreased odds of having AVC, and monocyte chemotactic protein-1 was associated with increased odds of having AVC [TRANCE: OR 0.32 (0.12-0.80), p = 0.015; FGF23: OR 0.41 (0.170-0.991), p = 0.048; MCP1: OR 2.64 (1.02-6.81), p = 0.045]. In contrast, galanin peptides and ST2 were associated with increased odds of having AVC in females [GAL: OR 12.38 (1.31-116.7), p = 0.028; ST2: OR13.64 (1.21-153.33), p = 0.034]. CONCLUSION: In this exploratory study, we identified biomarkers involved in inflammation, fibrosis and calcification which may be associated with having AVC. Biomarkers involved in fibrosis may show higher expression in females, whilst biomarkers involved in inflammation and calcification could associate with AVC in males.