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Background: Chronic diseases are increasingly prevalent in Western countries. Once hospitalised, the chance for another hospitalisation increases sharply with large impact on well-being of patients and costs. The pattern of readmissions is very complex, but poorly understood for multiple chronic diseases. Methods: This cohort study of administrative discharge data between 2009–2014 from 21 tertiary hospitals (eight USA, five UK, four Australia, four continental Europe) investigated rates and reasons of readmissions to the same hospital within 30 days after unplanned admission with one of the following chronic conditions; heart failure; atrial fibrillation; myocardial infarction; hypertension; stroke; chronic obstructive pulmonary disease (COPD); bacterial pneumonia; diabetes mellitus; chronic renal disease; anaemia; arthritis and other cardiovascular disease. Proportions of readmissions with similar versus different diseases were analysed. Results: Of 4,901,584 admissions, 866,502 (17.7%) were due to the 12 chronic conditions. In-hospital, 43,573 (5.0%) patients died, leaving 822,929 for readmission analysis. Of those, 87,452 (10.6%) had an emergency 30-day readmission, rates ranged from 2.8% for arthritis to 18.4% for COPD. One third were readmitted with the same condition, ranging from 53% for anaemia to 11% for arthritis. Reasons for readmission were due to another chronic condition in 10% to 35% of the cases, leaving 30% to 70% due to reasons other than the original 12 conditions (most commonly, treatment related complications and infections). The chance of being readmitted with the same cause was lower in the USA, for female patients, with increasing age, more co-morbidities, during study period and with longer initial length of stay. Conclusion: Readmission in chronic conditions is very common and often caused by diseases other than the index hospitalisation. Interventions to reduce readmissions should therefore focus not only on the primary condition but on a holistic consideration of all the patient's comorbidities. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is common in chronic heart failure (HF) patients and influences the choice and effects of drug and device therapy. In this large real-world HF registry, we studied whether the presence of AF affects the prescription of guideline-recommended HF therapy. We analyzed 8253 patients with chronic HF with reduced ejection fraction (HFrEF) from 34 Dutch outpatient clinics included in the period between 2013 and 2016 treated according to the 2012 ESC guidelines. 2109 (25.6%) of these patients were in AF (mean age 76.8 ± 9.2 years, 65.0% were men) and 6.144 (74.4%) had no AF (mean age 70.7 ± 12.2 years, 63.6% were men). Patients with AF more often received beta-blockers (81.7% vs. 79.7%, p = 0.04), MRAs (57.1% vs. 51.7%, p < 0.01), diuretics (89.7% vs. 80.6%, p < 0.01) and digoxin (40.1% vs. 9.3%, p < 0.01) compared to patients without AF, whereas they less often receive renin-angiotensin-system (RAS)-inhibitors (76.1% vs. 83.1%, p < 0.01). The number of patients who received beta-blockers, RAS-inhibitor and MRA at ≥50% of the recommended target dose was comparable between those with and without AF (16.6% vs. 15.2%, p = 0.07). In this large cohort of chronic HFrEF patients, the prevalence of AF was high and we observed significant differences in prescription of both guideline-recommended HF between patients with and without AF. • HFrEF patients with AF received more often beta-blockers, MRA, diuretics and digoxin. • HFrEF patients with AF received less often RAS-inhibitors. • More insight in the efficacy and adherence of HF therapy in AF patients is needed. [ABSTRACT FROM AUTHOR]

Aims: The European Society of Cardiology (ESC) guidelines state that heart failure nurse specialists (heart-failure nurses) with specific competences are essential for a successful heart-failure-management programme. Thus, the Heart Failure Association (HFA) of the ESC developed the heart failure nurse curriculum (HFA curriculum). Several ESC member states developed cardiovascular education programmes to enable nurses to deliver high specialist care, but little is known of whether these curricula are in line with the HFA curriculum. Therefore, this paper describes the extent to which cardiovascular education programmes in Belgium, The Netherlands and Germany correspond to the HFA curriculum. Methods and results: A case study approach was adopted to obtain an in-depth understanding of the programme contents in relation to the HFA curriculum. For this purpose, representatives of the educational programmes and/or delegates of the national cardiovascular nursing organization shared their educational curricula. All of the studied cardiovascular education programmes aim to provide heart failure and/or cardiovascular nurses with essential competences for implementation of evidence based and guideline derived care. However, every cardiovascular education programme has a different focus/area of attention. Cardiovascular education in Belgium discusses aspects of all core-learning objectives of the HFA curriculum and emphasizes mostly knowledge aspects of these. Learning objectives in cardiovascular education in The Netherlands focus on chronic diseases in general and on learning objectives concerning patient education, support in self-care and management of device and pharmacological therapy. Cardiovascular education in Germany discusses most learning objectives; however, not all learning objectives receive equal attention. Conclusions: Although local cardiovascular education programmes adopt certain aspects of the HF curriculum, the curriculum as a whole is not adopted. [ABSTRACT FROM AUTHOR]

Abstract Background Whether the clinical presentation and in particular prevalence of symptoms and signs of heart failure (HF) is different in elderly versus younger patients and in those with reduced (HFrEF) versus preserved (HFpEF) left ventricular ejection fraction (LVEF) is a matter of ongoing debate. Aims To compare detailed clinical characteristics of these important subgroups and to develop a prediction rule for the differentiation of HFpEF and HFrEF based on clinical parameters. Methods The analysis was based on the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) comprising 622 patients ≥60 years with HF including the whole LVEF spectrum. Results In the groups ≥75 years and with HFpEF typical symptoms and clinical signs of HF were more prevalent as compared to those <75 years or with HFrEF, respectively. The burden of comorbidities was higher in the older age group. HFrEF could not be differentiated from HFpEF by symptom history and clinical examination alone. However, a combination of age, presence of pulmonary rales, systolic blood pressure, cause of heart failure, osteoporosis, current smoking, NT-proBNP, haemoglobin, QRS width and heart rhythm allowed to identify HFrEF versus HFpEF with a sensitivity of 81% and specificity of 90% (c-statistics 0.91). Conclusions More symptoms and signs of HF were present both in the older age group and in patients with HFpEF. HFpEF versus HFrEF could be differentiated by a set of simple clinical, laboratory and ECG parameters but not by symptom history and physical examination alone. Highlights • Clinical presentation of heart failure was different in patients 60–74 vs ≥75 years. • Clinical presentation of heart failure was different in HFrEF vs HFpEF. • Symptoms and signs of HF were more prevalent in particular in the older age group. • HFrEF vs HFpEF could not be identified by symptom history and physical examination. • HFrEF vs HFrEF might be differentiated by clinical, laboratory and ECG parameters. [ABSTRACT FROM AUTHOR]

Aims: Previous analyses suggest that heart failure (HF) therapy guided by (N-terminal pro-)brain natriuretic peptide (NT-proBNP) might be dependent on left ventricular ejection fraction, age and co-morbidities, but the reasons remain unclear.Methods and Results: To determine interactions between (NT-pro)BNP-guided therapy and HF with reduced [ejection fraction (EF) ≤45%; HF with reduced EF (HFrEF), n = 1731] vs. preserved EF [EF > 45%; HF with preserved EF (HFpEF), n = 301] and co-morbidities (hypertension, renal failure, chronic obstructive pulmonary disease, diabetes, cerebrovascular insult, peripheral vascular disease) on outcome, individual patient data (n = 2137) from eight NT-proBNP guidance trials were analysed using Cox-regression with multiplicative interaction terms. Endpoints were mortality and admission because of HF. Whereas in HFrEF patients (NT-pro)BNP-guided compared with symptom-guided therapy resulted in lower mortality [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.62-0.97, P = 0.03] and fewer HF admissions (HR = 0.80, 95% CI 0.67-0.97, P = 0.02), no such effect was seen in HFpEF (mortality: HR = 1.22, 95% CI 0.76-1.96, P = 0.41; HF admissions HR = 1.01, 95% CI 0.67-1.53, P = 0.97; interactions P < 0.02). Age (74 ± 11 years) interacted with treatment strategy allocation independently of EF regarding mortality (P = 0.02), but not HF admission (P = 0.54). The interaction of age and mortality was explained by the interaction of treatment strategy allocation with co-morbidities. In HFpEF, renal failure provided strongest interaction (P < 0.01; increased risk of (NT-pro)BNP-guided therapy if renal failure present), whereas in HFrEF patients, the presence of at least two of the following co-morbidities provided strongest interaction (P < 0.01; (NT-pro)BNP-guided therapy beneficial only if none or one of chronic obstructive pulmonary disease, diabetes, cardiovascular insult, or peripheral vascular disease present). (NT-pro)BNP-guided therapy was harmful in HFpEF patients without hypertension (P = 0.02).Conclusion: The benefits of therapy guided by (NT-pro)BNP were present in HFrEF only. Co-morbidities seem to influence the response to (NT-pro)BNP-guided therapy and may explain the lower efficacy of this approach in elderly patients. [ABSTRACT FROM AUTHOR]

Aims Previous analyses suggest that heart failure (HF) therapy guided by (N-terminal pro-)brain natriuretic peptide (NT-proBNP) might be dependent on left ventricular ejection fraction, age and co-morbidities, but the reasons remain unclear. Methods and results To determine interactions between (NT-pro)BNP-guided therapy and HF with reduced [ejection fraction (EF) ≤45%; HF with reduced EF (HFrEF), n = 1731] vs. preserved EF [EF > 45%; HF with preserved EF (HFpEF), n = 301] and co-morbidities (hypertension, renal failure, chronic obstructive pulmonary disease, diabetes, cerebrovascular insult, peripheral vascular disease) on outcome, individual patient data (n = 2137) from eight NT-proBNP guidance trials were analysed using Cox-regression with multiplicative interaction terms. Endpoints were mortality and admission because of HF. Whereas in HFrEF patients (NT-pro)BNP-guided compared with symptom-guided therapy resulted in lower mortality [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.62 - 0.97, P = 0.03] and fewer HF admissions (HR = 0.80, 95% CI 0.67 - 0.97, P = 0.02), no such effect was seen in HFpEF (mortality: HR = 1.22, 95% CI 0.76 - 1.96, P = 0.41; HF admissions HR = 1.01, 95% CI 0.67 - 1.53, P = 0.97; interactions P < 0.02). Age (74 ' 11 years) interacted with treatment strategy allocation independently of EF regarding mortality (P = 0.02), but not HF admission (P = 0.54). The interaction of age and mortality was explained by the interaction of treatment strategy allocation with co-morbidities. In HFpEF, renal failure provided strongest interaction (P < 0.01; increased risk of (NT-pro)BNP-guided therapy if renal failure present), whereas in HFrEF patients, the presence of at least two of the following co-morbidities provided strongest interaction (P < 0.01; (NT-pro)BNP-guided therapy beneficial only if none or one of chronic obstructive pulmonary disease, diabetes, cardiovascular insult, or peripheral vascular disease present). (NT-pro)BNP-guided therapy was harmful in HFpEF patients without hypertension (P = 0.02). Conclusion The benefits of therapy guided by (NT-pro)BNP were present in HFrEF only. Co-morbidities seem to influence the response to (NT-pro)BNP-guided therapy and may explain the lower efficacy of this approach in elderly patients. [ABSTRACT FROM AUTHOR]

Aims Renal failure is a major challenge in treating heart failure ( HF) patients. HF medication may deteriorate renal function, but the impact thereof on outcome is unknown. We investigated the effects of HF medication on worsening renal function ( WRF) and the relationship to outcome. Methods and results This post-hoc analysis of TIME-CHF ( NT-proBNP-guided vs. symptom-guided management in chronic HF) included patients with LVEF ≤45% and ≥1 follow-up visit ( n = 462). WRF III was defined as a rise in serum creatinine ≥0.5 mg/ dL (i.e. 44.2 µmol/L) at any time during the first 6 months. Four classes of medication were considered: loop diuretics, beta-blockers, renin-angiotensin system ( RAS)-blockers, and spironolactone. Functional principal component analysis of daily doses was used to comprehend medication over time. All-cause mortality after 18 months was the primary outcome. Interactions between WRF, medication, and outcome were tested. Patients with WRF III received on average higher loop diuretic doses ( P = 0.0002) and more spironolactone ( P = 0.02), whereas beta-blockers ( P = 0.69) did not differ and lower doses of RAS-blockers were given ( P = 0.09). There were significant interactions between WRF III, medicationn and outcome. Thus, WRF III was associated with poor prognosis if high loop diuretic doses were given ( P = 0.001), but not with low doses ( P = 0.29). The opposite was found for spironolactone (poor prognosis in the case of WRF III with no spironolactone, P <0.0001; but not with spironolactone, P = 0.31). Beta-blockers were protective in all patients ( P <0.001), but most in those with WRF III ( P <0.05 for interaction). RAS-blockade was associated with improved outcome ( P = 0.006), irrespective of WRF III. Conclusion Based on this analysis, it may be hypothesized that high doses of loop diuretics might have detrimental effects, particularly in combination with significant WRF, whereas spironolactone and beta-blockers might be protective in patients with WRF. [ABSTRACT FROM AUTHOR]

Letter regarding the article 'Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry' Do chronic heart failure patients receive optimal decongestive interventions in a real-life setting? Also, guideline-directed medication was better up-titrated in patients receiving LD dose adjustment, presuming that physician's discretion may be a stronger predictor of individualised therapy than patient's clinical status. [Extracted from the article]

Objectives: To assess independent predictors of stent thrombosis (ST) in an all-comer trial. Methods: This is an observational case-control study based on a retrospective analysis of the Basel Stent Kosten Effektivitäts Trial (BASKET) (n = 826). Patients with ST were compared to controls with regard to baseline parameters. Multivariate models were performed to identify independent predictors of ST. Results: At 36 months, there were 53 (6.4%) patients with ST, 17 (32%) of whom had early ST and 36 (68%) of whom had late/very late ST. Patients with ST were at a higher cardiovascular risk but received lower doses of statins than the controls (n = 212). Stents in ST patients were longer, had more overlap and were not as well expanded, with significantly more remaining stenoses than the stents in the controls. Multivariable analysis revealed interventions in saphenous vein grafts, malapposed stents, an overlap >3 mm, complex coronary anatomy and treatment with low-dose/no statins as risk factors for ST, while interventions in saphenous vein grafts, underexpanded or malapposed stents, a history of myocardial infarction and treatment with low-dose/no statins were risk factors for late ST. Conclusions: The use of statins might have a protective effect against ST. This observation is new, hypothesis-generating and should be evaluated in an adequately powered randomized trial. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Heart failure (HF) occurs when the adaptation mechanisms of the heart fail to compensate for stress factors, such as pressure overload, myocardial infarction, inflammation, diabetes, and cardiotoxic drugs, with subsequent ventricular hypertrophy, fibrosis, myocardial dysfunction, and chamber dilatation. Oxidative stress, defined as an imbalance between reactive oxygen species (ROS) generation and the capacity of antioxidant defense systems, has been authenticated as a pivotal player in the cardiopathogenesis of the various HF subtypes. The family of NADPH oxidases has been investigated as a key enzymatic source of ROS in the pathogenesis of HF. In this review, we discuss the importance of NADPH oxidase-dependent ROS generation in the various subtypes of HF and its implications. A better understanding of the pathogenic roles of NADPH oxidases in the failing heart is likely to provide novel therapeutic strategies for the prevention and treatment of HF. [Copyright &y& Elsevier]

Background: Drug-eluting stents (DESs) are associated with late stent thromboses, but the exact mechanism of action is unknown. Objective: The goal of this article was to assess the clinical interaction of glycoprotein IIb/IIIa inhibitors (GPIs) with different stent and vessel types in unselected patients undergoing percutaneous coronary intervention (PCI). Methods: This was a predefined retrospective analysis of the randomized controlled Basel Stent Kosten Effektivitats Trial (BASKET), which compared DES with bare-metal stents (BMSs) in patients undergoing PCI. Patients were compared for major adverse clinical events in relation to GPI use (abciximab and tirofiban) after 18 months. In a subgroup analysis prespecified in the study protocol, specific regard was given to angiographic groups at different risk levels for late events (high-risk vessels [ie, small vessels with a diameter <3.0 mm and saphenous vein grafts], and low-risk vessels [ie, large native vessels ≥3.0 mm]). Baseline differences between patients with or without GPI use were identified and incorporated into a multivariable Cox proportional hazards regression analysis if different at a <0.05 level. Results: A total of 826 patients (650 males, 176 females) were enrolled in BASKET; 301 (36%) received GPI therapy. Of these 301 patients, 255 (85%) received abciximab and 46 (15%) received tirofiban. After 18 months, the rate of cardiac death and nonfatal myocardial infarction was higher in patients with GPI use than in those without GPI use (35/301 [12%] vs 32/525 [6%]; P = 0.005). In patients undergoing PCI in anatomically low-risk vessels and receiving GPI therapy, there was a higher rate of cardiac death and nonfatal myocardial infarction at 18 months with a DES versus a BMS (22/151 [15%] vs 3/66 [5%]; P = 0.033). In patients undergoing PCI in anatomically low-risk vessels and without GPI therapy, there was no significant difference for cardiac death and nonfatal myocardial infarction (DES vs BMS, 11/207 [5%] vs 6/134 [4%]). In the multivariable analysis, GPI use (hazard ratio = 2.93; 95% CI, 1.53-5.63; P = 0.001) and age (hazard ratio = 1.034 per year increase; 95% CI, 1.008-1.062; P = 0.012) remained the only significant independent predictors of outcome. Interaction of stent type and GPI use was significant (P = 0.006). Conclusions: This retrospective analysis of the BASKET data found that GPIs and DESs used in patients with large native vessels may have an adverse interaction in terms of late stent thromboses. However, large prospective studies are needed to confirm these findings. [Copyright &y& Elsevier]

Aims: Diagnosing heart failure with preserved ejection fraction (HFpEF) is challenging. The newly proposed HFA-PEFF algorithm entails a stepwise approach. Step 1, typically performed in the ambulatory setting, establishes a pre-test likelihood. The second step calculates a score based on echocardiography and natriuretic peptides. The aim of this study is to validate the diagnostic value and establish the clinical impact of the second step of the HFA-PEFF score.Methods and Results: The second step of the HFA-PEFF score was evaluated in two independent, prospective cohorts, i.e. the Maastricht cohort (228 HFpEF patients and 42 controls) and the Northwestern Chicago cohort (459 HFpEF patients). In Maastricht, the HFA-PEFF score categorizes 11 (4%) of the total cohort with suspected HFpEF in the low-likelihood (0-1 points) and 161 (60%) in the high-likelihood category (5-6 points). A high HFA-PEFF score can rule in HFpEF with high specificity (93%) and positive predictive value (98%). A low score can rule out HFpEF with a sensitivity of 99% and a negative predictive value of 73%. The diagnostic accuracy of the score is 0.90 (0.84-0.96), by the area under the curve of the receiver operating characteristic curve. However, 98 (36%) are classified in the intermediate-likelihood category, where additional testing is advised. The distribution of the score shows a similar pattern in the Northwestern (Chicago) and Maastricht HFpEF patients (53% vs. 65% high, 43% vs. 34% intermediate, 4.8% vs. 1.3% low).Conclusion: This study validates and characterizes the HFA-PEFF score in two independent, well phenotyped cohorts. We demonstrate that the HFA-PEFF score is helpful in clinical practice for the diagnosis of HFpEF. [ABSTRACT FROM AUTHOR]

What is already known about this subject • Furosemide is an effective diuretic, but its absorption may be too slow to allow oral treatment in certain patients. What this study adds • In healthy volunteers, sublingual administration is associated with a higher Cmax, a higher bioavailability and a more accentuated initial natriuretic response than oral furosemide. Sublingual administration may offer advantages over oral administration of furosemide in certain clinical situations. Background In patients with decompensated heart failure, absorption of orally administered furosemide may be delayed, possibly leading to impaired pharmacodynamic effects. Sublingual administration may represent an alternative in such situations. Methods In a crossover study including 11 healthy men, 20 mg furosemide was administered intravenously, orally and sublingually on three different days. Pharmacokinetics and pharmacodynamics were assessed from repeated blood and urine samples. Results Compared with oral administration, sublingual administration was associated with 43% higher Cmax[difference 215 ng ml−1, 95% confidence interval (CI) 37, 392], a higher urinary recovery (8.9 vs. 7.3 mg, difference 1.6 mg, 95% CI 0.3, 2.9), an 28% higher AUC (difference 328 ng h−1 ml−1, 95% CI 24, 632) and a higher bioavailability of furosemide (59 vs. 47%, difference 12.0%, 95% CI −1.2, 25.2). Sodium excretion was higher after sublingual compared with oral administration (peak excretion rate 1.8 vs. 1.4 mmol min−1, P < 0.05), whereas urine volume did not differ significantly between the two application modes. In comparison, intravenous administration showed the expected more rapid and intense response. Conclusion Sublingually administered furosemide tablets differ in certain kinetic and dynamic properties from identical tablets given orally. Sublingual administration of furosemide may offer therapeutic advantages in certain groups of patients. [ABSTRACT FROM AUTHOR]

This article presents the results of an 18 month study on the cost-effectiveness of drug-eluting stents in patients at high or low risk of major cardiac events. To assess the value of these medical devices, the authors looked at cost of the procedure and the rate of follow-up events which were usually vessel revascularisations avoided by placement of the stents. The study found that overall costs were higher for patients with drug-eluting stents over those with bare metal stents due to the higher price of the drug-eluting stent. If used in all patients, the drug-eluting stents would not be good value for the money. They are cost effective in patients who need small vessel or bypass graft stenting but not in those who need larger vessel stenting.

Objectives: We sought to define the incidence of late clinical events and late stent thrombosis in patients treated with drug-eluting (DES) versus bare-metal stents (BMS) after the discontinuation of clopidogrel as well as their timing and outcome. Background: There is growing concern that delayed endothelialization after DES implantation may lead to late stent thrombosis and related myocardial infarction (MI) or death. However, event rates and outcomes after clopidogrel discontinuation versus BMS are unknown. Methods: A consecutive series of 746 nonselected patients with 1,133 stented lesions surviving 6 months without major events were followed for 1 year after the discontinuation of clopidogrel. Patients were assigned randomly 2:1 to DES versus BMS in BASKET (Basel Stent Kosten Effektivitäts Trial). The primary focus of this observation was cardiac death/MI. Results: Rates of 18-month cardiac death/MI were not different between DES and BMS patients. However, after the discontinuation of clopidogrel (between months 7 and 18), these events occurred in 4.9% after DES versus 1.3% after BMS implantation. Target vessel revascularization remained lower after DES, resulting in similar rates of all clinical events for this time period (DES 9.3%, BMS 7.9%). Documented late stent thrombosis and related death/target vessel MI were twice as frequent after DES versus BMS (2.6% vs. 1.3%). Thrombosis-related events occurred between 15 and 362 days after the discontinuation of clopidogrel, presenting as MI or death in 88%. Conclusions: After the discontinuation of clopidogrel, the benefit of DES in reducing target vessel revascularization is maintained but has to be balanced against an increase in late cardiac death or nonfatal MI, possibly related to late stent thrombosis. [Copyright &y& Elsevier]

Background: High-altitude pulmonary edema (HAPE) is caused by exaggerated hypoxic pulmonary vasoconstriction associated with decreased bioavailability of nitric oxide in the lungs and by impaired reabsorption of alveolar fluid. Objective: To investigate whether dexamethasone or tadalafil reduces the incidence of HAPE and acute mountain sickness (AMS) in adults with a history of HAPE. Design: Randomized, double-blind, placebo-controlled study performed in summer 2003. Setting: Ascent from 490 m within 24 hours and stay for 2 nights at 4559 m. Patients: 29 adults with previous HAPE. Intervention: Prophylactic tadalafil (10 mg), dexamethasone (8 mg), or placebo twice daily during ascent and stay at 4559 m. Measurements: Chest radiography was used to diagnose HAPE. A Lake Louise score greater than 4 defined AMS. Systolic pulmonary artery pressure was measured by using Doppler echocardiography, and nasal potentials were measured as a surrogate marker of alveolar sodium transport. Results: Two participants who received tadalafil developed severe AMS on arrival at 4559 m and withdrew from the study; they did not have HAPE at that time. High-altitude pulmonary edema developed in 7 of 9 participants receiving placebo and 1 of the remaining 8 participants receiving tadalafil but in none of the 10 participants receiving dexamethasone (P = 0.007 for tadalafil vs. placebo; P < 0.001 for dexamethasone vs. placebo). Eight of 9 participants receiving placebo, 7 of 10 receiving tadalafil, and 3 of 10 receiving dexamethasone had AMS (P = 1.0 for tadalafil vs. placebo; P = 0.020 for dexamethasone vs. placebo). At high altitude, systolic pulmonary artery pressure increased less in participants receiving dexamethasone (16 mm Hg [95% CI, 9 to 23 mm Hg]) and tadalafil (13 mm Hg [CI, 6 to 20 mm Hg]) than in those receiving placebo (28 mm Hg [CI, 20 to 36 mm Hg]) (P = 0.005 for tadalafil vs. placebo; P = 0.012 for dexamethasone vs. placebo). No statistically significant difference between groups was found in change in nasal potentials and expression of leukocyte sodium transport protein messenger RNA. Limitations: The study involved a small sample of adults with a history of HAPE. Conclusions: Both dexamethasone and tadalafil decrease systolic pulmonary artery pressure and may reduce the incidence of HAPE in adults with a history of HAPE. Dexamethasone prophylaxis may also reduce the incidence of AMS in these adults. [ABSTRACT FROM AUTHOR]

Summary Background No prospective trial-based data are available for incremental cost-effectiveness of drug-eluting stents (DES) compared with bare-metal stents (BMS) in unselected patients, as treated in everyday practice. Methods The Basel stent cost-effectiveness trial (BASKET) included 826 consecutive patients treated with angioplasty and stenting for 1281 de-novo lesions, irrespective of indication for angioplasty. Patients were randomised to one of two DES (Cypher, n=264; Taxus, n=281) or to a cobalt-chromium-based BMS (Vision, n=281) and followed up for 6 months for occurrence of major adverse cardiac events and costs. Analysis was by intention-to-treat. The primary endpoint was cost-effectiveness after 6 months, with effectiveness defined as reduction of major adverse cardiac events. Findings Cardiac death, myocardial infarction, or target vessel revascularisation occurred in 39 of 544 (7·2%) patients with DES and 34 of 280 (12·1%) with BMS (odds ratio 0·56, 95% CI 0·35-0·91; p=0·02), without significant differences between the two DES. Total costs at 6 months were higher with DES (mean &z.euro;10 544, SD 6849) than with BMS (&z.euro;9639, 9067; p<0·0001); higher stent costs of DES were not compensated for by lower follow-up costs. Incremental cost-effectiveness ratio of DES compared with BMS to avoid one major event was &z.euro;18 311, and costs per quality-adjusted life-year gained were more than &z.euro;50 000. Subgroup analyses showed that DES were more cost-effective for elderly patients in specific high-risk groups. Interpretation In a real-world setting, use of DES in all patients is less cost effective than in studies with selected patients. Use of these stents could be restricted to patients in high-risk groups. [ABSTRACT FROM AUTHOR]

Aims Methods Conclusion 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.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.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. [ABSTRACT FROM AUTHOR]

Background: We hypothesize that Alzheimer's disease (AD)-related pathology may accelerate cognitive decline in patients with cardiovascular diseases. Objective: To investigate the association between blood-based biomarkers of AD, astrocyte activation, and neurodegeneration and cognitive decline. Methods: From the multi-center Heart-Brain study, we included 412 patients with heart failure, carotid occlusive disease or vascular cognitive impairment (age:68.6±9.0) and 128 reference participants (65.7±7.5). Baseline amyloid-β42/40 (Aβ42/40), phosphorylated-tau181 (pTau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) were determined using SiMoA (Quanterix). Memory, attention, language, and executive functioning were evaluated (follow-up:2.1±0.3 years). We applied linear mixed models with terms for biomarker, time and biomarker*time interactions, adjusted for age, sex, education, and site, to assess associations between biomarkers and cognitive decline. Results: Among patients, Aβ42/40 was not associated with cognitive performance at baseline. However, lower Aβ42/40 was associated with steeper decline in global cognition (β±SE:0.04±0.02). Higher pTau181 was associated with worse baseline performance on global cognition (–0.14±0.04) and memory (–0.31±0.09) and with steeper decline in global cognition (–0.07±0.02), memory (–0.09±0.04), attention (–0.05±0.02), and language (–0.10±0.03). Higher GFAP was associated with worse baseline performance on global cognition (–0.22±0.05), memory (–0.43±0.10), attention (–0.14±0.06), language (–0.15±0.05), and executive functioning (–0.15±0.05) and steeper decline in global cognition (–0.05±0.01). Higher NfL was associated with worse baseline performance on global cognition (–0.16±0.04), memory (–0.28±0.09), attention (–0.20±0.06), and executive functioning (-0.10±0.04), but was not associated with performance over time. In reference participants, no associations were found. Conclusions: Our findings suggest that blood-based biomarkers of AD-related pathology predict cognitive decline in patients with cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Extracellular matrix protein turnover may play an important role in left atrial (LA) remodelling. The aim is to investigate the associations between matrix metalloproteinase (MMPs), tissue inhibitor of metalloproteinase (TIMP-1) and LA volume index (LAVI) and if these associations are independent of TIMP-1 levels. Participants from The Hoorn Study, a population-based cohort study (n = 674), underwent echocardiography. Serum MMPs (i.e., MMP-1, MMP-2, MMP-3, MMP-9, and MMP-10) and TIMP-1 levels were measured with ELISA. Multiple linear regression analyses were used. MMP-1 levels were not associated with LAVI. Higher MMP-2 levels were associated with larger LAVI (regression coefficient per SD increase in MMP (95% CI); 0.03 (0.01; 0.05). Higher MMP-3 and MMP-9 levels were associated with smaller LAVI; −0.04 (−0.07; −0.01) and −0.04 (−0.06; −0.02) respectively. Only in women were higher MMP-10 levels associated with larger LAVI; 0.04 (0.00; 0.07, p-interaction 0.04). Additionally, only in women were higher TIMP-1 levels associated with smaller LAVI; −0.05 (−0.09; −0.01, p-interaction 0.03). The associations between MMPs and LAVI were independent of TIMP-1 levels. In conclusion, serum MMPs are associated with LAVI, independent of CVD risk factors and TIMP-1 levels. In addition, these associations differ according to sex and within MMP subgroups. This shows that the role of MMPs in LA remodelling is complex. [ABSTRACT FROM AUTHOR]

Editorial. Examines the potential interaction of angiotensin-converting enzyme (ACE) inhibition and aspirin in congestive heart failure. Negative interaction between ACE inhibition and aspirin; Theoretic basis for the potential interaction.

Aims Methods and results Conclusion High left ventricular filling pressure increases left atrial volume and causes myocardial fibrosis, which may decrease with spironolactone. We studied clinical and proteomic characteristics associated with left atrial volume indexed by body surface area (LAVi), and whether LAVi influences the response to spironolactone on biomarker expression and clinical variables.In the HOMAGE trial, where people at risk of heart failure were randomized to spironolactone or control, we analysed 421 participants with available LAVi and 276 proteomic measurements (Olink) at baseline, month 1 and 9 (mean age 73 ± 6 years; women 26%; LAVi 32 ± 9 ml/m2). Circulating proteins associated with LAVi were also assessed in asymptomatic individuals from a population‐based cohort (STANISLAS; n = 1640; mean age 49 ± 14 years; women 51%; LAVi 23 ± 7 ml/m2). In both studies, greater LAVi was significantly associated with greater left ventricular masses and volumes. In HOMAGE, after adjustment and correction for multiple testing, greater LAVi was associated with higher concentrations of matrix metallopeptidase‐2 (MMP‐2), insulin‐like growth factor binding protein‐2 (IGFBP‐2) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) (false discovery rates [FDR] <0.05). These associations were externally replicated in STANISLAS (all FDR <0.05). Among these biomarkers, spironolactone decreased concentrations of MMP‐2 and NT‐proBNP, regardless of baseline LAVi (pinteraction > 0.10). Spironolactone also significantly reduced LAVi, improved left ventricular ejection fraction, lowered E/e', blood pressure and serum procollagen type I C‐terminal propeptide (PICP) concentration, a collagen synthesis marker, regardless of baseline LAVi (pinteraction > 0.10).In individuals without heart failure, LAVi was associated with MMP‐2, IGFBP‐2 and NT‐proBNP. Spironolactone reduced these biomarker concentrations as well as LAVi and PICP, irrespective of left atrial size. [ABSTRACT FROM AUTHOR]

Introduction: Heart failure is a serious burden on health care systems due to frequent hospital admissions. Early recognition of outpatients at risk for clinical deterioration could prevent hospitalization. Still, the role of signs and symptoms in monitoring heart failure patients is not clear. The heart failure coach is a web-based telemonitoring application consisting of a 9-item questionnaire assessment of heart failure signs and symptoms and developed to identify outpatients at risk for clinical deterioration. If deterioration was suspected, patients were contacted by a heart failure nurse for further evaluation. Methods: Heart failure coach questionnaires completed between 2015 and 2018 were collected from 287 patients, completing 18,176 questionnaires. Adverse events were defined as all-cause mortality, heart failure- or cardiac-related hospital admission or emergency cardiac care visits within 30 days after completion of each questionnaire. Multilevel logistic regression analyses were performed to assess the association between the heart failure coach questionnaire items and the odds of an adverse event. Results: No association between dyspnea and adverse events was observed (odds ratio 1.02, 95% confidence interval 0.79–1.30). Peripheral edema (odds ratio 2.21, 95% confidence interval 1.58–3.11), persistent chest pain (odds 2.06, 95% confidence interval 1.19–3.58), anxiety about heart failure (odds ratio 2.12, 95% confidence interval 1.44–3.13), and extensive struggle to perform daily activities (odds ratio 2.23, 95% confidence interval 1.38–3.62) were significantly associated with adverse outcome. Discussion: Regular assessment of more than the classical signs and symptoms may be helpful to identify heart failure patients at risk for clinical deterioration and should be an integrated part of heart failure telemonitoring programs. [ABSTRACT FROM AUTHOR]

Aim: Fibroblast growth factor 23 (FGF23) is an intensively studied biomarker at the crossroads of cardiovascular disease, heart failure (HF) and chronic kidney disease. Independent associations between increasing FGF23 levels and cardiovascular events were found in many, but not all studies. By analysing data from the TIME-CHF cohort, we sought to investigate the prognostic value of FGF23 in an elderly, multimorbid HF patient cohort. We determined differences between intact (iFGF23) and C-terminal FGF23 (cFGF23) regarding their prognostic value and their levels over time in different HF subgroups according to left ventricular ejection fraction (LVEF).Methods and Results: In this multicentre trial of 622 patients with symptomatic HF aged ≥60 years, we determined iFGF23 and cFGF23 at baseline, 3, 6 and 12-month follow-up. In unadjusted analyses, cFGF23 significantly predicted all HF-related outcomes at all time points. The predictive value of iFGF23 was less and not statistically significant at baseline. After multivariable adjustments, the association between both cFGF23 and iFGF23 and outcome lost statistical significance apart from cFGF23 at month 3. Overall, patients with preserved and mid-range LVEF had higher levels of iFGF23 and cFGF23 than those with reduced LVEF. Levels decreased significantly during the first 3 months in mid-range and reduced LVEF patients, but did not significantly change over time in those with preserved LVEF.Conclusions: Fibroblast growth factor 23 is of limited value regarding risk prediction in this elderly HF population. Potentially heterogeneous roles of FGF23 in different LVEF groups deserve further investigation. [ABSTRACT FROM AUTHOR]

Background: Collagen cross-linking is a fundamental process in dilated cardiomyopathy (DCM) and occurs when collagen deposition exceeds degradation, leading to impaired prognosis. This study investigated the associations of collagen-metabolism biomarkers with left ventricular function and prognosis in DCM. Methods: DCM patients who underwent endomyocardial biopsy, blood sampling, and cardiac MRI were included. The primary endpoint included death, heart failure hospitalization, or life-threatening arrhythmias, with a follow-up of 6 years (5–8). Results: In total, 209 DCM patients were included (aged 54 ± 13 years, 65% male). No associations were observed between collagen volume fraction, circulating carboxy-terminal propeptide of procollagen type-I (PICP), or collagen type I carboxy-terminal telopeptide [CITP] and matrix metalloproteinase [MMP]-1 ratio and cardiac function parameters. However, CITP:MMP-1 was significantly correlated with global longitudinal strain (GLS) in the total study sample (R = −0.40, p < 0.0001; lower CITP:MMP-1 ratio was associated with impaired GLS), with even stronger correlations in patients with LVEF > 40% (R = −0.70, p < 0.0001). Forty-seven (22%) patients reached the primary endpoint. Higher MMP-1 levels were associated with a worse outcome, even after adjustment for clinical and imaging predictors (1.026, 95% CI 1.002–1.051, p = 0.037), but CITP and CITP:MMP-1 were not. Combining MMP-1 and PICP improved the goodness-of-fit (LHR36.67, p = 0.004). Conclusion: The degree of myocardial cross-linking (CITP:MMP-1) is associated with myocardial longitudinal contraction, and MMP-1 is an independent predictor of outcome in DCM patients. [ABSTRACT FROM AUTHOR]

Aim: An echocardiographic algorithm derived by machine learning (e′VM) characterizes pre‐clinical individuals with different cardiac structure and function, biomarkers, and long‐term risk of heart failure (HF). Our aim was the external validation of the e′VM algorithm and to explore whether it may identify subgroups who benefit from spironolactone. Methods and results: The HOMAGE (Heart OMics in AGEing) trial enrolled participants at high risk of developing HF randomly assigned to spironolactone or placebo over 9 months. The e′VM algorithm was applied to 416 participants (mean age 74 ± 7 years, 25% women) with available echocardiographic variables (i.e. e′ mean, left ventricular end‐diastolic volume and mass indexed by body surface area [LVMi]). The effects of spironolactone on changes in echocardiographic and biomarker variables were assessed across e′VM phenotypes. A majority (>80%) had either a 'diastolic changes' (D), or 'diastolic changes with structural remodelling' (D/S) phenotype. The D/S phenotype had the highest LVMi, left atrial volume, E/e', natriuretic peptide and troponin levels (all p < 0.05). Spironolactone significantly reduced E/e' and B‐type natriuretic peptide (BNP) levels in the D/S phenotype (p < 0.01), but not in other phenotypes (p > 0.10; pinteraction <0.05 for both). These interactions were not observed when considering guideline‐recommended echocardiographic structural and functional abnormalities. The magnitude of effects of spironolactone on LVMi, left atrial volume and a type I collagen marker was numerically higher in the D/S phenotype than the D phenotype but the interaction test did not reach significance. Conclusions: In the HOMAGE trial, the e′VM algorithm identified echocardiographic phenotypes with distinct responses to spironolactone as assessed by changes in E/e' and BNP. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Patients with an assigned H SB 2 sb FPEF category higher than their assigned HFA-PEFF category (H SB 2 sb FPEF > HFA-PEFF) most often suffered from AF (82.0% vs. 14.0% and 61%, I P i < 0.001) and had the highest BMI (33.5 ± 6.5 vs. 27.9 ± 4.9 and 31.0 ± 6.1, I P i < 0.001). The HFA-PEFF and H2FPEF scores largely disagree in classifying patients with suspected heart failure with preserved ejection fraction The H SB 2 sb FPEF and HFA-PEFF scores have recently been proposed to solve the clinical dilemma of diagnosing heart failure with preserved ejection fraction (HFpEF).1,2 The H SB 2 sb FPEF score includes four clinical [age, body mass index (BMI), atrial fibrillation (AF) and hypertension] and two echocardiographic items (E/e' and right ventricular pressure). [Extracted from the article]

The vast majority of acute heart failure episodes are characterized by increasing symptoms and signs of congestion with volume overload. The goal of therapy in those patients is the relief of congestion through achieving a state of euvolaemia, mainly through the use of diuretic therapy. The appropriate use of diuretics however remains challenging, especially when worsening renal function, diuretic resistance and electrolyte disturbances occur. This position paper focuses on the use of diuretics in heart failure with congestion. The manuscript addresses frequently encountered challenges, such as (i) evaluation of congestion and clinical euvolaemia, (ii) assessment of diuretic response/resistance in the treatment of acute heart failure, (iii) an approach towards stepped pharmacologic diuretic strategies, based upon diuretic response, and (iv) management of common electrolyte disturbances. Recommendations are made in line with available guidelines, evidence and expert opinion. [ABSTRACT FROM AUTHOR]

This paper provides a practical clinical application of guideline recommendations relating to the inpatient monitoring of patients with acute heart failure, through the evaluation of various clinical, biomarker, imaging, invasive and non-invasive approaches. Comprehensive inpatient monitoring is crucial to the optimal management of acute heart failure patients. The European Society of Cardiology heart failure guidelines provide recommendations for the inpatient monitoring of acute heart failure, but the level of evidence underpinning most recommendations is limited. Many tools are available for the in-hospital monitoring of patients with acute heart failure, and each plays a role at various points throughout the patient's treatment course, including the emergency department, intensive care or coronary care unit, and the general ward. Clinical judgment is the preeminent factor guiding application of inpatient monitoring tools, as the various techniques have different patient population targets. When applied appropriately, these techniques enable decision making. However, there is limited evidence demonstrating that implementation of these tools improves patient outcome. Research priorities are identified to address these gaps in evidence. Future research initiatives should aim to identify the optimal in-hospital monitoring strategies that decrease morbidity and prolong survival in patients with acute heart failure. [ABSTRACT FROM AUTHOR]

The effect of haemodynamic monitoring of pulmonary artery pressure has predominantly been studied in the USA. There is a clear need for randomised trial data from patients treated with contemporary guideline-directed-medical-therapy with long-term follow-up in a different health-care system. MONITOR-HF was an open-label, randomised trial, done in 25 centres in the Netherlands. Eligible patients had chronic heart failure of New York Heart Association class III and a previous heart failure hospitalisation, irrespective of ejection fraction. Patients were randomly assigned (1:1) to haemodynamic monitoring (CardioMEMS-HF system, Abbott Laboratories, Abbott Park, IL, USA) or standard care. All patients were scheduled to be seen by their clinician at 3 months and 6 months, and every 6 months thereafter, up to 48 months. The primary endpoint was the mean difference in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score at 12 months. All analyses were by intention-to-treat. This trial was prospectively registered under the clinical trial registration number NTR7673 (NL7430) on the International Clinical Trials Registry Platform. Between April 1, 2019, and Jan 14, 2022, we randomly assigned 348 patients to either the CardioMEMS-HF group (n=176 [51%]) or the control group (n=172 [49%]). The median age was 69 years (IQR 61–75) and median ejection fraction was 30% (23–40). The difference in mean change in KCCQ overall summary score at 12 months was 7·13 (95% CI 1·51–12·75; p=0·013) between groups (+7·05 in the CardioMEMS group, p=0·0014, and –0·08 in the standard care group, p=0·97). In the responder analysis, the odds ratio (OR) of an improvement of at least 5 points in KCCQ overall summary score was OR 1·69 (95% CI 1·01–2·83; p=0·046) and the OR of a deterioration of at least 5 points was 0·45 (0·26–0·77; p=0·0035) in the CardioMEMS-HF group compared with in the standard care group. The freedom of device-related or system-related complications and sensor failure were 97·7% and 98·8%, respectively. Haemodynamic monitoring substantially improved quality of life and reduced heart failure hospitalisations in patients with moderate-to-severe heart failure treated according to contemporary guidelines. These findings contribute to the aggregate evidence for this technology and might have implications for guideline recommendations and implementation of remote pulmonary artery pressure monitoring. The Dutch Ministry of Health, Health Care Institute (Zorginstituut), and Abbott Laboratories. [ABSTRACT FROM AUTHOR]

Aims: In order to understand how sex differences impact the generalizability of randomized clinical trials (RCTs) in patients with heart failure (HF) and reduced ejection fraction (HFrEF), we sought to compare clinical characteristics and clinical outcomes between RCTs and HF observational registries stratified by sex. Methods and results: Data from two HF registries and five HFrEF RCTs were used to create three subpopulations: one RCT population (n = 16 917; 21.7% females), registry patients eligible for RCT inclusion (n = 26 104; 31.8% females), and registry patients ineligible for RCT inclusion (n = 20 810; 30.2% females). Clinical endpoints included all‐cause mortality, cardiovascular mortality, and first HF hospitalization at 1 year. Males and females were equally eligible for trial enrolment (56.9% of females and 55.1% of males in the registries). One‐year mortality rates were 5.6%, 14.0%, and 28.6% for females and 6.9%, 10.7%, and 24.6% for males in the RCT, RCT‐eligible, and RCT‐ineligible groups, respectively. After adjusting for 11 HF prognostic variables, RCT females showed higher survival compared to RCT‐eligible females (standardized mortality ratio [SMR] 0.72; 95% confidence interval [CI] 0.62–0.83), while RCT males showed higher adjusted mortality rates compared to RCT‐eligible males (SMR 1.16; 95% CI 1.09–1.24). Similar results were also found for cardiovascular mortality (SMR 0.89; 95% CI 0.76–1.03 for females, SMR 1.43; 95% CI 1.33–1.53 for males). Conclusion: Generalizability of HFrEF RCTs differed substantially between the sexes, with females having lower trial participation and female trial participants having lower mortality rates compared to similar females in the registries, while males had higher than expected cardiovascular mortality rates in RCTs compared to similar males in registries. [ABSTRACT FROM AUTHOR]

Blood pressure variability (BPV) is related to cerebral white matter hyperintensities (WMH), but longitudinal studies assessing WMH progression are scarce. Patients with cardiovascular disease and control participants of the Heart-Brain Connection Study underwent 24-hour ambulatory blood pressure monitoring and repeated brain MRI at baseline and after 2 years. Using linear regression, we determined whether different measures of BPV (standard deviation, coefficient of variation, average real variability (ARV), variability independent of the mean) and nocturnal dipping were associated with WMH and whether this association was mediated or moderated by baseline cerebral perfusion. Among 177 participants (mean age: 65.9 ± 8.1 years, 33.9% female), the absence of diastolic nocturnal dipping was associated with higher WMH volume at baseline (β = 0.208, 95%CI: 0.025–0.392), but not with WMH progression among 91 participants with follow-up imaging. None of the BPV measures were associated with baseline WMH. Only 24-hour diastolic ARV was significantly associated with WMH progression (β = 0.144, 95%CI: 0.030–0.258), most profound in participants with low cerebral perfusion at baseline (p-interaction = 0.042). In conclusion, absent diastolic nocturnal dipping and 24-hour diastolic ARV were associated with higher WMH volume. Whilst requiring replication, these findings suggest that blood pressure patterns and variability may be a target for prevention of small vessel disease. [ABSTRACT FROM AUTHOR]

Orthostatic hypotension (OH) is associated with an increased risk of dementia, potentially attributable to cerebral hypoperfusion. We investigated which patterns and characteristics of OH are related to cognition or to potentially underlying structural brain injury in hemodynamically impaired patients and healthy reference participants. Participants with carotid occlusive disease or heart failure, and reference participants from the Heart-Brain Connection Study underwent OH measurements, neuropsychological assessment and brain MRI. We analyzed the association between OH, global cognitive functioning, white matter hyperintensity (WMH) volume and brain parenchymal fraction with linear regression. We stratified by participant group, severity and duration of OH, chronotropic incompetence and presence of orthostatic symptoms. Of 337 participants (mean age 67.3 ± 8.8 years, 118 (35.0%) women), 113 (33.5%) had OH. Overall, presence of OH was not associated with cognitive functioning (β: −0.12 [−0.24–0.00]), but we did observe worse cognitive functioning in those with severe OH (≥ 30/15 mmHg; β: −0.18 [−0.34 to −0.02]) and clinically manifest OH (β: −0.30 [−0.52 to −0.08]). These associations did not differ significantly by OH duration or chronotropic incompetence, and were similar between patient groups and reference participants. Similarly, both severe OH and clinically manifest OH were associated with a lower brain parenchymal fraction, and severe OH also with a somewhat higher WMH volume. Severe OH and clinically manifest OH are associated with worse cognitive functioning. This supports the notion that specific patterns and characteristics of OH determine its impact on brain health. • Effects of OH on brain health may differ by OH characteristics. • OH characteristics are severity, duration, chronotropic incompetence and symptoms. • Severe OH and clinically manifest OH are related to poorer cognitive functioning. • This coincided with a significantly lower brain parenchymal fraction. • Individuals with severe OH also tended to have larger WMH volumes. [ABSTRACT FROM AUTHOR]

Awareness of transthyretin amyloid cardiomyopathy (ATTR-CM) has increased over the years due to diagnostic and therapeutic developments. Timely initiation of novel disease-modifying treatments improves both morbidity and mortality, which underlines the necessity for a prompt diagnosis. Nevertheless, early diagnosis of ATTR-CM remains challenging. This is a retrospective observational cohort study of patients diagnosed with ATTR-CM. Between 2016 and 2023, 87 patients were diagnosed with cardiac amyloidosis of which 65 (75%) patients with ATTR-CM and 22 (25%) patients with light chain amyloidosis. This study included 65 ATTR-CM patients (mean age 77 ± 7 years; 86% male) of whom 59 (91%) with wild-type ATTR-CM (ATTRwt) and six (9%) with variant ATTR-CM. We observed a surge in ATTR-CM diagnoses from 3 patients/year (2016–2020) to 16 patients/year (2021–2023), driven by ATTRwt. Nevertheless, the interval between the onset of heart failure symptoms and ATTR-CM diagnosis has not changed significantly (2016–2020 27.3 months [18.6–62.4]; 2021–2023 30.0 months [8.6–57.2]; p = 0.546), driven by time to referral. Red flags for ATTR-CM preceded diagnosis by several years: left ventricular hypertrophy (79%, 5.8 years [3.3–7.0]) and carpal tunnel syndrome (49%, 6.8 years [2.3–12.1]). Despite the presence of typical red flags, symptom-to-diagnosis duration has remained similar driven by time to referral. Improved recognition of red flags for ATTR-CM could reduce the time to diagnosis and improve overall recognition. [ABSTRACT FROM AUTHOR]

Mortality in type 2 diabetes, is determined not only by classical complications, but also by comorbidities, and is linked to hyperglycaemia and apparent even in prediabetes. We aimed to comprehensively investigate, in a population-based cohort, health burden defined as the presence of comorbidities in addition to classical complications and cardiometabolic risk factors, in not only type 2 diabetes but also prediabetes. Such population-based study has not been performed previously. Extensive phenotyping was performed in 3,410 participants of the population-based Maastricht Study (15.0% prediabetes and 28.6% type 2 diabetes) to assess presence of 17 comorbidities, six classical complications, and ten cardiometabolic risk factors. These were added up into individual and combined sum scores and categorized. Group differences were studied with multinomial regression analyses adjusted for age and sex. Individuals with type 2 diabetes and prediabetes, as compared to normal glucose metabolism (NGM), had greater comorbidities, classical complications, cardiometabolic risk factors and combined sum scores (comorbidities sum score ≥ 3: frequencies (95% CI) 61.5% (57.6;65.4) and 41.2% (36.5;45.9) vs. 25.4% (23.5;27.4), p-trend < 0.001; classical complications ≥ 2 (26.6% (23.1;30.1; P < 0.001 vs. NGM) and 10.1% (7.8;12.7; P = 0.065 vs NGM) vs. 8.0% (6.9;9.3)); cardiometabolic risk factors ≥ 6 (39.7% (35.9;43.4) and 28.5% (24.5;32.6) vs. 14.0% (12.5;15.6); p-trend < 0.001); combined ≥ 8 (66.6% (62.7;70.5) and 48.4% (43.7;53.1) vs. 26.0%(24.1;28.0), p-trend < 0.001). Type 2 diabetes and prediabetes health burden was comparable to respectively 32 and 14 years of ageing. Our population-based study shows, independently of age and sex, a considerable health burden in both type 2 diabetes and prediabetes, which to a substantial extent can be attributed to comorbidities in addition to classical complications and cardiometabolic risk factors. Our findings emphasize the necessity of comorbidities’ awareness in (pre)diabetes and for determining the exact role of hyperglycaemia in the occurrence of comorbidities. [ABSTRACT FROM AUTHOR]

While both cardiac dysfunction and progressive loss of cognitive functioning are prominent features of an aging population, surprisingly few studies have addressed the link between heart and brain function. This is probably due to the monodisciplinary approach to these problems by cardiologists, neurologists, and geriatricians. Recent data indicate that autoregulation of cerebral flow cannot always protect the brain from hypoperfusion when cardiac output is reduced or atherosclerosis is prominent. This suggests a close link between cardiac function and large vessel atherosclerosis on the one hand and brain perfusion and cognitive functioning on the other. In a national research program, we will test the hypothesis that impaired hemodynamic status of both heart and brain is an important and potentially reversible cause of vascular cognitive impairment (VCI) offering promising opportunities for treatment. Using a multidisciplinary approach, we will address the following questions: 1) To what extent do hemodynamic changes contribute to VCI? 2) What are the mechanisms involved? 3) Does improvement of the hemodynamic status lead to improvement of cognitive dysfunction? To this end we will perform clinical studies in elderly patients with clinically manifest VCI, carotid occlusive disease, or heart failure and evaluate their cardiac and large vascular function, atherosclerotic load, and cerebral perfusion with a comprehensive magnetic resonance imaging protocol and thoroughly test their cognitive function. We will also analyze epidemiological data from the Rotterdam Study. [ABSTRACT FROM AUTHOR]

Introduction: To alleviate the burden of Heart Failure (HF), the European Society of cardiology developed guidelines (ESC-guidelines) to optimise HF-diagnosis and treatment. These guidelines state that optimal HF-care is organised in a multidisciplinary programme in which pharmacological and non-pharmacological treatment is offered. Research has proven that multidisciplinary programmes and effective self-care behaviour significantly reduce HF-mortality and (re)hospitalisation, yet little is known about implementation of these ESC-guidelines. Therefore, the INTERACT study investigated current HF-care processes and guideline adherence in three North-West European regions: Maastricht (the Netherlands), Aachen (Germany) and Noorder-Kempen (Belgium). Methods: A case-study approach was adopted to study local implementation of ESC-guidelines considering non-pharmacological- and multidisciplinary care. National guidelines and local protocols were collected and studied to investigate the level of agreement with and implementation of ESC-guidelines. A matrix was developed to analyse the content of national and local guidelines and protocols in terms of non-pharmacological and multidisciplinary care. Results: All national organisations promote ESC guidelines, and some developed additional national guidelines. In region A, B and C patients receive multidisciplinary care in hospital based HF-outpatient clinics. Moreover, region B and C patients benefit from either structural (region B) or project based (region C) integrated care, in which specialist- and primary care work together to provide seamless care for HF-patients. However, in region A this seamless integrated care remains to be implemented. Conclusion: Although ESC-guidelines recommend clearly considering Multidisciplinary- and non-pharmacological care implementation may differ between regions. [ABSTRACT FROM AUTHOR]

Introduction: To alleviate the burden of Heart Failure (HF), the European Society of cardiology developed guidelines (ESC-guidelines) to optimise HF-diagnosis and treatment. These guidelines state that optimal HF-care is organised in a multidisciplinary programme in which pharmacological and non-pharmacological treatment is offered. Research has proven that multidisciplinary programmes and effective self-care behaviour significantly reduce HF-mortality and (re)hospitalisation, yet little is known about implementation of these ESC-guidelines. Therefore, the INTERACT study investigated current HF-care processes and guideline adherence in three North-West European regions: Maastricht (the Netherlands), Aachen (Germany) and Noorder-Kempen (Belgium). Methods: A case-study approach was adopted to study local implementation of ESC-guidelines considering non-pharmacological- and multidisciplinary care. National guidelines and local protocols were collected and studied to investigate the level of agreement with and implementation of ESC-guidelines. A matrix was developed to analyse the content of national and local guidelines and protocols in terms of non-pharmacological and multidisciplinary care. Results: All national organisations promote ESC guidelines, and some developed additional national guidelines. In region A, B and C patients receive multidisciplinary care in hospital based HF-outpatient clinics. Moreover, region B and C patients benefit from either structural (region B) or project based (region C) integrated care, in which specialist- and primary care work together to provide seamless care for HF-patients. However, in region A this seamless integrated care remains to be implemented. Conclusion: Although ESC-guidelines recommend clearly considering Multidisciplinary- and non-pharmacological care implementation may differ between regions. [ABSTRACT FROM AUTHOR]

Circulating biomarkers and imaging techniques provide independent and complementary information to guide management of heart failure (HF). This consensus document by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) presents current evidence‐based indications relevant to integration of imaging techniques and biomarkers in HF. The document first focuses on application of circulating biomarkers together with imaging findings, in the broad domains of screening, diagnosis, risk stratification, guidance of treatment and monitoring, and then discusses specific challenging settings. In each section we crystallize clinically relevant recommendations and identify directions for future research. The target readership of this document includes cardiologists, internal medicine specialists and other clinicians dealing with HF patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Duty-cycled (DC) radiofrequency ablation (RFA) for atrial fibrillation (AF) has been introduced, however, data on large patient series and comparison to conventional RFA are scarce. Methods: Between 2006 and 2008DC RFA was performed in 209 consecutive patients (143 (68%) paroxysmal and 66 (32%) persistent AF). As controls served 211 patients, 155 (73%) with paroxysmal and 56 (27%) with persistent AF (p =0.3). In DC RFA, the pulmonary veins (PV) were isolated followed by ablation at the septum and left atrium, if AF persisted. Conventional PV isolation was followed by anatomical lines at the roof and mitral isthmus. Results: Freedom of paroxysmal AF was demonstrated after 1.08DC RFA procedures per patient in 82% and after 1.19 conventional procedures in 87% after 8.5±6.5months (ns). In persistent AF, success rates were 79% after 1.35DC RFA procedures and 80% after 1.34 conventional procedures after 11.5±8.5months (ns). The subgroup analysis of 119 patients with follow-up ≥12months (17.5 [14.1–23.6] months) showed similar results. Left atrial flutter occurred in 3% and 8% after paroxysmal AF ablation (p <0.05) and in 12% and 23% after persistent AF ablation (p =0.1). Multivariate predictors for success in both groups were age, left atrial size, presence of persistent vs. paroxysmal AF and previous pacemaker implantation, but not the ablation technique used. Non-fatal complications were seen in 2.8% with no differences between the groups. Conclusion: Outcome in DC RFA is similar to conventional RFA with a final success rate exceeding 80% in both paroxysmal and persistent AF in the absence of fatal complications. [Copyright &y& Elsevier]