Effect of bariatric surgery on NAFLD/NASH: a single-centre observational prospective cohort study.

INTRODUCTION: The prevalence of non-alcoholic fatty liver disease (NAFLD) ranges from 25% in the general population to 90% in patients with obesity scheduled for bariatric surgery. NAFLD can progress towards non-alcoholic steatohepatitis (NASH) associated with complications such as cirrhosis, hepatocellular carcinoma and cardiovascular disease. To date, losing weight and lifestyle modifications are the best known treatments for NASH. Bariatric surgery significantly improves NAFLD/NASH in the short term. However, the extent of this improvement is not yet clear and long-term data on the natural course of NAFLD/NASH after bariatric surgery are lacking. The factors involved in NAFLD/NASH regression after bariatric surgery have not been elucidated. METHODS AND ANALYSIS: This is an observational prospective cohort study including patients scheduled for bariatric surgery. Extensive metabolic and cardiovascular analyses will be carried out including measurements of carotid intima media thickness and pulse wave velocity. Genomic, proteomic, lipidomic and metabolomic studies will be done. Microbioma analyses before and 1 year after surgery will be done. Transient elastography measurements will be performed before and at 1, 3 and 5 years after surgery. For those with an elevated preoperative transient elastography measurement by Fibroscan, a laparoscopic liver biopsy will be performed during surgery. Primary outcome measures are the change of steatosis and liver fibrosis 5 years after surgery. Secondary outcome measure is the comparison of the transient elastography measurements with the NAFLD Activity Score from the biopsies. ETHICS AND DISSEMINATION: The protocol has been approved by the Medical Research Ethics Committees United, Nieuwegein, on 1 March 2022 (registration code R21.103/NL79423.100.21). The study results will be submitted for publication in peer-reviewed journals and data will be presented at scientific meetings. TRIAL REGISTRATION NUMBER: NCT05499949.

Normalization of Cardiac Function After Bariatric Surgery Is Related to Autonomic Function and Vitamin D.

PURPOSE: Subclinical cardiac dysfunction is common in patients with obesity. Bariatric surgery is associated with normalization of subclinical cardiac function in 50% of the patients with obesity. The aim of this study was to identify predictors for a lack of improvement of subclinical cardiac dysfunction 1-year post-bariatric surgery. METHODS: Patients who were referred for bariatric surgery were enrolled in a longitudinal study. Inclusion criteria were age 35-65 years and BMI ≥ 35 kg/m2. Patients with a suspicion of or known cardiovascular disease were excluded. Conventional and advanced echocardiography, Holter monitoring, and blood tests were performed pre- and 1-year post-bariatric surgery. Subclinical cardiac dysfunction was defined as either a reduced left ventricular ejection fraction, decreased global longitudinal strain (GLS), diastolic dysfunction, arrhythmia, or an increased BNP or hs Troponin I. RESULTS: A total of 99 patients were included of whom 59 patients had cardiac dysfunction at baseline. Seventy-two patients completed the 1-year follow-up after bariatric surgery. There was a significant reduction in weight and cardiovascular risk factors. Parameters of cardiac function, such as GLS, improved. However, in 20 patients cardiac dysfunction persisted. Multivariate analysis identified a decreased heart rate variability (which is a measure of autonomic function), and a decreased vitamin D pre-surgery as predictors for subclinical cardiac dysfunction after bariatric surgery. CONCLUSION: Although there was an overall improvement of cardiac function 1-year post-bariatric surgery, autonomic dysfunction and a decreased vitamin D pre-bariatric surgery were predictors for a lack of improvement of subclinical cardiac dysfunction.

Evaluation of nonalcoholic fatty liver disease (NAFLD) in severe obesity using noninvasive tests and imaging techniques.

The prevalence of nonalcoholic fatty liver disease (NAFLD) and the more severe and inflammatory type, nonalcoholic steatohepatitis (NASH), is increasing rapidly. Especially in high-risk patients, that is those with obesity, metabolic syndrome, and type 2 diabetes mellitus, the prevalence of NAFLD can be as high as 80% while NASH may be present in 20% of these subjects. With the worldwide increase of obesity, it is most likely that these numbers will rise. Since advanced stages of NAFLD and NASH are strongly associated with morbidity and mortality-in particular, cardiovascular disease, liver cirrhosis, and hepatocellular carcinoma-it is of great importance to identify subjects at risk. A great variety of noninvasive tests has been published to diagnose NAFLD and NASH, especially using blood- and imaging-based tests. Liver biopsy remains the gold standard for NAFLD/NASH. This review aims to summarize the different mechanisms leading to NASH and liver fibrosis, the different noninvasive liver tests to diagnose and evaluate patients with severe obesity.

Correlation and Relative Prognostic Value of Fractional Flow Reserve and Pd/Pa of Nonculprit Lesions in ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: The applicability of resting indices to guide noninfarct-related artery revascularization in ST-elevation myocardial infarction is unknown. METHODS: We analyzed the correlation and prognostic value of fractional flow reserve (FFR) and resting distal coronary to aortic pressure ratio (Pd/Pa) in all patients of the Compare-Acute trial in whom, after successful primary percutaneous coronary intervention, the noninfarct-related artery was interrogated by both and treated medically. The treating cardiologist was blinded to these values. The primary end point was the composite of target vessel (interrogated noninfarct-related artery) related nonfatal target vessel myocardial infarction and target vessel repeat revascularization at 36 months. RESULTS: Five hundred seventeen patients (665 vessels) were included. On receiver-operating characteristic analysis, the optimal Pd/Pa cut off for FFR≤0.80 was 0.905 (C statistic: 0.894). The diagnostic accuracy of Pd/Pa was 80.15% (95% CI, 76.91%-83.12%) with respect to FFR. During the 36-month follow-up, 130 target vessel revascularization and 14 target vessel myocardial infarction occurred. FFR and Pd/Pa had a diagnostic accuracy to predict these events of 62.86% (95% CI, 59.06%-66.54%) and 56.84% (95% CI, 52.98%-60.64%), respectively (P=0.20). When they were discrepant, FFR was significantly better than Pd/Pa in identifying which vessels could be safely deferred (P=0.048). CONCLUSIONS: Immediately after successful primary percutaneous coronary intervention, resting Pd/Pa has a diagnostic accuracy of 80% with respect to FFR measured in the noninfarct-related artery. FFR is not significantly superior in predicting target vessel myocardial infarction and target vessel revascularization during 36 months of follow-up but, in case FFR and Pd/Pa are discrepant, FFR is superior in identifying which nonculprit vessels can be safely deferred. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01399736.

Adult but not childhood onset asthma is associated with the metabolic syndrome, independent from body mass index.

INTRODUCTION: Adult-onset asthma (AOA) is usually more severe compared to childhood onset asthma (CoA). Given the increasing evidence that AoA is associated with obesity, we investigated the relationship of other related metabolic comorbid conditions with AoA compared to CoA. STUDY DESIGN AND METHODS: This cross-sectional study compared the metabolic syndrome and lipid derived inflammatory markers in patients with AoA, CoA and age- and sex-matched control subjects without asthma. Participants were asthma patients visiting the outpatient clinic of two teaching hospitals in Rotterdam, The Netherlands. All participants underwent lung function tests, blood tests and physical activity tracking. AoA was defined as asthma age of onset after the age of 18 years. Metabolic syndrome was defined according to the international joint interim statement criteria. RESULTS: Eighty-one participants were included (27 AoA, 25 CoA, 29 controls). AoA was associated with the metabolic syndrome (Odds Ratio = 3.64 95% CI (1.16-11.42) p = 0.03, Nagelkerke R2 = 0.26), adjusted for age, sex, body mass index and smoking habits. AoA patients had higher median serum IL-6 and leptin-adiponectin (LA) ratio compared to controls (IL-6 (pg/mL): 3.10 [1.11-4.30] vs. 1.13 [0.72-1.58], p = 0.002 and LA ratio (pg/mL): 6.21 [2.45-14.11] vs. 2.24 [0.67-4.71], p = 0.0390). This was not observed in CoA and controls. CONCLUSION: AoA was associated with the metabolic syndrome and its related pro-inflammatory endocrine and cytokine status. This may suggest adipose tissue derived inflammatory markers play a role in the pathophysiology of AoA.

Psychological distress and health-related quality of life in patients after hospitalization during the COVID-19 pandemic: A single-center, observational study.

INTRODUCTION: Illnesses requiring hospitalization are known to negatively impact psychological well-being and health-related quality of life (HRQoL) after discharge. The impact of hospitalization during the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) pandemic on psychological well-being and health-related quality of life is expected to be higher due to the exceptional circumstances within and outside the hospital during the pandemic surge. The objective of this study was to quantify psychological distress up to three months after discharge in patients hospitalized during the first coronavirus disease 2019 (COVID-19) pandemic wave. We also aimed to determine HRQoL, to explore predictors for psychological distress and HRQoL, and to examine whether psychological distress was higher in COVID-19 confirmed patients, and in those treated in Intensive Care Units (ICUs). METHODS: In this single-center, observational cohort study, adult patients hospitalized with symptoms suggestive of COVID-19 between March 16 and April 28, 2020, were enrolled. Patients were stratified in analyses based on SARS-CoV-2 PCR results and the necessity for ICU treatment. The primary outcome was psychological distress, expressed as symptoms of post-traumatic stress disorder (PTSD), anxiety, and depression, up to three months post-discharge. Health-related quality of life (HRQoL) was the secondary outcome. Exploratory outcomes comprised predictors for psychological distress and HRQoL. RESULTS: 294 of 622 eligible patients participated in this study (median age 64 years, 36% female). 16% and 13% of these patients reported probable PTSD, 29% and 20% probable anxiety, and 32% and 24% probabledepression at one and three months after hospital discharge, respectively. ICU patients reported less frequently probable depression, but no differences were found in PTSD, anxiety, or overall HRQoL. COVID-19 patients had a worse physical quality of life one month after discharge, and ICU patients reported a better mental quality of life three months after discharge. PTSD severity was predicted by time after discharge and being Caucasian. Severity of anxiety was predicted by time after discharge and being Caucasian. Depression severity was predicted by time after discharge and educational level. CONCLUSION: COVID-19 suspected patients hospitalized during the pandemic frequently suffer from psychological distress and poor health-related quality of life after hospital discharge. Non-COVID-19 and non-ICU patients appear to be at least as affected as COVID-19 and ICU patients, underscoring that (post-)hospital pandemic care should not predominantly focus on COVID-19 infected patients.

Bacterial lysate add-on therapy to reduce exacerbations in severe asthma: A double-blind placebo-controlled trial.

BACKGROUND: Asthma exacerbations are frequently induced by respiratory tract infections (RTIs). Bacterial lysates have been described to possess immune-modulatory effects and reduce RTIs as well as asthma symptoms in children. However, whether bacterial lysates have similar effects in adult asthma patients is unknown. AIMS: To reduce asthma exacerbations by add-on bacterial lysate therapy in adults with severe asthma and to characterize the clinical and immune-modulatory effects of this treatment. METHODS: Asthma patients (GINA 4) with ≥2 annual exacerbations in the previous year were included. The intervention regimen consisted of OM-85/placebo for 10 consecutive days per month for 6 months during two winter seasons. Primary end-point was the number of severe asthma exacerbations within 18 months. The study was approved by the national and local ethical review board and registered in the Dutch Trial Registry (NL5752). All participants provided written informed consent. RESULTS: Seventy-five participants were included (38 OM-85; 37 placebo). Exacerbation frequencies were not different between the groups after 18 months (incidence rate ratio 1.07, 95%CI [0.68-1.69], p = 0.77). With the use of OM-85, FEV1% increased by 3.81% (p = 0.04) compared with placebo. Nasopharyngeal swabs taken during RTIs detected a virus less frequently in patients using OM-85 compared to placebo (30.5% vs. 48.0%, p = 0.02). In subjects with type 2 inflammation adherent to the protocol (22 OM-85; 20 placebo), a non-statistically significant decrease in exacerbations in the OM-85 group was observed (IRR = 0.71, 95%CI [0.39-1.26], p = 0.25). Immune-modulatory effects included an increase in several plasma cytokines in the OM-85 group, especially IL-10 and interferons. Peripheral blood T- and B cell subtyping, including regulatory T cells, did not show differences between the groups. CONCLUSION: Although OM-85 may have immune-modulatory effects, it did not reduce asthma exacerbations in this heterogeneous severe adult asthma group. Post hoc analysis showed a potential clinical benefit in patients with type 2 inflammation.

SARS-CoV-2 antibody response dynamics and heterogeneous diagnostic performance of four serological tests and a neutralization test in symptomatic healthcare workers with non-severe COVID-19.

BACKGROUND: Most COVID-19 patients experience non-severe illness. The presence of SARS-CoV-2 antibodies suggest possible protection against re-infections in prior SARS-CoV-2 infected individuals. OBJECTIVES: The aims of this prospective observational study were to longitudinally assess the antibody response during the first 4-6 months after polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection, and to study the diagnostic performance of four different enzyme-linked immunosorbent assays (ELISAs) and a surrogate virus neutralization test (sVNT) in symptomatic healthcare workers (HCWs) with non-severe COVID-19. STUDY DESIGN: HCWs in a teaching hospital were included between March 8 and June 15, 2020, when they had a PCR-confirmed SARS-CoV-2 infection in the past 3 months. The performances of four ELISAs (Wantai, Bio-Rad Platelia, BioTrading Immy clarus, and Euroimmun) were evaluated in serum samples obtained at the moment of study inclusion and subsequently at 1, 2 and 3 months thereafter. Furthermore, in the last available serum sample sVNT by GenScript was performed. RESULTS: 309 samples from 80 positive HCWs were included of whom 70 (88%) were SARS-CoV-2 seropositive. The detection rates of SARS-CoV-2 antibodies by the different ELISAs were heterogenous ranging from 64% for the Euroimmun ELISA to 88% for the Wantai ELISA. The Wantai ELISA had the highest and almost perfect agreement with sVNT (96%, Cohen's kappa 0.83). CONCLUSION: SARS-CoV-2 (neutralizing) antibodies were detectable in most symptomatic individuals with non-severe COVID-19. The presence of antibodies remained stable up to six months after initial infection. There is large variability in diagnostic test performance between ELISA tests.

Percutaneous Coronary Intervention vs Medical Therapy for Coronary Lesions With Positive Fractional Flow Reserve (FFR) but Preserved Pressure-Bounded Coronary Flow Reserve (CFR): A Substudy of the Randomized Compare-Acute Trial.

OBJECTIVES: Performing percutaneous coronary intervention (PCI) for fractional flow reserve (FFR) positive coronary lesions improves clinical outcomes and is recommended by international guidelines. It has been hypothesized that lesions with a positive FFR but a preserved coronary flow reserve (CFR) are less likely to be flow limiting and might best be treated medically. We investigated the association of CFR in FFR-positive lesions with clinical outcomes when treated medically, as well as the treatment effect of PCI vs medical therapy in FFR-positive lesions and a preserved CFR. METHODS: We performed a substudy of the randomized, multicenter Compare-Acute trial, in which stabilized ST-segment elevation myocardial infarction (STEMI) patients with non-culprit lesions were randomized to either FFR-guided PCI or medical therapy. Based on baseline and hyperemic pressure gradients, we computed physiologic limits of CFR, the so-called pressure-bounded CFR (pb-CFR), and classified lesions as low (<2) or preserved (≥2). The primary endpoint was 12-month major adverse cardiac and cerebrovascular event (MACCE) rate, defined as a composite of death from any cause, non-fatal myocardial infarction, revascularization, or cerebrovascular events. RESULTS: A total of 980 lesions from 885 patients were included in this substudy. In lesions with FFR ≤0.80, a total of 249 patients had a pb-CFR <2 and 29 patients had a preserved CFR (pb-CFR ≥2). The rate of MACCE at 1 year was not significantly different between patients with FFR ≤0.80 and pb-CFR <2 vs patients with FFR ≤0.80 and pb-CFR ≥2 (25% vs 17%, respectively; P=.39). Because of randomization, baseline characteristics were well balanced between patients with FFR ≤0.80 and pb-CFR ≥2 treated by either by PCI or medical therapy. Importantly, in patients with FFR ≤0.80 and pb-CFR ≥2, MACCE occurred more frequently in patients treated medically vs patients treated by PCI (44% vs 0%, respectively; P=.01). CONCLUSIONS: Preserved or low pb-CFR did not alter clinical outcomes in patients with a positive FFR. Patients with FFR-positive coronary lesions but a preserved CFR had more clinical events when treated medically vs those treated with PCI.

Association between elevated serum triglycerides and asthma in patients with obesity: An explorative study.

Background: Adults with a high body mass index (BMI) have an increased risk of developing asthma. To explore the impact of increased lipids on the presence of asthma, this study investigated the relationship between lipid levels and inflammatory markers in patients with asthma and controls with obesity. Objective: We hypothesized that higher lipid levels are more prevalent in patients with obesity and asthma. Methods: In this explorative cohort study, 96 patients with asthma and 45 controls were included. All the patients participated in one of three asthma studies; two of these studies included only patients with obesity. An asthma diagnosis was defined by the presence of typical clinical symptoms, reversible airway obstruction (+12% improvement in forced expiratory volume in the first second of expiration after bronchodilator), or bronchial hyperreactivity (Histamine PC20 < 8 mg/mL), or a fractional exhaled nitric oxide of > 50 ppb. We compared lipid levels and neutrophils and eosinophils in patients with asthma and the controls with a wide BMI range (17.8-63.8 kg/m²). Multivariable logistic regression was used to analyze the data. Results: Serum triglycerides were statistically significantly higher in patients with obesity and asthma adjusted for BMI, blood eosinophils, and statin use (odds ratio [OR] 2.56 [95% confidence interval, 1.34-4.88]; p = 0.004). Inclusion or exclusion of those who used long-acting ß2-agonists and inhaled corticosteroids led to comparable adjusted ORs for blood triglyceride and blood eosinophils levels. Conclusion: Elevated serum triglycerides were associated with the presence of asthma in patients with obesity. This indicated that elevated triglycerides might be a yet unrecognized trait that contributed to the development of asthma. The precise cause and effect of these high triglyceride levels in the patients with asthma and with obesity were not determined in this study.Clinical trial Trial registration NCT03278561, www.clinicaltrials.gov; NL4262, NL3056, trialregister.nl.

Meta-Analysis Comparing Same-Sitting and Staged Percutaneous Coronary Intervention of Non-Culprit Artery for ST-Elevation Myocardial Infarction with Multivessel Coronary Disease.

Recent trials and meta-analysis have indicated that complete revascularization (CR) of multivessel coronary disease is beneficial in patients with ST-segment elevation myocardial infarction (STEMI) compared to culprit-only intervention. However, the optimal timing of CR remains unclear. We aimed to analyze the optimal timing of CR in patients with STEMI and multivessel disease by performing an updated network meta-analysis using the recent largest randomized controlled trial. PUBMED and EMBASE were searched through October 2020 to identify randomized controlled trials comparing CR and culprit-only revascularization. A random-effect network meta-analysis comparing three arms (same-sitting [during the index procedure] CR versus staged CR versus culprit-only) and 4 arms (same-sitting CR versus staged CR [in-hospital] versus staged CR [out-hospital] versus culprit-only) were performed. Eleven studies with a total of 7,015 patients were included in our analysis. There was no significant difference in major adverse cardiovascular event (MACE) (HR 0.82, 95% CI 0.64-1.05), cardiovascular death (HR 0.69, 95%CI 0.35-1.33), myocardial infarction (HR 0.66, 95%CI 0.37-1.16), and revascularization (HR 1.05, 95%CI 0.70-1.58) between same-sitting CR and staged CR. When staged CR was further divided into staged CR during the hospitalization and after discharge, there was no significant difference in these outcomes between staged CR (in-hospital) and staged CR (out-hospital). In conclusion, in patients with multivessel disease presenting with STEMI, complete revascularization at any timing, including same-sitting, staged in-hospital, and staged out-hospital, may have similar benefits.

Subclinical cardiac dysfunction in obesity patients is linked to autonomic dysfunction: findings from the CARDIOBESE study.

AIMS: Obesity doubles the lifetime risk of developing heart failure. Current knowledge on the role of obesity in causing cardiac dysfunction is insufficient for optimal risk stratification. The aim of this study was first to estimate the prevalence of subclinical cardiac dysfunction in obesity patients and second to investigate the underlying pathophysiology. METHODS AND RESULTS: The CARDIOBESE study is a cross-sectional multicentre study of 100 obesity patients [body mass index (BMI) ≥ 35 kg/m2 ] without known cardiovascular disease and 50 age-matched and gender-matched non-obese controls (BMI ≤ 30 kg/m2 ). Echocardiography was performed, blood samples were collected, and a Holter monitor was affixed. Fifty-nine obesity patients [48 (42-50) years, 70% female] showed subclinical cardiac dysfunction: 57 patients had decreased global longitudinal strain (GLS), and two patients with normal GLS had either diastolic dysfunction or increased brain natriuretic peptide (BNP). Only one non-obese control had diastolic dysfunction, and none had another sign of cardiac dysfunction. Multivariable logistic analysis identified male gender and standard deviation of all NN intervals (SDNN) index, which is a measure of autonomic dysfunction, as independent significant risk factors for subclinical cardiac dysfunction in obesity patients. CONCLUSIONS: There was a high prevalence (61%) of subclinical cardiac dysfunction in obesity patients without known cardiovascular disease, which appeared to be best identified by GLS. Subclinical cardiac dysfunction in obesity was linked to autonomic dysfunction and male gender, and not to the presence of traditional cardiac risk factors, increased C-reactive protein, increased BNP, increased high-sensitivity troponin I, or increased left ventricular mass.

Chest CT for triage during COVID-19 on the emergency department: myth or truth?

PURPOSE: We aimed to investigate the diagnostic performance of chest CT compared with first RT-PCR results in adult patients suspected of COVID-19 infection in an ED setting. We also constructed a predictive machine learning model based on chest CT and additional data to improve the diagnostic accuracy of chest CT. METHODS: This study's cohort consisted of 319 patients who underwent chest CT and RT-PCR testing at the ED. Patient characteristics, demographics, symptoms, vital signs, laboratory tests, and chest CT results (CO-RADS) were collected. With first RT-PCR as reference standard, the diagnostic performance of chest CT using the CO-RADS score was assessed. Additionally, a predictive machine learning model was constructed using logistic regression. RESULTS: Chest CT, with first RT-PCR as a reference, had a sensitivity, specificity, PPV, and NPV of 90.2%, 88.2%, 84.5%, and 92.7%, respectively. The prediction model with CO-RADS, ferritin, leucocyte count, CK, days of complaints, and diarrhea as predictors had a sensitivity, specificity, PPV, and NPV of 89.3%, 93.4%, 90.8%, and 92.3%, respectively. CONCLUSION: Chest CT, using the CO-RADS scoring system, is a sensitive and specific method that can aid in the diagnosis of COVID-19, especially if RT-PCR tests are scarce during an outbreak. Combining a predictive machine learning model could further improve the accuracy of diagnostic chest CT for COVID-19. Further candidate predictors should be analyzed to improve our model. However, RT-PCR should remain the primary standard of testing as up to 9% of RT-PCR positive patients are not diagnosed by chest CT or our machine learning model.

The Natural History of Nonculprit Lesions in STEMI: An FFR Substudy of the Compare-Acute Trial.

OBJECTIVES: The aim of this study was to determine the prognostic value of fractional flow reserve (FFR) in non-infarct-related arteries (IRAs) in ST-segment elevation myocardial infarction (MI). BACKGROUND: Patients with ST-segment elevation MI often present with multivessel disease. The treatment of non-IRAs is debated. The applicability of FFR has not been widely proved. METHODS: Outcomes were analyzed in all patients in the Compare-Acute (Comparison Between FFR Guided Revascularization Versus Conventional Strategy in Acute STEMI Patients With MVD) trial in whom, after successful primary percutaneous coronary intervention, non-IRAs were interrogated using FFR and treated medically. The treating cardiologist was blinded to the FFR value. The primary endpoint was the composite of cardiovascular mortality, target vessel-related (non-IRA with FFR measurement at primary percutaneous coronary intervention) nonfatal MI, and target vessel revascularization: major adverse cardiac events (MACE) at 24 months. RESULTS: A total of 751 patients (963 vessels) were included. Target non-IRAs with MACE had lower FFR compared with those without (0.78 vs. 0.84, respectively; p < 0.001). The median FFR of non-IRAs with TVR was lower than that of those without (0.79 vs. 0.85, respectively; p < 0.001). The difference was significant in all vessels. The median FFR of target non-IRAs with MI was lower than that of those without (0.79 vs. 0.84, respectively; p = 0.016). The MACE rate was significantly (p < 0.001) higher in the lowest of FFR tertiles (<0.80) compared with the others (0.80 to 0.87 and ≥0.88). CONCLUSIONS: In patients with ST-segment elevation MI with multivessel disease, FFR measured in the medically treated non-IRA immediately after successful primary percutaneous coronary intervention shows a nonlinear and inverse risk continuum of MACE. Importantly, worsening prognosis is demonstrated around the cutoff of 0.80.

Fractional flow reserve-guided multivessel angioplasty in myocardial infarction: three-year follow-up with cost benefit analysis of the Compare-Acute trial.

AIMS: The Compare-Acute trial showed superiority of fractional flow reserve (FFR)-guided acute complete revascularisation compared to culprit-only treatment in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) at one year. The aim of this study was to investigate the outcome at three years, together with cost analysis of this strategy. METHODS AND RESULTS: After primary percutaneous coronary intervention (PCI), 885 patients with STEMI and MVD were randomised (1:2 ratio) to FFR-guided complete revascularisation (295 patients) or infarct-related artery (IRA)-only treatment (590 patients). After 36 months, the primary endpoint (composite of death, myocardial infarction, revascularisation, stroke) occurred significantly less frequently in the FFR-guided complete revascularisation group: 46/295 patients (15.6%) versus 178/590 patients (30.2%) (HR 0.46, 95% CI: 0.33-0.64; p<0.001). This benefit was driven mainly by the reduction of revascularisations in the follow-up (12.5% vs 25.2%; HR 0.45, 95% CI: 0.31-0.64; p<0.001). Cost analysis shows benefit of the FFR-guided complete revascularisation strategy, which can reduce the cost per patient by up to 21% at one year (8,150€ vs 10,319€) and by 22% at three years (8,653€ vs 11,100€). CONCLUSIONS: In patients with STEMI and MVD, FFR-guided complete revascularisation is more beneficial in terms of outcome and healthcare costs compared to IRA-only revascularisation at 36 months.

Fractional flow reserve-guided percutaneous coronary intervention vs. medical therapy for patients with stable coronary lesions: meta-analysis of individual patient data.

Aims: To assess the effect of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) with contemporary drug-eluting stents on the composite of cardiac death or myocardial infarction (MI) vs. medical therapy in patients with stable coronary lesions. Methods and results: We performed a systematic review and meta-analysis of individual patient data (IPD) of the three available randomized trials of contemporary FFR-guided PCI vs. medical therapy for patients with stable coronary lesions: FAME 2 (NCT01132495), DANAMI-3-PRIMULTI (NCT01960933), and Compare-Acute (NCT01399736). FAME 2 enrolled patients with stable coronary artery disease (CAD), while the other two focused on non-culprit lesions in stabilized patients after acute coronary syndrome. A total of 2400 subjects were recruited from 54 sites world-wide with 1056 randomly assigned to FFR-guided PCI and 1344 to medical therapy. The pre-specified primary outcome was a composite of cardiac death or MI. We included data from extended follow-ups for FAME 2 (up to 5.5 years follow-up) and DANAMI-3-PRIMULTI (up to 4.7 years follow-up). After a median follow-up of 35 months (interquartile range 12-60 months), a reduction in the composite of cardiac death or MI was observed with FFR-guided PCI as compared with medical therapy (hazard ratio 0.72, 95% confidence interval 0.54-0.96; P = 0.02). The difference between groups was driven by MI. Conclusion: In this IPD meta-analysis of the three available randomized controlled trials to date, FFR-guided PCI resulted in a reduction of the composite of cardiac death or MI compared with medical therapy, which was driven by a decreased risk of MI.

Cross-sectional and prospective follow-up study to detect early signs of cardiac dysfunction in obesity: protocol of the CARDIOBESE study.

INTRODUCTION: In view of the increasing occurrence of both obesity and heart failure, a growing overlap of these two clinical entities in the near future is expected. Significant advances in our understanding of the pathophysiological consequences of obesity for the cardiovascular system have been made over the past two decades. However, to optimise management and treatment of obesity patients, further research is required to improve early identification of cardiac dysfunction in obesity and to gain insight in the underlying pathophysiology. The CARdiac Dysfunction In OBesity - Early Signs Evaluation (CARDIOBESE) study has been designed to address these issues. METHODS AND ANALYSIS: CARDIOBESE is a cross-sectional multicentre study of 100 obesity patients scheduled for bariatric surgery (body mass index (BMI) ≥35 kg/m2) without known cardiovascular disease, and 50 age-matched and gender-matched non-obese controls (BMI <30 kg/m2). Echocardiography, blood and urine biomarkers and Holter monitoring will be used to identify parameters that are able to show cardiac dysfunction at a very early stage in obesity patients (primary objective). Furthermore, a prospective follow-up study of obesity patients before and 1 year after bariatric surgery will be done to gain insight in the pathophysiology of obesity causing cardiac dysfunction (secondary objective). ETHICS AND DISSEMINATION: The study was approved by the Medical Ethics Committee Toetsingscommissie Wetenschappelijk Onderzoek Rotterdam e.o. (TWOR). Inclusion of patients and controls is almost complete. Analyses of the investigations are currently being performed, and dissemination through peer-reviewed publications and conference presentations is expected from the first quarter of 2019. By identifying early markers of cardiac dysfunction in obesity, and by understanding the underlying pathophysiology of the abnormalities of these markers, the CARDIOBESE study may provide guidance for risk stratification, monitoring and treatment strategies for obesity patients.

Efficacy of Hydroxychloroquine in Hand Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To determine the symptom-modifying effect of hydroxychloroquine (HCQ) in hand osteoarthritis (OA). METHODS: In this randomized, double-blind, multicenter trial, patients with symptomatic hand OA received either HCQ 400 mg once a day or placebo during 24 weeks. The primary outcome was change of pain measured on a 100-mm visual analog scale (VAS) at 24 weeks. Secondary outcomes included decrease of pain at weeks 6 and 12 and change in Australian Canadian Hand Osteoarthritis Index (AUSCAN) and Arthritis Impact Measurement Scale 2 short form (AIMS2-SF) total scores. RESULTS: A total of 196 patients was included (placebo n = 98, HCQ n = 98). Mean ± SD age was 58.0 ± 7.6 years, and 86% were female. Baseline mean ± SD pain VAS was 44.9 ± 22.9 mm in the placebo group and 43.2 ± 22.3 mm in the HCQ group. At 24 weeks, change in pain VAS was not significantly different between both groups (imputed mean VAS 42.7 in the HCQ group versus 45.3 in the placebo group after 24 weeks), as was the case in pain VAS at weeks 6 and 12. Changes in AUSCAN total score and AIMS2-SF total score in both groups were similar between the groups. In total, 24 patients in the placebo group and 21 patients in the HCQ group reported ≥1 adverse event. In the HCQ group, 3 patients reported a severe allergic reaction. Fifteen patients withdrew from the study (5 placebo, 10 HCQ group) due to adverse events. CONCLUSION: Treatment with HCQ at 24 weeks is not effective in reducing the symptoms of hand OA compared to placebo.