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Contains fulltext : 307416.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, BACKGROUND: Left ventricular ejection fraction (LVEF) demonstrates limited prognostic value for post-transcatheter aortic valve replacement (TAVR) outcomes. Evidence regarding the potential role of left ventricular global longitudinal strain (LV-GLS) in this setting is inconsistent. OBJECTIVES: The aim of this systematic review and meta-analysis of aggregated data was to evaluate the prognostic value of preprocedural LV-GLS for post-TAVR-related morbidity and mortality. METHODS: The authors searched PubMed, Embase, and Web of Science for studies investigating the association between preprocedural 2-dimensional speckle-tracking-derived LV-GLS and post-TAVR clinical outcomes. An inversely weighted random effects meta-analysis was adopted to investigate the association between LV-GLS vs primary (ie, all-cause mortality) and secondary (ie, major cardiovascular events [MACE]) post-TAVR outcomes. RESULTS: Of the 1,130 identified records, 12 were eligible, all of which had a low-to-moderate risk of bias (Newcastle-Ottawa scale). On average, 2,049 patients demonstrated preserved LVEF (52.6% ± 1.7%), but impaired LV-GLS (-13.6% ± 0.6%). Patients with a lower LV-GLS had a higher all-cause mortality (pooled HR: 2.01; 95% CI: 1.59-2.55) and MACE (pooled odds ratio [OR]: 1.26; 95% CI: 1.08-1.47) risk compared with patients with higher LV-GLS. In addition, each percentage point decrease of LV-GLS (ie, toward 0%) was associated with an increased mortality (HR: 1.06; 95% CI: 1.04-1.08) and MACE risk (OR: 1.08; 95% CI: 1.01-1.15). CONCLUSIONS: Preprocedural LV-GLS was significantly associated with post-TAVR morbidity and mortality. This suggests a potential clinically important role of pre-TAVR evaluation of LV-GLS for risk stratification of patients with severe aortic stenosis. (Prognostic value of left ventricular global longitudinal strain in patients with aortic stenosis undergoing Transcatheter Aortic Valve Implantation: a meta-analysis; CRD42021289626).

01 januari 2023, Item does not contain fulltext, OBJECTIVE: Midaortic syndrome (MAS) is narrowing of the distal thoracic and or abdominal aorta with congenital, inflammatory, or idiopathic aetiology. If left untreated, the prognosis is poor due to hypertensive complications. Follow up data after treatment are sparse, contrary to aortic coarctation. This study aimed to investigate hypertension during follow up after medical, endovascular, and surgical therapy in juveniles and adults. DATA SOURCES: A meta-analysis of case series and reports was performed, focusing on the incidence of hypertension during the follow up of juvenile (i.e., age 0-17 years) and adult MAS patients after medical, endovascular, or surgical therapy. REVIEW METHODS: Search queries were performed in PubMed, Embase, and Web of Science, and eligible articles underwent quality control. Descriptive statistics were reported based on available data, and individual patient data meta-analyses were performed using a one stage approach, accounting for clustering by case series or decades of reporting for case reports. For the meta-analysis, missing outcome and aetiology data were multiply imputed. RESULTS: The number of juveniles and adults who underwent endovascular therapy (33.7% vs. 27.3%; p = .42) and surgery (52.2% vs. 58.0%; p = .46) was similar. At baseline, 92.4% of juveniles and 87.5% of adults were hypertensive, decreasing to 23.2% and 24.1% during a follow up of 23 months (juveniles) and 18 months (adults), respectively. More hypertension was found compared with surgery in juveniles after endovascular therapy (38.1% vs. 10.8%; p = .020). Meta-analysis also demonstrated a trend for hypertension after endovascular therapy in juveniles, whereas hypertension was more prevalent following surgery in adults compared with endovascular therapy or medication. CONCLUSION: This review and meta-analysis investigated therapeutic options for MAS in juveniles and adults. It found that complications and hypertension during follow up were more common in juvenil

Item does not contain fulltext, BACKGROUND: Microvascular resistance reserve (MRR) is a new index to assess coronary microvascular (dys)function, which can be easily measured invasively using continuous thermodilution. In contrast to coronary flow reserve (CFR), MRR is independent of epicardial coronary disease and hemodynamic variations. Its measurement is accurate, reproducible, and operator independent. OBJECTIVES: The aim of this study was to establish the range of normal values for MRR and to determine an optimal cutoff point. METHODS: In this exploratory study in 214 patients with angina and no obstructive coronary artery disease, after excluding significant epicardial disease, all physiological parameters, such as fractional flow reserve, index of microvascular resistance, CFR, absolute blood flow, absolute microvascular resistance, and MRR, were measured. On the basis of concordant positive or concordant negative results of index of microvascular resistance and CFR, subgroups of patients were defined with high probability of either normal (n = 122) or abnormal (n = 24) microcirculatory function, and MRR was studied in these groups. RESULTS: Mean MRR in the "normal" group was 3.4 compared with a mean MRR of 1.9 in the "abnormal" group; these values were significantly different between the groups. MRR >2.7 ruled out coronary microvascular dysfunction (CMD) with a certainty of 96%, whereas MRR <2.1 indicated the presence of CMD with a similar high certainty of 96%. CONCLUSIONS: MRR is a suitable index to distinguish the presence or absence of CMD in patients with angina and no obstructive coronary artery disease. The present data indicate that an MRR of 2.7 virtually excludes the presence of CMD, while an MRR value <2.1 confirms its presence.

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01 juni 2023, Item does not contain fulltext, AIMS/HYPOTHESIS: It is generally recommended to reduce basal insulin doses after exercise to reduce the risk of post-exercise nocturnal hypoglycaemia. Based on its long t(½), it is unknown whether such adjustments are required or beneficial for insulin degludec. METHODS: The ADREM study (Adjustment of insulin Degludec to Reduce post-Exercise (nocturnal) hypoglycaeMia in people with diabetes) was a randomised controlled, crossover study in which we compared 40% dose reduction (D40), or postponement and 20% dose reduction (D20-P), with no dose adjustment (CON) in adults with type 1 diabetes at elevated risk of hypoglycaemia, who performed a 45 min aerobic exercise test in the afternoon. All participants wore blinded continuous glucose monitors for 6 days, measuring the incidence of (nocturnal) hypoglycaemia and subsequent glucose profiles. RESULTS: We recruited 18 participants (six women, age 38 ± 13 years, HbA(1c) 56 ± 8 mmol/mol [7.3 ± 0.8%], mean ± SD). Time below range (i.e. glucose <3.9 mmol/l) the night after the exercise test was generally low and occurrence did not differ between the treatment regimens. During the subsequent whole day, time below range was lower for D40 compared with CON (median [IQR], 0 [0-23] vs 18 [0-55] min, p=0.043), without differences in the number of hypoglycaemic events. Time above range (i.e. glucose >10 mmol/l) was greater for D20-P vs CON (mean ± SEM, 584 ± 81 vs 364 ± 66 min, p=0.001) and D40 (385 ± 72 min, p=0.003). CONCLUSIONS/INTERPRETATION: Post-exercise adjustment of degludec does not mitigate the risk of subsequent nocturnal hypoglycaemia in people with type 1 diabetes. Although reducing degludec reduced next-day time below range, this did not translate into fewer hypoglycaemic events, while postponing degludec should be avoided because of increased time above range. Altogether, these data do not support degludec dose adjustment after a single exercise bout. TRIAL REGISTRATION: EudraCT number 2019-004222-22 FUNDING: The stud

Contains fulltext : 293038.pdf (Publisher’s version ) (Open Access), AIMS: Patients with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS) are routinely transferred to the emergency department (ED). A clinical risk score with point-of-care (POC) troponin measurement might enable ambulance paramedics to identify low-risk patients in whom ED evaluation is unnecessary. The aim was to assess safety and healthcare costs of a pre-hospital rule-out strategy using a POC troponin measurement in low-risk suspected NSTE-ACS patients. METHODS AND RESULTS: This investigator-initiated, randomized clinical trial was conducted in five ambulance regions in the Netherlands. Suspected NSTE-ACS patients with HEAR (History, ECG, Age, Risk factors) score ≤3 were randomized to pre-hospital rule-out with POC troponin measurement or direct transfer to the ED. The sample size calculation was based on the primary outcome of 30-day healthcare costs. Secondary outcome was safety, defined as 30-day major adverse cardiac events (MACE), consisting of ACS, unplanned revascularization or all-cause death. : A total of 863 participants were randomized. Healthcare costs were significantly lower in the pre-hospital strategy (€1349 ± €2051 vs. €1960 ± €1808) with a mean difference of €611 [95% confidence interval (CI): 353-869; P < 0.001]. In the total population, MACE were comparable between groups [3.9% (17/434) in pre-hospital strategy vs. 3.7% (16/429) in ED strategy; P = 0.89]. In the ruled-out ACS population, MACE were very low [0.5% (2/419) vs. 1.0% (4/417)], with a risk difference of -0.5% (95% CI -1.6%-0.7%; P = 0.41) in favour of the pre-hospital strategy. CONCLUSION: Pre-hospital rule-out of ACS with a POC troponin measurement in low-risk patients significantly reduces healthcare costs while incidence of MACE was low in both strategies. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT05466591 and International Clinical Trials Registry Platform id NTR 7346.

Item does not contain fulltext, Prolonged exercise can induce cardiac troponin release. As single bouts of exercise may protect against cardiac injury, we explored the hypothesis that the magnitude of exercise-induced release of troponin attenuates upon successive days of exercise. We also examined whether effects of successive exercise bouts differ between healthy participants and individuals with cardiovascular risk factors (CVRFs) and established cardiovascular disease (CVD). We examined cardiac troponin I (cTnI) concentrations from whole venous blood samples collected from the antecubital vein (10 mL) in 383 participants (61 ± 14 yr) at rest and immediately following four consecutive days of long-distance walking (30-50 km/day). Participants were classified as either healthy (n = 222), CVRF (n = 75), or CVD (n = 86). Baseline cTnI concentrations were significantly higher in participants with CVD and CVRF compared with healthy (P < 0.001). Exercise-induced elevations in cTnI were observed in all groups following all days of walking compared with baseline (P < 0.001). Tobit regression analysis on absolute cTnI concentrations revealed a significant day × group interaction (P = 0.04). Following day 1 of walking, post hoc analysis showed that exercise-induced elevations in cTnI attenuated on subsequent days in healthy and CVRF, but not in CVD. Odds ratios for incident cTnI concentrations above the upper reference limit were significantly higher compared with baseline on day 1 for healthy participants (4.90 [95% CI, 1.58-15.2]) and participants with CVD (14.9 [1.86-125]) and remained significantly higher than baseline on all subsequent days in CVD. The magnitude of postexercise cTnI concentrations following prolonged walking exercise significantly declines upon repeated days of exercise in healthy individuals and those with CVRF, whereas this decline is not present in patients with CVD.NEW & NOTEWORTHY We show the magnitude of postexercise cardiac troponin concentrations following prolonged walking

Contains fulltext : 295984.pdf (Publisher’s version ) (Open Access), AIMS: Paravalvular regurgitation (PVR) is a common complication after transcatheter aortic valve replacement (TAVR) that poses an increased risk of rehospitalization for heart failure and mortality. The aim of this study was to assess the accuracy of haemodynamic indices to predict relevant PVR. METHODS AND RESULTS: In this prospective single-centre clinical trial, four haemodynamic indices of PVR measured during TAVR were assessed for their correlation with gold standard cardiac magnetic resonance (CMR)-derived regurgitant fraction (CMR-RF) at 1 month follow-up: diastolic delta (DD), heart rate-adjusted diastolic delta (HR-DD), aortic regurgitation index (ARI), and aortic regurgitation index ratio (ARI ratio). These haemodynamic indices were analysed for their ability to predict relevant PVR (defined as CMR-RF > 20%) using receiver operating characteristic (ROC) curves with corresponding area under the ROC curves (AUCs). A total of 77 patients were included and had CMR performed 41 ± 14 days after TAVR. Mean CMR-RF was 12.4 ± 9.3%. Fifteen (19.5%) patients had CMR-RF > 20%. DD had the best correlation with CMR-RF and the highest AUC to predict relevant PVR (0.82; 95% CI, 0.72-0.92), followed by HR-DD (AUC 0.78; 95% CI, 0.67-0.89), ARI (AUC 0.78; 95% CI, 0.66-0.89), and ARI ratio (AUC 0.65; 95% CI, 0.49-0.81). The optimal cut-off value for DD was 32 mmHg, with sensitivity of 69% and specificity of 77% in predicting relevant PVR. CONCLUSION: DD measured during TAVR best predicts relevant PVR. Correction for heart rate (HR-DD) or systolic blood pressure (ARI, ARI ratio) did not improve this predictive value.

Contains fulltext : 296185.pdf (Publisher’s version ) (Open Access), AIMS: Heyde syndrome is the co-occurrence of aortic stenosis, acquired von Willebrand syndrome, and gastrointestinal bleeding. Aortic valve replacement has been demonstrated to resolve all three associated disorders. A systematic review and meta-analysis were performed to obtain best estimates of the effect of aortic valve replacement on acquired von Willebrand syndrome and gastrointestinal bleeding. METHODS AND RESULTS: A literature search was performed to identify articles on Heyde syndrome and aortic valve replacement up to 25 October 2022. Primary outcomes were the proportion of patients with recovery of acquired von Willebrand syndrome within 24 h (T1), 24-72 h (T2), 3-21 days (T3), and 4 weeks to 2 years (T4) after aortic valve replacement and the proportion of patients with cessation of gastrointestinal bleeding. Pooled proportions and risk ratios were calculated using random-effects models. Thirty-three studies (32 observational studies and one randomized controlled trial) on acquired von Willebrand syndrome (n = 1054), and 11 observational studies on gastrointestinal bleeding (n = 300) were identified. One study reported on both associated disorders (n = 6). The pooled proportion of Heyde patients with acquired von Willebrand syndrome recovery was 86% (95% CI, 79%-91%) at T1, 90% (74%-96%) at T2, 92% (84%-96%) at T3, and 87% (67%-96%) at T4. The pooled proportion of Heyde patients with gastrointestinal bleeding cessation was 73% (62%-81%). Residual aortic valve disease was associated with lower recovery rates of acquired von Willebrand syndrome (RR 0.20; 0.05-0.72; P = 0.014) and gastrointestinal bleeding (RR 0.57; 0.40-0.81; P = 0.002). CONCLUSION: Aortic valve replacement is associated with rapid recovery of the bleeding diathesis in Heyde syndrome and gastrointestinal bleeding cessation. Residual valve disease compromises clinical benefits.

Item does not contain fulltext, AIMS: Left ventricular (LV) blood flow is determined by intraventricular pressure gradients (IVPG). Changes in blood flow initiate remodelling and precede functional decline. Novel cardiac magnetic resonance (CMR) post-processing LV-IVPG analysis might provide a sensitive marker of LV function in dilated cardiomyopathy (DCM). Therefore, the aim of our study was to evaluate LV-IVPG patterns and their prognostic value in DCM. METHODS AND RESULTS: LV-IVPGs between apex and base were measured on standard CMR cine images in DCM patients (n = 447) from the Maastricht Cardiomyopathy registry. Major adverse cardiovascular events, including heart failure hospitalisations, life-threatening arrhythmias, and sudden/cardiac death, occurred in 66 DCM patients (15%). A temporary LV-IVPG reversal during systolic-diastolic transition, leading to a prolonged transition period or slower filling, was present in 168 patients (38%). In 14%, this led to a reversal of blood flow, which predicted outcome corrected for univariable predictors [hazard ratio (HR) = 2.57, 95% confidence interval (1.01-6.51), P = 0.047]. In patients without pressure reversal (n = 279), impaired overall LV-IVPG [HR = 0.91 (0.83-0.99), P = 0.033], systolic ejection force [HR = 0.91 (0.86-0.96), P < 0.001], and E-wave decelerative force [HR = 0.83 (0.73-0.94), P = 0.003] predicted outcome, independent of known predictors (age, sex, New York Heart Association class ≥ 3, LV ejection fraction, late gadolinium enhancement, LV-longitudinal strain, left atrium (LA) volume-index, and LA-conduit strain). CONCLUSION: Pressure reversal during systolic-diastolic transition was observed in one-third of DCM patients, and reversal of blood flow direction predicted worse outcome. In the absence of pressure reversal, lower systolic ejection force, E-wave decelerative force (end of passive LV filling), and overall LV-IVPG are powerful predictors of outcome, independent of clinical and imaging parameters.

Contains fulltext : 294983.pdf (Publisher’s version ) (Open Access), An increasing number of patients develop an atherothrombotic myocardial infarction (MI) in the absence of standard modifiable risk factors (SMuRFs). Monocytes and macrophages regulate the development of atherosclerosis, and monocytes can adopt a long-term hyperinflammatory phenotype by epigenetic reprogramming, which can contribute to atherogenesis (called "trained immunity"). We assessed circulating monocyte phenotype and function and specific histone marks associated with trained immunity in SMuRFless patients with MI and matched healthy controls. Even in the absence of systemic inflammation, monocytes from SMuRFless patients with MI had an increased overall cytokine production capacity, with the strongest difference for LPS-induced interleukin-10 production, which was associated with an enrichment of the permissive histone marker H3K4me3 at the promoter region. Considering the lack of intervenable risk factors in these patients, trained immunity could be a promising target for future therapy.

Item does not contain fulltext, PURPOSE: Acute myocardial ischaemia triggers a non-specific inflammatory response of remote myocardium through the increase of plasma concentrations of acute-phase proteins, which causes myocardial oedema. As ticagrelor has been shown to significantly decrease circulating levels of several pro-inflammatory cytokines in patients after acute myocardial infarction with ST-elevation (STEMI), we sought to investigate a potential suppressive effect of ticagrelor over prasugrel on cardiac magnetic resonance (CMR) T1 and T2 values in remote myocardium. METHODS: Ninety STEMI patients were prospectively included and randomised to receive either ticagrelor or prasugrel maintenance treatment after successful primary percutaneous coronary intervention. Patients underwent CMR after 2-7 days. The protocol included long and short axis cine imaging, T1 mapping, T2 mapping and late gadolinium enhancement imaging. RESULTS: After excluding 30 patients due to either missing images or insufficient quality of the T1 or T2 maps, 60 patients were included in our analysis. Of those, 29 patients were randomised to the ticagrelor group and 31 patients to the prasugrel group. In the remote myocardium, T1 values did not differ between groups (931.3 [919.4-950.4] ms for ticagrelor vs. 932.6 [915.5-949.2] ms for prasugrel (p = 0.94)), nor did the T2 values (53.8 ± 4.6 ms for ticagrelor vs. 53.7 ± 4.7 ms for prasugrel (p = 0.86)). Also, in the infarcted myocardium, T1 and T2 values did not differ between groups. CONCLUSION: In revascularised STEMI patients, ticagrelor maintenance therapy did not show superiority over prasugrel in preventing early remote myocardial inflammation as assessed by CMR T1 and T2 mapping.

Contains fulltext : 299964.pdf (Publisher’s version ) (Open Access), OBJECTIVE: Prehospital rule-out of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) in low-risk patient with a point-of-care troponin measurement reduces healthcare costs with similar safety to standard transfer to the hospital. Risk stratification is performed identical for men and women, despite important differences in clinical presentation, risk factors and age between men and women with NSTE-ACS. Our aim was to compare safety and healthcare costs between men and women in prehospital identified low-risk patients with suspected NSTE-ACS. METHODS: In the Acute Rule-out of non-ST-segment elevation acute coronary syndrome in the (pre)hospital setting by HEART (History, ECG, Age, Risk factors and Troponin) score assessment and a single poInt of CAre troponin randomised trial, the HEAR (History, ECG, Age and Risk factors) score was assessed by ambulance paramedics in suspected NSTE-ACS patients. Low-risk patients (HEAR score ≤3) were included. In this substudy, men and women were compared. Primary endpoint was 30-day major adverse cardiac events (MACE), secondary endpoints were 30-day healthcare costs and the scores for the HEAR score components. RESULTS: A total of 863 patients were included, of which 495 (57.4%) were women. Follow-up was completed in all patients. In the total population, MACE occurred in 6.8% of the men and 1.6% of the women (risk ratio (RR) 4.2 (95% CI 1.9 to 9.2, p<0.001)). In patients with ruled-out ACS (97% of the total population), MACE occurred in 1.4% of the men and in 0.2% of the women (RR 7.0 (95% CI 2.0 to 14.2, p<0.001). Mean healthcare costs were €504.55 (95% CI €242.22 to €766.87, p<0.001) higher in men, mainly related to MACE. CONCLUSIONS: In a prehospital population of low-risk suspected NSTE-ACS patients, 30-day incidence of MACE and MACE-related healthcare costs were significantly higher in men than in women. TRIAL REGISTRATION NUMBER: NCT05466591.

Contains fulltext : 300132.pdf (Publisher’s version ) (Open Access), BACKGROUND: P2Y12 inhibitor monotherapy is a promising novel strategy to reduce bleeding complications compared to dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI). In order to personalise treatment with DAPT based on patients' bleeding risk, we compared outcomes after PCI between P2Y12 inhibitor monotherapy and DAPT according to bleeding risk. METHODS: A search for randomized clinical trials (RCTs) comparing P2Y12 inhibitor monotherapy after a short period of DAPT to standard DAPT after PCI was performed. Outcome differences between treatment groups regarding major bleedings, major adverse cardiac and cerebral events (MACCE) and net adverse clinical events (NACE) were assessed with hazard ratios (HRs) and corresponding credible intervals (CrI) according a Bayesian random effects model in patients with and without high bleeding risk (HBR). RESULTS: Five RCTs including 30,084 patients were selected. P2Y12 inhibitor monotherapy compared to DAPT reduced major bleedings in the total population (HR: 0.65, 95 % CrI: 0.44 to 0.92). The HRs of the HBR and non-HBR subgroups showed a similar reduction of bleedings for monotherapy (HBR: HR 0.66, 95 % CrI: 0.25 to 1.74; non-HBR: HR 0.63, 95 % CrI: 0.36 to 1.09). No notable differences between treatments on MACCE and NACE were observed in either sub-group or in the total population. CONCLUSIONS: Regardless of bleeding risk, P2Y12 inhibitor monotherapy is the favourable choice after PCI regarding major bleedings and does not increase ischemic events compared to DAPT. This suggests that bleeding risk is not decisive when considering P2Y12 inhibitor monotherapy.

Contains fulltext : 299992.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 299607.pdf (Publisher’s version ) (Closed access), Ideally, causal research questions will be answered with randomized trials, but this is not always feasible for practical, ethical, or methodological reasons. To obtain a reliable answer to causal questions with observational data, target trial emulation has been introduced, in which an observational study is designed, conducted, and analyzed emulating the target trial. After phrasing a causal question, this framework first addresses seven components of the target trial protocol: eligibility criteria, treatment strategies, assignment procedures, follow-up period, outcome of interest, causal contrast of interest, and statistical analysis plan. Subsequently, these elements are emulated in the observational study. This approach addresses methodological pitfalls before initiating the study, draws more unambiguous conclusions, and provides a structured assessment of limitations of observational studies as well as randomized trials. The use of the target trial framework to support the design of observational studies is increasing.

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Item does not contain fulltext, INTRODUCTION: Right ventricular (RV) function is of particular importance in systemic sclerosis (SSc), since common SSc complications, such as interstitial lung disease and pulmonary hypertension may affect RV afterload. Cardiovascular magnetic resonance (CMR) is the gold standard for measuring RV function. CMR-derived RV and right atrial (RA) strain is a promising tool to detect subtle changes in RV function, and might have incremental value, however, prognostic data is lacking. Therefore, the aim of this study was to evaluate the prognostic value of RA and RV strain in SSc. METHODS: In this retrospective study, performed at two Dutch hospitals, consecutive SSc patients who underwent CMR were included. RV longitudinal strain (LS) and RA strain were measured. Unadjusted cox proportional hazard regression analysis and likelihood ratio tests were used to evaluate the association and incremental value of strain parameters with all-cause mortality. RESULTS: A total of 100 patients (median age 54 [46-64] years, 42% male) were included. Twenty-four patients (24%) died during a follow-up of 3.1 [1.8-5.2] years. RA reservoir [Hazard Ratio (HR) = 0.95, 95% CI 0.91-0.99, p = 0.009] and conduit strain (HR = 0.93, 95% CI 0.88-0.98, p = 0.008) were univariable predictors of all-cause mortality, while RV LS and RA booster strain were not. RA conduit strain proved to be of incremental value to sex, atrial fibrillation, NYHA class, RA maximum volume indexed, and late gadolinium enhancement (p < 0.05 for all). CONCLUSION: RA reservoir and conduit strain are predictors of all-cause mortality in SSc patients, whereas RV LS is not. In addition, RA conduit strain showed incremental prognostic value to all evaluated clinical and imaging parameters. Therefore, RA conduit strain may be a useful prognostic marker in SSc patients.

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Item does not contain fulltext, We aimed to investigate BMI-z course in patients with Duchenne muscular dystrophy (DMD) during transition to loss of ambulation, and to explore the contribution of caloric intake and corticosteroid use. A retrospective multicenter longitudinal study was conducted. First, analyses of characteristics at first visit were carried out. Second, discontinuous change models were fitted to explore associations between BMI-z, loss of ambulation, caloric intake and corticosteroid use. 790 visits of 159 patients were collected. Cross sectional first visit analyses showed the presence of overweight and obesity was 44% in the ambulant group and 51% in the non-ambulant group. In the non-ambulatory group, exceeding the recommended caloric intake was associated with higher BMI-z scores (r 0.36, p = 0.04). Patients who were using corticosteroids had significantly higher BMI-z scores compared with patients not using corticosteroids (1.06 and 0.51 respectively, p = 0.02). Longitudinal analyses on patients ambulant at first visit showed an increase in BMI-z score during transition to the non-ambulatory phase. Caloric intake and corticosteroid use were not associated with BMI-z. Transition to the non-ambulatory phase may be crucial in the development of excessive weight gain. Early measures - starting before this time frame - may contribute to reduce development of obesity.

Item does not contain fulltext, AIMS: Precapillary pulmonary hypertension (pPH) affects left ventricular (LV) function by ventricular interdependence. Since LV ejection fraction (EF) is commonly preserved, LV dysfunction should be assessed with more sensitive techniques. Left atrial (LA) strain and estimation of LV intraventricular pressure gradients (IVPG) may be valuable in detecting subtle changes in LV mechanics; however, the value of these techniques in pPH is unknown. Therefore, the aim of our study is to evaluate LA strain and LV-IVPGs from cardiovascular magnetic resonance (CMR) cines in pPH patients. METHODS AND RESULTS: In this cross-sectional study, 31 pPH patients and 22 healthy volunteers underwent CMR imaging. Feature-tracking LA strain was measured on four- and two-chamber cines. LV-IVPGs (from apex-base) are computed from a formulation using the myocardial movement and velocity of the reconstructed 3D-LV (derived from long-axis cines using feature-tracking). Systolic function, both LV EF and systolic ejection IVPG, was preserved in pPH patients. Compared to healthy volunteers, diastolic function was impaired in pPH patients, depicted by (i) lower LA reservoir (36 ± 7% vs. 26 ± 9%, P < 0.001) and conduit strain (26 ± 6% vs. 15 ± 8%, P < 0.001) and (ii) impaired diastolic suction (-9.1 ± 3.0 vs. ‒6.4 ± 4.4, P = 0.02) and E-wave decelerative IVPG (8.9 ± 2.6 vs. 5.7 ± 3.1, P < 0.001). Additionally, 11 pPH patients (35%) showed reversal of IVPG at systolic-diastolic transition compared to none of the healthy volunteers (P = 0.002). CONCLUSIONS: pPH impacts LV function by altering diastolic function, demonstrated by an impairment of LA phasic function and LV-IVPG analysis. These parameters could therefore potentially be used as early markers for LV functional decline in pPH patients.

Contains fulltext : 251752.pdf (Publisher’s version ) (Open Access), BACKGROUND: In patients with primary mitochondrial disease (MD), screening with electrocardiogram (ECG) and transthoracic echocardiography (TTE) is warranted according to current guidelines as structural cardiac abnormalities are frequent. This study aims to evaluate the cardiac phenotype of a large Dutch cohort of patients with MD and investigates whether ECG alone is sufficient for predicting structural cardiac abnormalities on TTE. METHODS: In this retrospective cohort study, genetically confirmed MD patients >18 years old with an available ECG and TTE were included. Newcastle Mitochondrial Disease Scale for Adults (NMDAS) scores were assessed. ECG's were evaluated for rhythm and conduction disorders, voltage criteria for left ventricular hypertrophy (LVH) and repolarization disorders. Echocardiographic evaluation included left and right ventricular volumes and function, and presence of LVH or concentric remodeling. RESULTS: In total, 200 MD patients were included with a median age of 45 years (IQR; 37-57) of whom 36% were male. Of all MD patients, 35% had abnormalities on ECG and 61% on TTE. Most frequent structural cardiac abnormalities on TTE were: global longitudinal strain > - 18% (54%), concentric remodeling (27%) and left ventricular (LV) ejection fraction <52% (14%). Patients with maternally inherited diabetes and deafness (MIDD) and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) had the highest prevalence of ECG abnormalities (50% and 47%). TTE abnormalities were most prevalent in patients with MIDD (75%), followed by mitochondrial myopathy (MM) (55%), MELAS (47%) and Mitochondrial Epilepsy and Ragged Red Fibers (MERRF) (47%). MD patients with a high disease severity (NMDAS ≥21) had a higher prevalence of ECG abnormalities (44%, p = 0.039) and structural cardiac abnormalities (72%, p = 0.004) compared to patients with a NMDAS score of 11-20 and ≤ 10 (ECG: 34% and 19%; TTE: 63% and 39%). ECG abnormalities had a positive

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Item does not contain fulltext, AIMS: To investigate the association between the timing of cardiac surgery during pregnancy and both maternal and foetal outcomes. METHODS AND RESULTS: Studies published up to 6 February 2021 on maternal and/or foetal mortality after cardiac surgery during pregnancy that included individual patient data were identified. Maternal and foetal mortality was analysed per trimester for the total population and stratified for patients who underwent caesarean section (CS) prior to cardiac surgery (Caesarean section (CaeSe) group) vs. patients who did not (Cardiac surgery (CarSu) group). Multivariable logistic regression analysis was performed to evaluate predictors of both maternal and foetal mortality. In total, 179 studies were identified including 386 patients of which 120 underwent CS prior to cardiac surgery. Maternal mortality was 7.3% and did not differ significantly among trimesters of pregnancy (P = 0.292) nor between subgroup CaeSe and CarSu (P = 0.671). Overall foetal mortality was 26.5% and was lowest when cardiac surgery was performed during the third trimester (10.3%, P < 0.01). CS prior to surgery was significantly associated with a reduced risk of foetal mortality in a multivariable model [odds ratio 0.19, 95% confidence interval [0.06-0.56)]. Trimester was not identified as an independent predictor for foetal nor maternal mortality. CONCLUSION: Maternal mortality after cardiac surgery during pregnancy is not associated with the trimester of pregnancy. Cardiac surgery is associated with high foetal mortality but is significantly lower in women where CS is performed prior to cardiac surgery. When the foetus is viable, CS prior to cardiac surgery might be safe. When CS is not feasible, trimester stage does not seem to influence foetal mortality.

Contains fulltext : 232623.pdf (Publisher’s version ) (Open Access), BACKGROUND: There is substantial scope for enhancing population health through increased park visits and active use of parks; however, a better understanding of factors that influence park visitation is needed. This cross-sectional study examined how parent-reported satisfaction and perceived availability of parks were associated with adults' physical activity and children's physical activity and time spent outdoors, and whether these associations were mediated by park visitation. METHODS: Self-reported surveys were completed by adults living within 5 km of two parks located in Melbourne, Australia. Participants reported their satisfaction with neighbourhood park quality, walking duration from home to the nearest park, and park visitation in the past 7 days. Participants with a child aged 2-15 years also answered similar questions in relation to their child. The primary outcome variable for adults was leisure-time physical activity (LTPA) and for children was proxy-reported time spent outside. The secondary outcome for adults was combined transportation and LTPA and for children (5-15 years) was the number of days physical activity recommendations were met in the past 7 days. RESULTS: Significant positive associations between park availability and park visitation in the past 7 days, and between park visitation and the outcome variables were observed among both adults (n = 1085, M(age) = 48.9, SD 13.4) and children (n = 753, M(age) = 8.8, SD = 3.7). The association between park satisfaction and park visitation was only significant among adults. Park visitation mediated associations between park availability and park satisfaction and the outcome variables among both adults and children. CONCLUSIONS: Improving park availability and users' satisfaction with parks may increase visitation and consequently increase physical activity and time spent outdoors.

Item does not contain fulltext, Semi-continuous variables are characterized by a point mass at one value and a continuous range of values for remaining observations. An example is alcohol consumption quantity, with a spike of zeros representing non-drinkers and positive values for drinkers. If multiple imputation is used to handle missing values for semi-continuous variables, it is unclear how this should be implemented within the standard approaches of fully conditional specification (FCS) and multivariate normal imputation (MVNI). This question is brought into focus by the use of categorized versions of semi-continuous exposure variables in analyses (eg, no drinking, drinking below binge level, binge drinking, heavy binge drinking), raising the question of how best to achieve congeniality between imputation and analysis models. We performed a simulation study comparing nine approaches for imputing semi-continuous exposures requiring categorization for analysis. Three methods imputed the categories directly: ordinal logistic regression, and imputation of binary indicator variables representing the categories using MVNI (with two variants). Six methods (predictive mean matching, zero-inflated binomial imputation, and two-part imputation methods with variants in FCS and MVNI) imputed the semi-continuous variable, with categories derived after imputation. The ordinal and zero-inflated binomial methods had good performance across most scenarios, while MVNI methods requiring rounding after imputation did not perform well. There were mixed results for predictive mean matching and the two-part methods, depending on whether the estimands were proportions or regression coefficients. The results highlight the need to consider the parameter of interest when selecting an imputation procedure.

Semi-continuous variables are characterized by a point mass at one value and a continuous range of values for remaining observations. An example is alcohol consumption quantity, with a spike of zeros representing non-drinkers and positive values for drinkers. If multiple imputation is used to handle missing values for semi-continuous variables, it is unclear how this should be implemented within the standard approaches of fully conditional specification (FCS) and multivariate normal imputation (MVNI). This question is brought into focus by the use of categorized versions of semi-continuous exposure variables in analyses (eg, no drinking, drinking below binge level, binge drinking, heavy binge drinking), raising the question of how best to achieve congeniality between imputation and analysis models. We performed a simulation study comparing nine approaches for imputing semi-continuous exposures requiring categorization for analysis. Three methods imputed the categories directly: ordinal logistic regression, and imputation of binary indicator variables representing the categories using MVNI (with two variants). Six methods (predictive mean matching, zero-inflated binomial imputation, and two-part imputation methods with variants in FCS and MVNI) imputed the semi-continuous variable, with categories derived after imputation. The ordinal and zero-inflated binomial methods had good performance across most scenarios, while MVNI methods requiring rounding after imputation did not perform well. There were mixed results for predictive mean matching and the two-part methods, depending on whether the estimands were proportions or regression coefficients. The results highlight the need to consider the parameter of interest when selecting an imputation procedure.

Contains fulltext : 204018.pdf (publisher's version ) (Open Access)

Item does not contain fulltext, BACKGROUND AND PURPOSE: We externally validated a previously established multivariable normal-tissue complication probability (NTCP) model for Grade >/=2 acute esophageal toxicity (AET) after intensity-modulated (chemo-)radiotherapy or volumetric-modulated arc therapy for locally advanced non-small cell lung cancer. MATERIALS AND METHODS: A total of 603 patients from five cohorts (A-E) within four different Dutch institutes were included. Using the NTCP model, containing predictors concurrent chemoradiotherapy, mean esophageal dose, gender and clinical tumor stage, the risk of Grade >/=2 AET was estimated per patient and model discrimination and (re)calibration performance were evaluated. RESULTS: Four validation cohorts (A, B, D, E) experienced higher incidence of Grade >/=2 AET compared to the training cohort (49.3-70.2% vs 35.6%; borderline significant for one cohort, highly significant for three cohorts). Cohort C experienced lower Grade >/=2 AET incidence (21.7%, p<0.001). For three cohorts (A-C), discriminative performance was similar to the training cohort (area under the curve (AUC) 0.81-0.89 vs 0.84). In the two remaining cohorts (D-E) the model showed poor discriminative power (AUC 0.64 and 0.63). Reasonable calibration performance was observed in two cohorts (A-B), and recalibration further improved performance in all three cohorts with good discrimination (A-C). Recalibration for the two poorly discriminating cohorts (D-E) did not improve performance. CONCLUSIONS: The NTCP model for AET prediction was successfully validated in three out of five patient cohorts (AUC >/=0.80). The model did not perform well in two cohorts, which included patients receiving substantially different treatment. Before applying the model in clinical practice, validation of discrimination and (re)calibration performance in a local cohort is recommended.

Item does not contain fulltext, BACKGROUND: Young adults who are not in employment, education, or training (NEET) are at risk of long-term economic disadvantage and social exclusion. Knowledge about risk factors for being NEET largely comes from cross-sectional studies of vulnerable individuals. Using data collected over a 10-year period, we examined adolescent predictors of being NEET in young adulthood. METHODS: We used data on 1938 participants from the Victorian Adolescent Health Cohort Study, a community-based longitudinal study of adolescents in Victoria, Australia. Associations between common mental disorders, disruptive behaviour, cannabis use and drinking behaviour in adolescence, and NEET status at two waves of follow-up in young adulthood (mean ages of 20.7 and 24.1 years) were investigated using logistic regression, with generalised estimating equations used to account for the repeated outcome measure. RESULTS: Overall, 8.5% of the participants were NEET at age 20.7 years and 8.2% at 24.1 years. After adjusting for potential confounders, we found evidence of increased risk of being NEET among frequent adolescent cannabis users [adjusted odds ratio (ORadj) = 1.74; 95% confidence interval (CI) 1.10-2.75] and those who reported repeated disruptive behaviours (ORadj = 1.71; 95% CI 1.15-2.55) or persistent common mental disorders in adolescence (ORadj = 1.60; 95% CI 1.07-2.40). Similar associations were present when participants with children were included in the same category as those in employment, education, or training. CONCLUSIONS: Young people with an early onset of mental health and behavioural problems are at risk of failing to make the transition from school to employment. This finding reinforces the importance of integrated employment and mental health support programmes.

Contains fulltext : 181915.pdf (publisher's version ) (Open Access), Preterm infants often have a reduced bone mineral content (BMC) with increased risk of metabolic bone disease. After birth it is difficult to supply calcium (Ca) and phosphorus (P) comparable to the high fetal accretion rate. It is not known whether high supplementation of minerals in the early postnatal period improves growth and bone mineralization. The aim of this study was to evaluate growth and bone mineralization at term corrected age (TCA) in very and extremely preterm infants who received different enteral Ca and P intakes during the first 10 days of life. Infants (n = 109) with birth weights below 1500 g were randomly assigned to one of three groups that differed in the nutritional protocols delivered until day 10: Group A, mother's own milk (MOM) and donor milk (unfortified); Group B, MOM (unfortified) and preterm formula; Group C, MOM (start fortification >50 mL/day) and preterm formula. Due to the earlier commencement of fortification, Group C received higher intakes of calcium and phosphorus and protein (p < 0.001) until day 10. At TCA weight, length, BMC and bone mineral density (BMD), measured by dual-X-ray absorptiometry, were not different between the groups. Nutritional intake of P was positively associated with length (beta; (95% confidence interval (CI): 0.20 (0.001; 0.393); p-value = 0.048), whereas Ca intake was negatively associated with BMC (-1.94 (-2.78; -1.09); p-value < 0.001). A small interaction between Ca and P intake was only found for BMD (0.003 (0.00002; 0.00006); p-value = 0.036). The volume of human milk per kg provided during the first 10 days was positively associated with BMC (beta; (95% CI): 0.013 (0.002; 0.023); p < 0.017). Higher intakes of Ca and P during the first 10 days, as provided in this study, did not improve bone mineralization at term corrected age.