Contemporary guideline-directed medical therapy in de novo, chronic, and worsening heart failure patients: First data from the TITRATE-HF study.

AIMS: Despite clear guideline recommendations for initiating four drug classes in all patients with heart failure (HF) with reduced ejection fraction (HFrEF) and the availability of rapid titration schemes, information on real-world implementation lags behind. Closely following the 2021 ESC HF guidelines and 2023 focused update, the TITRATE-HF study started to prospectively investigate the use, sequencing, and titration of guideline-directed medical therapy (GDMT) in HF patients, including the identification of implementation barriers. METHODS AND RESULTS: TITRATE-HF is an ongoing long-term HF registry conducted in the Netherlands. Overall, 4288 patients from 48 hospitals were included. Among these patients, 1732 presented with de novo, 2240 with chronic, and 316 with worsening HF. The median age was 71 years (interquartile range [IQR] 63-78), 29% were female, and median ejection fraction was 35% (IQR 25-40). In total, 44% of chronic and worsening HFrEF patients were prescribed quadruple therapy. However, only 1% of HFrEF patients achieved target dose for all drug classes. In addition, quadruple therapy was more often prescribed to patients treated in a dedicated HF outpatient clinic as compared to a general cardiology outpatient clinic. In each GDMT drug class, 19% to 36% of non-use in HFrEF patients was related to side-effects, intolerances, or contraindications. In the de novo HF cohort, 49% of patients already used one or more GDMT drug classes for other indications than HF. CONCLUSION: This first analysis of the TITRATE-HF study reports relatively high use of GDMT in a contemporary HF cohort, while still showing room for improvement regarding quadruple therapy. Importantly, the use and dose of GDMT were suboptimal, with the reasons often remaining unclear. This underscores the urgency for further optimization of GDMT and implementation strategies within HF management.

Clinical outcomes after primary repair for thumb ulnar collateral ligament ruptures: a systematic review and meta-analysis.

There is no consensus on the best surgical technique for treating thumb ulnar collateral ligament (UCL) ruptures. This systematic review and meta-analysis investigates which primary repair technique and postoperative immobilization protocol result in the best clinical outcomes. A literature search was conducted in Embase, Medline ALL Ovid, Web of Science Core Selection and Cochrane Central Register of Controlled Trials. Pain, stability, tip pinch strength, key pinch strength, grip strength, return to work and metacarpophalangeal joint range of motion were collected as postoperative outcomes. In total, 29 studies were included. All surgical techniques resulted in satisfactory clinical outcomes, with no significant differences between bone anchor reinsertion, suture fixation, K-wire fixation and a combination of techniques. K-wire immobilization resulted in worse postoperative pain, but similar stability compared to immobilization without a K-wire. Clinical outcomes after thumb UCL repair are excellent, with no differences in clinical outcomes noted among surgical techniques.

Pulmonary Computed Tomography Screening Frequency in Primary Antibody Deficiency.

BACKGROUND: Patients with primary antibody deficiency (PAD) frequently suffer from pulmonary complications, associated with severe morbidity and mortality. Hence, regular pulmonary screening by computed tomography (CT) scanning is advised. However, predictive risk factors for pulmonary morbidity are lacking. OBJECTIVE: To identify patients with PAD at risk for pulmonary complications necessitating regular CT screening. METHODS: A retrospective, longitudinal cohort study of patients with PAD (median follow-up 7.4 [2.3-14.8] years) was performed. CTs were scored using the modified Brody-II scoring system. Clinical and laboratory parameters were retrospectively collected. Potential risk factors were identified by univariate analysis when P < .2 and confirmed by multivariable logistic regression when P < .05. RESULTS: The following independent risk factors for progression of airway disease (AD) were identified: (1) diagnosis of X-linked agammaglobulinemia (XLA), (2) recurrent airway infections (2.5/year), and (3) the presence of AD at baseline. Signs of AD progression were detected in 5 of 11 patients with XLA and in 17 of 80 of the other patients with PAD. Of the 22 patients who progressed, 17 had pre-existent AD scores ≥7.0%. Increased AD scores were related to poorer forced expiratory volume in 1 second values and chronic cough. Common variable immunodeficiency and increased CD4 effector/memory cells were risk factors for an interstitial lung disease (ILD) score ≥13.0%. ILD ≥13.0% occurred in 12 of 80 patients. Signs of ILD progression were detected in 8 of 80 patients, and 4 of 8 patients showing progression had pre-existent ILD scores ≥13.0%. CONCLUSION: We identified risk factors that distinguished patients with PAD at risk for AD and ILD presence and progression, which could guide future screening frequency; however, independent and preferably prospective validation is needed.

Acute perimyocarditis associated with Bartonella henselae infection.

Perimyocarditis involves inflammation of the heart muscle and surrounding tissue, causing reduced left ventricular ejection fraction. Typically viral, but occasionally bacterial, this condition can arise from Bartonella henselae, a rare yet potentially serious pathogen that can lead to cardiac inflammation and subsequent heart failure. Since this bacterium is mainly associated with cat scratch disease-which is self-limiting and has a mild disease course-B. henselae's potential role in cardiac disease is underestimated. We present a mid-30s man, immunocompetent, who presented to the emergency department with acute heart failure due to B. henselae-associated perimyocarditis. Despite not recalling any scratches or bites from cats, the patient had been living with cats, which likely exposed him. This case highlights the varied clinical presentations of B. henselae-associated heart disease and underscores the importance of considering this pathogen as a potential cause of perimyocarditis, particularly in individuals with exposure to cats.

Association between epicardial adipose tissue and cardiac dysfunction in subjects with severe obesity.

AIM: Epicardial adipose tissue (EAT) plays a role in obesity-related heart failure with preserved ejection fraction. However, the association of EAT thickness with the development of cardiac dysfunction in subjects with severe obesity without known cardiovascular disease is unclear. The aim of this study was to determine the association between EAT thickness and cardiac dysfunction and describe the potential value of EAT as an early marker of cardiac dysfunction. METHODS AND RESULTS: Subjects with body mass index ≥35 kg/m2 aged 35 to 65 years, who were referred for bariatric surgery, without suspicion of or known cardiac disease, were enrolled. Conventional transthoracic echocardiography and strain analyses were performed. A total of 186 subjects were divided into tertiles based on EAT thickness, of whom 62 were in EAT-1 (EAT <3.8 mm), 63 in EAT-2 (EAT 3.8-5.4 mm), and 61 in EAT-3 (EAT >5.4 mm). Parameters of systolic and diastolic function were comparable between tertiles. Patients in EAT-3 had the lowest global longitudinal strain (GLS) and left atrial contractile strain (LASct). Linear regression showed that a one-unit increase in EAT thickness (mm) was independently associated with a decrease in GLS (%) (ß coefficient -0.404, p = 0.002), and a decrease in LASct (%) (ß coefficient -0.544, p = 0.027). Furthermore, EAT-3 independently predicted cardiac dysfunction as defined by a GLS <18% (odds ratio 2.8, p = 0.013) and LASct <14% (odds ratio 2.5, p = 0.045). CONCLUSIONS: Increased EAT thickness in subjects with obesity without known cardiac disease was independently associated with subclinical cardiac dysfunction. Our findings suggest that EAT might play a role in the early stages of cardiac dysfunction in obesity before this may progress to overt clinical disease.

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.

Potential role of left atrial strain in estimation of left atrial pressure in patients with chronic heart failure.

AIMS: In a large proportion of heart failure with reduced ejection fraction (HFrEF) patients, echocardiographic estimation of left atrial pressure (LAP) is not possible when the ratio of the peak early left ventricular filling velocity over the late filling velocity (E/A ratio) is not available, which may occur due to several potential causes. Left atrial reservoir strain (LASr) is correlated with LV filling pressures and may serve as an alternative parameter in these patients. The aim of this study was to determine whether LASr can be used to estimate LAP in HFrEF patients in whom E/A ratio is not available. METHODS AND RESULTS: Echocardiograms of chronic HFrEF patients were analysed and LASr was assessed with speckle tracking echocardiography. LAP was estimated using the current ASE/EACVI algorithm. Patients were divided into those in whom LAP could be estimated using this algorithm (LAPe) and into those in whom this was not possible because E/A ratio was not available (LAPne). We assessed the prognostic value of LASr on the primary endpoint (PEP), which comprised the composite of hospitalization for the management of acute or worsened HF, left ventricular assist device implantation, cardiac transplantation, and cardiovascular death, whichever occurred first in time. We studied 153 patients with a mean age of 58 years of whom 76% men and 82% who were in NYHA class I-II. A total of 86 were in the LAPe group and 67 in the LAPne group. LASr was significantly lower in the LAPne group as compared with the LAPe group (15.8% vs. 23.8%, P < 0.001). PEP-free survival at a median follow-up of 2.5 years was 78% in LAPe versus 51% in LAPne patients. An increase in LASr was significantly associated with a reduced risk of the PEP in LAPne patients (adjusted hazard ratio: 0.91 per %, 95% confidence interval 0.84-0.98). An abnormal LASr (<18%) was associated with a five-fold increase in reaching the PEP. CONCLUSIONS: In HFrEF patients in whom echocardiographic estimation of LAP is not possible due to due to unavailability of E/A ratio, assessing LASr potentially carries added clinical and prognostic value.

Cardiac Surgery in Jehovah's Witnesses: 329 Consecutive Cases.

OBJECTIVES: This study aimed to describe the outcome of Jehovah's Witnesses (JWs) undergoing cardiac surgery at the authors' center. DESIGN: A single-center retrospective cohort study. SETTING: At a cardiovascular center with a tertiary intensive care unit (ICU) and specific experience with cardiac surgery in JWs. The institutional protocol describing all perioperative care in JWs has been applied for 21 years. PARTICIPANTS: All JWs undergoing cardiac surgery in the Amphia Hospital from January 1, 2001 to January 31, 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study cohort comprised 329 JWs undergoing cardiac surgery. Twenty-three patients (6.8%) were treated preoperatively for anemia. The mean European System for Cardiac Operative Risk Evaluation score was 5.1 (range 0-18). Coronary artery bypass grafting (53.2%) was performed most frequently, followed by aortic valve replacement (13.4%). Mean preoperative hemoglobin levels were 14.5 g/dL (range 9.8-18.5 g/dL), dropping to 11.6 g/dL (range 6.6-15.6 g/dL) at hospital discharge. Mean blood loss was 439 ± 349 mL in the first 12 hours postsurgery. Maximum mean postoperative troponin levels were 431 ± 424 ng/L. Resternotomy and postoperative myocardial infarction occurred in 3.6% and 4.2% of patients, respectively. On average, patients had an ICU stay of 1.4 ± 1.8 days and a hospital stay of 6.8 ± 4.2 days. Hospital mortality was 0.6% and was related to cardiac failure. CONCLUSIONS: This study demonstrated that cardiac surgery in JWs is safe when adhering to a strict perioperative patient blood management protocol.

Concomitant ligament injuries can be left untreated during surgery of distal radial fractures.

Instability of the distal radioulnar joint and scapholunate dissociation may cause pain, functional impairment and subsequent arthrosis. There is no consensus about whether these injuries should be treated acutely in patients undergoing surgery for distal radial fractures. We conducted a prospective cohort study to determine whether concomitant distal radioulnar joint instability or scapholunate dissociation negatively influence patient-related outcomes in these patients. The primary outcome was the patient-reported wrist/hand evaluation at 6 and 12 months after surgery. Out of 62 patients, 58% and 27% had intraoperative distal radioulnar joint instability and scapholunate dissociation, respectively. No significant differences were found in patient-reported scores at follow-up between patients with stable and unstable distal radioulnar joints, nor between patients with and without scapholunate dissociation. Sixty-three per cent of patients with an unstable distal radioulnar joint during surgery were stable on retesting after 6 months. Our study suggests that a wait-and-see policy in these patients therefore seems reasonable.Level of evidence: III.

Echocardiographic follow-up after cardiac rehabilitation designed for patients with obesity.

We hypothesize that a novel tailor-made cardiac rehabilitation (CR) program for obesity patients (OPTICARE XL) has better outcomes as compared to usual CR regarding parameters of cardiac function as measured by conventional and advanced transthoracic echocardiography. This is an open-label, randomized controlled trial. Inclusion criteria were: patients referred to CR with a body mass index (BMI) ≥30 kg/m2, and age ≥18 years with either coronary artery disease or nonvalvular atrial fibrillation. The experimental group participated in OPTICARE XL and the controls received the usual CR. Subjects randomized to OPTICARE XL received on top of usual CR behavioural therapy for a healthy diet and an active lifestyle for the first 12 weeks. Also, the exercise program was more tailored. Furthermore, a behavioural after-care program was organized with 6 meetings between weeks 13-52. Transthoracic (speckle tracking) echocardiography was performed at baseline and one-year follow-up. A total of 42 patients completed the follow-up, 21 in both groups. There was a mild but statistically significant reduction in weight over time, however, this was comparable between groups. There was no improvement observed in any of the echocardiographic parameters. In conclusion, cardiac function in obesity patients was not improved one-year after a novel tailor-made CR program (OPTICARE XL) as compared to usual CR.

Heart failure treatment in patients with and without obesity with an ejection fraction below 50.

BACKGROUND: The aim of this study was to assess heart failure (HF) treatment in patients with and without obesity in a large contemporary real-world Western European cohort. METHODS: Patients with a left ventricular ejection fraction (LVEF) <50% and available information on body mass index (BMI) were selected from the CHECK-HF registry. The CHECK-HF registry included chronic HF patients in the period between 2013 and 2016 in 34 Dutch outpatient clinics. Patients were divided into BMI categories. Differences in HF medical treatment were analysed, and multivariable logistic regression analysis (dichotomized as BMI <30 kg/m2 and ≥30 kg/m2 ) was performed. RESULTS: Seven thousand six hundred seventy-one patients were included, 1284 (16.7%) had a BMI ≥30 kg/m2 , and 618 (8.1%) had a BMI ≥35 kg/m2 . Median BMI was 26.4 kg/m2 . Patients with obesity were younger and had a higher rate of comorbidities such as diabetes mellitus, hypertension and obstructive sleep apnoea (OSAS). Prescription rates of guideline-directed medical therapy (GDMT) increased significantly with BMI. The differences were most pronounced for mineralocorticoid receptor antagonists (MRAs) and diuretics. Patients with obesity more often received the guideline-recommended target dose. In multivariable logistic regression, obesity was significantly associated with a higher likelihood of receiving ≥100% of the guideline-recommended target dose of beta-blockers (OR 1.34, 95% CI 1.10-1.62), renin-angiotensin system (RAS)-inhibitors (OR 1.34, 95% CI 1.15-1.57) and MRAs (OR 1.40, 95% CI 1.04-1.87). CONCLUSIONS: Guideline-recommended HF drugs are more frequently prescribed and at a higher dose in patients with obesity as compared to HF patients without obesity.

Randomized double-blind placebo-controlled crossover trial with pyridostigmine in spinal muscular atrophy types 2-4.

Hereditary proximal spinal muscular atrophy causes weakness and increased fatigability of repetitive motor functions. The neuromuscular junction is anatomically and functionally abnormal in patients with spinal muscular atrophy. Pharmacological improvement of neuromuscular transmission may therefore represent a promising additional treatment strategy. We conducted a Phase II, monocentre, placebo-controlled, double-blind, cross-over trial with the acetylcholinesterase inhibitor pyridostigmine in treatment-naïve patients with spinal muscular atrophy types 2-4. We investigated the safety and efficacy of pyridostigmine on fatigability and motor function. Each participant received pyridostigmine and a placebo for 8 weeks, in random order. Primary outcomes were the repeated nine-hole peg test for fatigability and motor function measure. Secondary outcomes were patient-reported effects, endurance shuttle test combined scores and adverse events. We included 35 patients. For the repeated nine-hole peg test, the mean difference was 0.17 s/trial (95% confidence interval: -1.17-1.49; P = 0.8), favouring placebo, and for the motor function measure, 0.74% (95% confidence interval: 0.00-1.49; P = 0.05), favouring pyridostigmine. Around 74% of patients reported medium-to-large beneficial effects of pyridostigmine on fatigability, compared with 29.7% in the placebo arm. This was paralleled by a reduced dropout risk of 70% on the endurance shuttle test combined scores (hazard ratio: 0.30; 95% confidence interval: 0.15-0.58) under pyridostigmine. Adverse events, mostly mild and self-limiting, occurred more frequently under pyridostigmine. No serious adverse events related to the study medication were observed. Patients with spinal muscular atrophy tolerated pyridostigmine well. There were no significant differences in primary outcomes, but the self-reported reduction of fatigability and improved endurance shuttle test combined score performance suggest that pyridostigmine may be useful as an additional therapy to survival motor neuron-augmenting drugs. Trial registration number: EudraCT: 2011-004369-34, NCT02941328.

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.

Decreased left atrial function in obesity patients without known cardiovascular disease.

Obesity is a risk factor for heart failure with preserved ejection fraction (HFpEF). We hypothesized that assessment of left atrial (LA) strain may be useful to reveal precursors of HFpEF in obesity patients. Echocardiograms of obesity patients without known cardiovascular disease who underwent bariatric surgery, and echocardiograms of age- and gender matched controls were analyzed. The echocardiogram was repeated 1 year after bariatric surgery. LA reservoir strain (LASr), LA conduit strain (LAScd), and LA contractile strain (LASct) were measured. 77 Obesity patients were compared with 46 non-obese controls. Obesity patients showed a significantly decreased LA function compared with non-obese individuals (LASr 32.2% ± 8.8% vs. 39.6% ± 10.8%, p < 0.001; LAScd 20.1% ± 7.5% vs. 24.9% ± 8.3%, p = 0.001; LASct 12.1% ± 3.6% vs. 14.5% ± 5.5%, p = 0.005). There was no difference in prevalence of diastolic dysfunction between the obesity group and controls (9.1% vs. 2.2%, p = 0.139). One year after bariatric surgery, LASr improved (32.1% ± 8.9% vs. 34.2% ± 8.7%, p = 0.048). In the multivariable linear regression analysis, BMI was associated with LASr, LAScd, and LASct (ß = - 0.34, CI - 0.54 to - 0.13; ß = - 0.22, CI - 0.38 to - 0.06; ß = - 0.10, CI - 0.20 to - 0.004). Obesity patients without known cardiovascular disease have impairment in all phases of LA function. LA dysfunction in obesity may be an early sign of cardiac disease and may be a predictor for developing HFpEF. LASr improved 1 year after bariatric surgery, indicating potential reversibility of LA function in obesity.

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.

[Therapeutic effect of a nasal swab: an accidental vagal manoeuvre in a patient with supraventricular tachycardia]. / Nasale swab werkte therapeutisch bij supraventriculaire tachycardie.

BACKGROUND: The case gives the reader a valuable insight in pathophysiology and treatment in atrioventricular nodal re-entry tachycardia (AVNRT) and vagal manoeuvres available to treat this phenomenon. CASE DESCRIPTION: A 85-year-old woman with a medical history of heart failure and aortic valve stenosis presents herself on the Emergency Department with cardiac shock and cardiac asthma. The ECG showed an AVNRT with 170 beats per minute (bpm) and a left bundle branch block (LBBB). After nasal swab for COVID-19 cardiac rhythm converted to a sinus or atrial tachycardia with 116bpm. The patients circulatory status improved and could then be treated with diuretics. Nasal swabs can lead to stimulation of the glossopharyngeal nerve with increase parasympathetic activity leading to a remission of atrioventricular re-entry tachycardia. CONCLUSION: Nasal swabs can lead to increased parasympathetic activity in the atrioventricular node and cause conversion of supraventricular tachycardia to sinus rhythm.

Three-dimensional QCA-based vessel fractional flow reserve (vFFR) in Heart Team decision-making: a multicentre, retrospective, cohort study.

OBJECTIVES: To evaluate the feasibility of three-vessel three-dimensional (3D) quantitative coronary angiography (QCA)-based fractional flow reserve (FFR) computation in patients discussed within the Heart Team in whom the treatment decision was based on angiography alone, and to evaluate the concordance between 3D QCA-based vessel FFR (vFFR)-confirmed functional lesion significance and revascularisation strategy as proposed by the Heart Team. DESIGN: Retrospective, cohort. SETTING: 3D QCA-based FFR indices have not yet been evaluated in the context of Heart Team decision-making; consecutive patients from six institutions were screened for eligibility and three-vessel vFFR was computed by blinded analysts. PARTICIPANTS: Consecutive patients with chronic coronary syndrome or unstable angina referred for Heart Team consultation. Exclusion criteria involved: presentation with acute myocardial infarction (MI), significant valve disease, left ventricle ejection fraction <30%, inadequate quality of angiogram precluding vFFR computation in all three epicardial coronary arteries (ie, absence of a minimum of two angiographic projections with views of at least 30° apart, substantial foreshortening/overlap of the vessel, poor contrast medium injection, ostial lesions, chronic total occlusions). PRIMARY AND SECONDARY OUTCOME MEASURES: Discordance between vFFR-confirmed lesion significance and revascularisation was assessed as the primary outcome measure. Rates of major adverse cardiac events (MACE) defined as cardiac death, MI and clinically driven revascularisation were reported. RESULTS: Of a total of 1003 patients were screened for eligibility, 416 patients (age 65.6±10.6, 71.2% male, 53% stable angina) were included. The most important reason for screening failure was insufficient quality of the angiogram (43%). Discordance between vFFR confirmed lesion significance and revascularisation was found in 124/416 patients (29.8%) corresponding to 149 vessels (46/149 vessels (30.9%) were reclassified as significant and 103/149 vessels (69.1%) as non-significant by vFFR). Over a median of 962 days, the cumulative incidence of MACE was 29.7% versus 18.5% in discordant versus concordant patients (p=0.031). CONCLUSIONS: vFFR computation is feasible in around 40% of the patients referred for Heart Team discussion, a limitation that is mostly based on insufficient quality of the angiogram. Three vessel vFFR screening indicated discordance between vFFR confirmed lesion significance and revascularisation in 29.8% of the patients.

Cardiovascular Biomarker Profiles in Obesity and Relation to Normalization of Subclinical Cardiac Dysfunction after Bariatric Surgery.

AIMS: We aimed to gain insight into the underlying pathophysiology of cardiac dysfunction in obesity patients and the improvement of cardiac function after weight loss. METHODS: This is a longitudinal study in which 92 cardiovascular biomarkers were measured by multiplex immunoassays in obesity patients without known cardiovascular disease, before and one year after bariatric surgery. RESULTS: Out of 100 eligible patients, 72 patients completed the follow-up. A total of 72 (78%) biomarkers changed significantly. The biomarkers with the highest relative changes represented processes linked mainly to insulin resistance and inflammation. In the patients with persistent subclinical cardiac dysfunction, the baseline values of 10 biomarkers were different from values in patients with normalization of cardiac function. Most of these biomarkers were linked to inflammation or atherosclerosis. Finally, a model was developed to investigate the relationship between changes in the biomarkers and persistent subclinical cardiac dysfunction. Seven biomarkers were retained in this model, mainly linked to inflammation, atherosclerosis, and hypercoagulability. CONCLUSION: The majority (78%) of cardiovascular biomarkers changed, pointing mainly to modulation of insulin resistance and inflammation. The baseline levels of 10 biomarkers, as well as pre- to post-bariatric surgery changes in seven biomarkers, were related to persistent subclinical cardiac dysfunction after bariatric surgery.