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Background and Aims: In patients with chronic heart failure (HF), the MONITOR-HF trial demonstrated the efficacy of pulmonary artery (PA)-guided HF therapy over standard of care in improving quality of life and reducing HF hospitalizations and mean PA pressure. This study aimed to evaluate the consistency of these benefits in relation to clinically relevant subgroups., Methods: The effect of PA-guided HF therapy was evaluated in the MONITOR-HF trial among predefined subgroups based on age, sex, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction, HF aetiology, cardiac resynchronization therapy, and implantable cardioverter defibrillator. Outcome measures were based upon significance in the main trial and included quality of life-, clinical-, and PA pressure endpoints, and were assessed for each subgroup. Differential effects in relation to the subgroups were assessed with interaction terms. Both unadjusted and multiple testing adjusted interaction terms were presented., Results: The effects of PA monitoring on quality of life, clinical events, and PA pressure were consistent in the predefined subgroups, without any clinically relevant heterogeneity within or across all endpoint categories (all adjusted interaction P-values were non-significant). In the unadjusted analysis of the primary endpoint quality-of-life change, weak trends towards a less pronounced effect in older patients (Pinteraction = .03; adjusted Pinteraction = .33) and diabetics (Pinteraction = .01; adjusted Pinteraction = .06) were observed. However, these interaction effects did not persist after adjusting for multiple testing., Conclusions: This subgroup analysis confirmed the consistent benefits of PA-guided HF therapy observed in the MONITOR-HF trial across clinically relevant subgroups, highlighting its efficacy in improving quality of life, clinical, and PA pressure endpoints in chronic HF patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Heart failure (HF), a global pandemic affecting millions of individuals, calls for adequate predictive guidance for improved therapy. Congestion, a key factor in HF-related hospitalizations, further underscores the need for timely interventions. Proactive monitoring of intracardiac pressures, guided by pulmonary artery (PA) pressure, offers opportunities for efficient early-stage intervention, since haemodynamic congestion precedes clinical symptoms., Methods: The BioMEMS study, a substudy of the MONITOR-HF trial, proposes a multifaceted approach integrating blood biobank data with traditional and novel HF parameters. Two additional blood samples from 340 active participants in the MONITOR-HF trial were collected at baseline, 3-, 6-, and 12-month visits and stored for the BioMEMS biobank. The main aims are to identify the relationship between temporal biomarker patterns and PA pressures derived from the CardioMEMS-HF system, and to identify the biomarker profile(s) associated with the risk of HF events and cardiovascular death., Conclusion: Since the prognostic value of single baseline measurements of biomarkers like N-terminal pro-B-type natriuretic peptide is limited, with the BioMEMS study we advocate a dynamic, serial approach to better capture HF progression. We will substantiate this by relating repeated biomarker measurements to PA pressures. This design rationale presents a comprehensive review on cardiac biomarkers in HF, and aims to contribute valuable insights into personalized HF therapy and patient risk assessment, advancing our ability to address the evolving nature of HF effectively., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Heart failure (HF) is a progressive disease in which periods of clinical stability are interrupted by episodes of clinical deterioration known as worsening heart failure (WHF). Patients who develop WHF are at high risk of subsequent death, rehospitalization, and excessive healthcare costs. As such, WHF could be seen as a separate disease stage and precursor of advanced HF. Whether WHF has a substantial health, societal, and economic impact evidence regarding its multifactorial nature and the specific barriers in treatment, including advanced HF therapies, remains scarce. The CHAIN-HF registry aims to describe the incidence, characteristics, current treatment, and outcomes of WHF. Additionally, it will promote structured regional collaboration and educate on increasing awareness for WHF and describe the implementation of guideline directed medical therapy and utilization of advanced HF therapies in a collaborative network., Methods and Results: The CHAIN-HF registry is a prospective, observational, and multicentre study from the collaborating hospitals (Rijnmond HF Network) in the Rotterdam area. Unselected and consecutive patients (irrespective of ejection fraction) with a WHF event will be included. Comprehensive data including demographics, co-morbidities, treatment, and in-hospital and post-discharge outcomes will be collected. Notably, data on socio-economic status, treatment decisions, and referral for advanced HF therapies will be included., Conclusions: CHAIN-HF will be the first prospective, dedicated WHF registry in a collaborative network of hospitals that will provide robust real-world evidence on the incidence, characteristics, and outcomes of WHF. Moreover, it will provide information on of the value of regional collaboration to improve awareness and outcomes of WHF., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: This study was performed to develop and externally validate prediction models for appropriate implantable cardioverter-defibrillator (ICD) shock and mortality to identify subgroups with insufficient benefit from ICD implantation., Methods and Results: We recruited patients scheduled for primary prevention ICD implantation and reduced left ventricular function. Bootstrapping-based Cox proportional hazards and Fine and Gray competing risk models with likely candidate predictors were developed for all-cause mortality and appropriate ICD shock, respectively. Between 2014 and 2018, we included 1441 consecutive patients in the development and 1450 patients in the validation cohort. During a median follow-up of 2.4 (IQR 2.1-2.8) years, 109 (7.6%) patients received appropriate ICD shock and 193 (13.4%) died in the development cohort. During a median follow-up of 2.7 (IQR 2.0-3.4) years, 105 (7.2%) received appropriate ICD shock and 223 (15.4%) died in the validation cohort. Selected predictors of appropriate ICD shock were gender, NSVT, ACE/ARB use, atrial fibrillation history, Aldosterone-antagonist use, Digoxin use, eGFR, (N)OAC use, and peripheral vascular disease. Selected predictors of all-cause mortality were age, diuretic use, sodium, NT-pro-BNP, and ACE/ARB use. C-statistic was 0.61 and 0.60 at respectively internal and external validation for appropriate ICD shock and 0.74 at both internal and external validation for mortality., Conclusion: Although this cohort study was specifically designed to develop prediction models, risk stratification still remains challenging and no large group with insufficient benefit of ICD implantation was found. However, the prediction models have some clinical utility as we present several scenarios where ICD implantation might be postponed., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Prescribed dosages of heart failure (HF) therapy in patients with a reduced left ventricular ejection fraction remain lower than guideline recommended. It remains unclear whether systolic blood pressure (BP) influences prescription of HF drugs to HF patients with a reduced left ventricular ejection fraction in a European setting. This study aimed to investigate the role of systolic BP on the prescription rate and actual dose of guideline-recommended HF therapy., Methods: A total of 8246 patients with chronic HF with a reduced left ventricular ejection fraction from 34 Dutch outpatient HF clinics were included. Detailed information on prescription rates and dosages of HF drugs were assessed according to systolic BP categories (<95, 95-109, 110-129, and ≥130 mm Hg)., Results: Patients with systolic BP <95 mm Hg receive more often triple therapy (β-blocker, renin-angiotensin system inhibitor, and mineralocorticoid receptor antagonist; 40.3% versus 30.4% respectively, P <0.001) compared with ≥130 mm Hg. Patients with systolic BP <95 mm Hg received significantly more often mineralocorticoid receptor antagonists (64.5% versus 43.8%), ivabradine (8.3% versus 3.6%), and diuretics (94.2% versus 78.6%) and less often renin-angiotensin system inhibitors (75.4% versus 82.8%) compared with ≥130 mm Hg ( P for all trends, <0.001). The prescribed dosages of β-blockers and renin-angiotensin system inhibitors were significantly lower in patients with systolic BP <95 mm Hg compared with ≥130 mm Hg ( P for all trends, <0.001)., Conclusions: In this large cross-sectional cohort of patients with reduced left ventricular ejection fraction, patients with lower systolic BP receive more HF drugs but at lower dose relative to the target dose recommended in HF guidelines. Discussion is warranted regarding what target BP is acceptable and what should be limiting factors in uptitration to adequate levels of HF medication.

This study aimed to investigate whether pulmonary shunt grade on transthoracic contrast echocardiography (TTCE) predicts the size of pulmonary arteriovenous malformations (PAVMs) on chest computed tomography (CT) and subsequent feasibility for transcatheter embolotherapy. We prospectively included 772 persons with possible or definite hereditary haemorrhagic telangiectasia, who underwent both TTCE and chest CT for screening of PAVMs. A quantitative three-point grading scale was used to classify the pulmonary shunt size on TTCE (grade 1-3). Transcatheter embolotherapy was performed for PAVMs deemed large enough for endovascular closure on chest CT. TTCE documented pulmonary shunting in 510 (66.1%) patients. The positive predictive value of a pulmonary shunt grade 1, 2 and 3 on TTCE for presence of PAVMs on chest CT was 13.4%, 45.3% and 92.5%, respectively (p<0.001). None of the 201 persons with a pulmonary shunt grade 1 on TTCE had PAVMs on chest CT large enough for transcatheter embolotherapy, while 38 (25.3%) and 123 (77.4%) individuals with a pulmonary shunt grade 2 and 3 on TTCE, respectively, underwent endovascular closure of PAVMs. Pulmonary shunt grade on TTCE predicts the size of PAVMs on chest CT and their feasibility for subsequent transcatheter embolotherapy. Chest CT can be safely withheld from all persons with a pulmonary shunt grade 1 on TTCE, as any PAVM found in these subjects will be too small for transcatheter embolotherapy., (© ERS 2014.)

The clinical diagnosis of hereditary hemorrhagic telangiectasia (HHT) is based on the Curaçao criteria. Three out of four criteria are required for a definite clinical diagnosis HHT, two criteria are considered "possible" HHT, and 0 or 1 criterion makes the diagnosis unlikely. However, these consensus diagnostic criteria have not been validated. We report on the diagnostic accuracy of the clinical criteria. A total of 450 consecutive persons ≥16 years of age were screened for HHT between May 2004 and September 2009, including a chest CT to screen for pulmonary arteriovenous malformations (AVMs). We selected 263 first-degree relatives of disease-causing mutation carriers who underwent mutation analysis. Genetic test results were considered the gold standard. The family mutation was present in 186 patients (mean age 42.9 ± 14.6 yr; 54.8% female). A clinical diagnosis was definite, "possible", and unlikely in 168 (90.3%), 17 (9.1%), and 1 (0.5%) patient, respectively. In 77 persons the family mutation was absent (mean age 37.1 ± 12.3 yr, 59.7% female). In this group a clinical diagnosis was definite, possible, and unlikely in 0, 35 (45.5%), and 42 (54.5%) persons, respectively. The positive predictive value of a definite clinical diagnosis was 100% (95% CI 97.8-100), the negative predictive value of an unlikely diagnosis 97.7% (95% CI 87.9-99.6). Of 52 patients with "possible" HHT, 17 (32.7%) displayed an HHT-causing mutation. The Curaçao clinical criteria have a good diagnostic performance. Genetic testing is particularly helpful in patients with a "possible" clinical diagnosis HHT., (Copyright © 2013 Wiley Periodicals, Inc.)

An increased prevalence of intrapulmonary right-to-left shunt (RLS) has been shown in patients with migraine. The aim of this study was to determine whether the size of intrapulmonary RLS was associated with migraine with aura (MA+) and migraine without aura (MA-) in subjects screened for hereditary hemorrhagic telangiectasia. A total of 462 consecutive subjects were screened for hereditary hemorrhagic telangiectasia and underwent transthoracic contrast echocardiography. A pulmonary shunt was established when contrast appeared in the left atrium after 4 cardiac cycles. Shunt size was assessed semiquantitatively as small (<30 microbubbles), moderate (30 to 100 microbubbles), or large (>100 microbubbles). A headache questionnaire was completed by 420 subjects (91%). Two independent neurologists diagnosed migraine according to the International Headache Society criteria. Of 420 screened subjects (mean age 43.4 ± 15.4 years, 61.4% women), 44 (10.5%) had MA+ and 45 (10.7%) had MA-. MA+ was an independent predictor for an intrapulmonary RLS (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.36 to 6.47, p=0.006) in multivariate analysis. MA- was not correlated with RLS (OR 1.21, 95% CI 0.56 to 2.64, p=0.60). When comparing patients with MA+ to those without migraine in a multivariate analysis, the presence of an intrapulmonary shunt predicted MA+ (OR 2.5, 95% CI 1.2 to 5.2, p=0.01), as did female gender (OR 3.15, 95% CI 1.29 to 7.65, p<0.01). The correlation of MA+ and RLS could be entirely attributed to large intrapulmonary shunts (OR 7.61, 95% CI 3.11 to 18.61, p<0.001), as small (OR 0.6, 95% CI 0.13 to 2.78, p=0.52) and moderate (OR 1.33, 95% CI 0.35 to 5.02, p=0.68) shunts did not appear to be risk factors for MA+. In conclusion, patients with large intrapulmonary RLS have an increased risk for MA+., (Copyright © 2011 Elsevier Inc. All rights reserved.)