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Background: Steroidal mineralocorticoid receptor antagonists reduce morbidity and mortality among patients with heart failure and reduced ejection fraction, but their efficacy in those with heart failure and mildly reduced or preserved ejection fraction has not been established. Data regarding the efficacy and safety of the nonsteroidal mineralocorticoid receptor antagonist finerenone in patients with heart failure and mildly reduced or preserved ejection fraction are needed., Methods: In this international, double-blind trial, we randomly assigned patients with heart failure and a left ventricular ejection fraction of 40% or greater, in a 1:1 ratio, to receive finerenone (at a maximum dose of 20 mg or 40 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of total worsening heart failure events (with an event defined as a first or recurrent unplanned hospitalization or urgent visit for heart failure) and death from cardiovascular causes. The components of the primary outcome and safety were also assessed., Results: Over a median follow-up of 32 months, 1083 primary-outcome events occurred in 624 of 3003 patients in the finerenone group, and 1283 primary-outcome events occurred in 719 of 2998 patients in the placebo group (rate ratio, 0.84; 95% confidence interval [CI], 0.74 to 0.95; P = 0.007). The total number of worsening heart failure events was 842 in the finerenone group and 1024 in the placebo group (rate ratio, 0.82; 95% CI, 0.71 to 0.94; P = 0.006). The percentage of patients who died from cardiovascular causes was 8.1% and 8.7%, respectively (hazard ratio, 0.93; 95% CI, 0.78 to 1.11). Finerenone was associated with an increased risk of hyperkalemia and a reduced risk of hypokalemia., Conclusions: In patients with heart failure and mildly reduced or preserved ejection fraction, finerenone resulted in a significantly lower rate of a composite of total worsening heart failure events and death from cardiovascular causes than placebo. (Funded by Bayer; FINEARTS-HF ClinicalTrials.gov number, NCT04435626.)., (Copyright © 2024 Massachusetts Medical Society.)

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: 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., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: To describe the baseline characteristics of participants in the FINEARTS-HF trial, contextualized with prior trials including patients with heart failure (HF) with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF). The FINEARTS-HF trial is comparing the effects of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo in reducing cardiovascular death and total worsening HF events in patients with HFmrEF/HFpEF., Methods and Results: Patients with symptomatic HF, left ventricular ejection fraction (LVEF) ≥40%, estimated glomerular filtration rate ≥ 25 ml/min/1.73 m 2 , elevated natriuretic peptide levels and evidence of structural heart disease were enrolled and randomized to finerenone titrated to a maximum of 40 mg once daily or matching placebo. We validly randomized 6001 patients to finerenone or placebo (mean age 72 ± 10 years, 46% women). The majority were New York Heart Association functional class II (69%). The baseline mean LVEF was 53 ± 8% (range 34-84%); 36% of participants had a LVEF <50% and 64% had a LVEF ≥50%. The median N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 1041 (interquartile range 449-1946) pg/ml. A total of 1219 (20%) patients were enrolled during or within 7 days of a worsening HF event, and 3247 (54%) patients were enrolled within 3 months of a worsening HF event. Compared with prior large-scale HFmrEF/HFpEF trials, FINEARTS-HF participants were more likely to have recent (within 6 months) HF hospitalization and greater symptoms and functional limitations. Further, concomitant medications included a larger percentage of sodium-glucose cotransporter 2 inhibitors and angiotensin receptor-neprilysin inhibitors than previous trials., Conclusions: FINEARTS-HF has enrolled a broad range of high-risk patients with HFmrEF and HFpEF. The trial will determine the safety and efficacy of finerenone in this population., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Several ethnic minorities have an increased risk of cardiovascular events, but previous European trials that investigated clinical outcome after coronary stenting did not assess the patients' ethnic background., Aims: To compare ethnic minority and Western European trial participants in terms of both cardiovascular risk profile and 1‑year clinical outcome after percutaneous coronary intervention., Methods: In the BIO-RESORT and BIONYX randomised trials, which assessed new-generation drug-eluting stents, information on patients' self-reported ethnic background was prospectively collected. Pooled patient-level data of 5803 patients, enrolled in the Netherlands and Belgium, were analysed in this prespecified analysis. The main endpoint was target vessel failure after 1 year., Results: Patients were classified as belonging to an ethnic minority (n = 293, 5%) or of Western European origin (n = 5510, 95%). Follow-up data were available in 5772 of 5803 (99.5%) patients. Ethnic minority patients were younger, less often female, more often current smokers, more often medically treated for diabetes, and more often had a positive family history of coronary artery disease. The main endpoint target vessel failure did not differ between ethnic minority and Western European patients (3.5% vs 4.9%, hazard ratio 0.71, 95% confidence interval 0.38-1.33; p = 0.28). There was also no difference in mortality, myocardial infarction, and repeat revascularisation rates., Conclusions: Despite the unfavourable cardiovascular risk profile of ethnic minority patients, short-term clinical outcome after treatment with contemporary drug-eluting stents was highly similar to that in Western European patients. Further efforts should be made to ensure the enrolment of more ethnic minority patients in future coronary stent trials., (© 2024. The Author(s).)

Patients with peripheral arterial disease (PADs), undergoing percutaneous coronary intervention (PCI), have higher adverse event risks. The effect of invasiveness of PADs treatment on PCI outcome is unknown. This study assessed the impact of the invasiveness of previous PADs treatment (invasive or non-invasive) on event risks after PCI with contemporary drug-eluting stents. This post-hoc analysis pooled 3-year patient-level data of PCI all-comer patients living in the eastern Netherlands, previously treated for PADs. PADs included symptomatic atherosclerotic lesion in the lower or upper extremities; carotid or vertebral arteries; mesenteric arteries or aorta. Invasive PADs treatment comprised endarterectomy, bypass surgery, percutaneous transluminal angioplasty, stenting or amputation; non-invasive treatment consisted of medication and participation in exercise programs. Primary endpoint was (coronary) target vessel failure: composite of cardiac mortality, target vessel-related myocardial infarction, or clinically indicated target vessel revascularization. Of 461 PCI patients with PADs, information on PADs treatment was available in 357 (77.4%) patients; 249 (69.7%) were treated invasively and 108 (30.3%) non-invasively. Baseline and PCI procedural characteristics showed no between-group difference. Invasiveness of PADs treatment was not associated with adverse event risks, including target vessel failure (20.5% vs. 16.0%; HR: 1.30, 95%-CI 0.75-2.26, p = 0.35), major adverse cardiac events (23.3% vs. 20.4%; HR: 1.16, 95%-CI 0.71-1.90, p = 0.55), and all-cause mortality (12.1% vs. 8.3%; HR: 1.48, 95%-CI 0.70-3.13, p = 0.30). In PADs patients participating in PCI trials, we found no significant relation between the invasiveness of previous PADs treatment and 3-year outcome after PCI. Consequently, high-risk PCI patients can be identified by consulting medical records, searching for PADs, irrespective of the invasiveness of PADs treatment., (© 2024. The Author(s).)

Aims: Current heart failure (HF) guidelines recommend to prescribe four drug classes in patients with HF with reduced ejection fraction (HFrEF). A clear challenge exists to adequately implement guideline-directed medical therapy (GDMT) regarding the sequencing of drugs and timely reaching target dose. It is largely unknown how the paradigm shift from a serial and sequential approach for drug therapy to early parallel application of the four drug classes will be executed in daily clinical practice, as well as the reason clinicians may not adhere to new guidelines. We present the design and rationale for the real-world TITRATE-HF study, which aims to assess sequencing strategies for GDMT initiation, dose titration patterns (order and speed), intolerance for GDMT, barriers for implementation, and long-term outcomes in patients with de novo, chronic, and worsening HF., Methods and Results: A total of 4000 patients with HFrEF, HF with mildly reduced ejection fraction, and HF with improved ejection fraction will be enrolled in >40 Dutch centres with a follow-up of at least 3 years. Data collection will include demographics, physical examination and vital parameters, electrocardiogram, laboratory measurements, echocardiogram, medication, and quality of life. Detailed information on titration steps will be collected for the four GDMT drug classes. Information will include date, primary reason for change, and potential intolerances. The primary clinical endpoints are HF-related hospitalizations, HF-related urgent visits with a need for intravenous diuretics, all-cause mortality, and cardiovascular mortality., Conclusions: TITRATE-HF is a real-world multicentre longitudinal registry that will provide unique information on contemporary GDMT implementation, sequencing strategies (order and speed), and prognosis in de novo, worsening, and chronic HF patients., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Patients with premature coronary artery disease (CAD) have a higher incidence of myocardial infarction (MI) than patients with non-premature CAD. The aim of the present study is to asess differences in clinical outcome after a first acute MI, percutaneously treated with new-generation drug-eluting stents between patients with premature and non-premature CAD., Methods and Results: We pooled and analysed the characteristics and clinical outcome of all patients with a first MI (and no previous coronary revascularization) at time of enrolment, in four large-scale drug-eluting stent trials. Coronary artery disease was classified premature in men aged <50 and women <55 years. Myocardial infarction patients with premature and non-premature CAD were compared. The main endpoint was major adverse cardiac events (MACE): all-cause mortality, any MI, emergent coronary artery bypass surgery, or clinically indicated target lesion revascularization. Of 3323 patients with a first MI, 582 (17.5%) had premature CAD. These patients had lower risk profiles and underwent less complex interventional procedures than patients with non-premature CAD. At 30-day follow-up, the rates of MACE [hazard ratio (HR): 0.22, 95% confidence interval (CI): 0.07-0.71; P = 0.005), MI (HR: 0.22, 95% CI: 0.05-0.89; P = 0.020), and target vessel failure (HR: 0.30, 95% CI: 0.11-0.82; P = 0.012) were lower in patients with premature CAD. At 1 year, premature CAD was independently associated with lower rates of MACE (adjusted HR: 0.50, 95% CI: 0.26-0.96; P = 0.037) and all-cause mortality (adjusted HR: 0.24, 95% CI: 0.06-0.98; P = 0.046). At 2 years, premature CAD was independently associated with lower mortality (adjusted HR: 0.16, 95% CI: 0.05-0.50; P = 0.002)., Conclusions: First MI patients with premature CAD, treated with contemporary stents, showed lower rates of MACE and all-cause mortality than patients with non-premature CAD, which is most likely related to differences in cardiovascular risk profile. TWENTE trials: TWENTE I, clinicaltrials.gov: NCT01066650), DUTCH PEERS (TWENTE II, NCT01331707), BIO-RESORT (TWENTE III, NCT01674803), and BIONYX (TWENTE IV, NCT02508714)., Competing Interests: Conflict of interest: C.v.B. reports that the research department of Thoraxcentrum Twente has received research grants provided by Abbott Vascular, Biotronik, Boston Scientific, and Medtronic. R.L.A. reports a teaching grant from Biotronik, a license from Sanofi, a speaking fee from Abiomed and support from Amgen for attending a meeting, all outside the submitted work. All other authors declared that they have no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: We assessed differences in risk profile and 3-year outcome between patients undergoing percutaneous coronary intervention (PCI) for premature and non-premature coronary artery disease (CAD)., Background: The prevalence of CAD increases with age, yet some individuals develop obstructive CAD at younger age., Methods: Among participants in four randomized all-comers PCI trials, without previous coronary revascularization or myocardial infarction (MI), we compared patients with premature (men <50 years; women <55 years) and non-premature CAD. Various clinical endpoints were assessed, including multivariate analyses., Results: Of 6,171 patients, 887 (14.4%) suffered from premature CAD. These patients had fewer risk factors than patients with non-premature CAD, but were more often smokers (60.7% vs. 26.4%) and overweight (76.2% vs. 69.8%). In addition, premature CAD patients presented more often with ST-segment elevation MI and underwent less often treatment of multiple vessels, and calcified or bifurcated lesions. Furthermore, premature CAD patients had a lower all-cause mortality risk (adj.HR: 0.23, 95%-CI: 0.10-0.52; p  < 0.001), but target vessel revascularization (adj.HR: 1.63, 95%-CI: 1.18-2.26; p  = 0.003) and definite stent thrombosis risks (adj.HR: 2.24, 95%-CI: 1.06-4.72; p  = 0.034) were higher. MACE rates showed no statistically significant difference (6.6% vs. 9.4%; adj.HR: 0.86, 95%-CI: 0.65-1.16; p  = 0.33)., Conclusions: About one out of seven PCI patients was treated for premature CAD. These patients had less complex risk profiles than patients with non-premature CAD; yet, their risk of repeated revascularization and stent thrombosis was higher. As lifetime event risk of patients with premature CAD is known to be particularly high, further efforts should be made to improve modifiable risk factors such as smoking and overweight., Twente Trials: (TWENTE I, clinicaltrials.gov: NCT01066650 ), DUTCH PEERS (TWENTE II, NCT01331707 ), BIO-RESORT (TWENTE III, NCT01674803 ), and BIONYX (TWENTE IV, NCT02508714 )., Competing Interests: CvB reports that the research department of Thoraxcentrum Twente has received research grants provided by Abbott Vascular, Biotronik, Boston Scientific, and Medtronic. RLA reports a teaching grant from Biotronik, a license from Sanofi, a speaking fee from Abiomed and support from Amgen for attending a meeting, all outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Pinxterhuis, Ploumen, Zocca, Doggen, Schotborgh, Anthonio, Roguin, Danse, Benit, Aminian, Hartmann, Linssen and von Birgelen.)

Introduction: Heart failure (HF) is a heterogeneous syndrome, and the specific sub-category HF with mildly reduced ejection fraction (EF) range (HFmrEF; 41-49% EF) is only recently recognised as a distinct entity. Cluster analysis can characterise heterogeneous patient populations and could serve as a stratification tool in clinical trials and for prognostication. The aim of this study was to identify clusters in HFmrEF and compare cluster prognosis., Methods and Results: Latent class analysis to cluster HFmrEF patients based on their characteristics was performed in the Swedish HF registry (n = 7316). Identified clusters were validated in a Dutch cross-sectional HF registry-based dataset CHECK-HF (n = 1536). In Sweden, mortality and hospitalisation across the clusters were compared using a Cox proportional hazard model, with a Fine-Gray sub-distribution for competing risks and adjustment for age and sex. Six clusters were discovered with the following prevalence and hazard ratio with 95% confidence intervals (HR [95%CI]) vs. cluster 1: 1) low-comorbidity (17%, reference), 2) ischaemic-male (13%, HR 0.9 [95% CI 0.7-1.1]), 3) atrial fibrillation (20%, HR 1.5 [95% CI 1.2-1.9]), 4) device/wide QRS (9%, HR 2.7 [95% CI 2.2-3.4]), 5) metabolic (19%, HR 3.1 [95% CI 2.5-3.7]) and 6) cardio-renal phenotype (22%, HR 2.8 [95% CI 2.2-3.6]). The cluster model was robust between both datasets., Conclusion: We found robust clusters with potential clinical meaning and differences in mortality and hospitalisation. Our clustering model could be valuable as a clinical differentiation support and prognostic tool in clinical trial design., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: In patients with peripheral arterial disease (PADs), who underwent percutaneous coronary intervention (PCI), little is known about the potential impact of using different new-generation drug-eluting stents (DES) on outcome. In PCI all-comers, the results of most between-stent comparisons-stratified by strut thickness-suggested some advantage of coronary stents with ultrathin-struts. The current post-hoc analysis aimed to assess outcomes of PCI with ultrathin-strut biodegradable polymer sirolimus-eluting stents (BP-SES) vs. thin-strut durable polymer zotarolimus-eluting stents (DP-ZES) in patients with PADs., Methods: We pooled 3-year patient-level data from two large-scale randomized all-comer trials to compare Orsiro ultrathin-strut BP-SES vs. Resolute-type thin-strut DP-ZES in trial participants with concomitant PADs. BIO-RESORT (December 2012 to August 2015) and BIONYX (October 2015 to December 2016) included all-comer patients who were aged 18 years or older, capable of providing informed consent, and required a PCI. The trials had web-based randomization, with block sizes of 4 and 8, performed in a 1:1:1 or 1:1 fashion. Assessors, research staff, and patients were blinded to the type of stent used. We assessed the composite main clinical endpoint target vessel failure [TVF: cardiac death, target vessel related myocardial infarction (MI), or clinically indicated target vessel revascularization (TVR)], its components, and stent thrombosis., Results: Of 4,830 trial participants, 360 had PADs: 177 (49.2%) were treated with BP-SES and 183 (50.8%) with DP-ZES. Baseline characteristics were similar. For BP-SES, the 3-year TVF rate was 11.0% and for DP-ZES 17.9% [hazard ratio (HR): 0.59, 95% CI: 0.33-1.04; P=0.07]. For BP-SES, the TVR rate was lower than for DP-ZES (4.1% vs. 11.0%; HR: 0.36, 95% CI: 0.15-0.86; P=0.016), but this did not translate into between-group differences in cardiac death or MI. In small vessels (<2.75 mm), the TVR rate was also lower in BP-SES (5.6% vs. 13.9%; HR: 0.32, 95% CI: 0.11-0.91; P=0.024). Definite-or-probable stent thrombosis rates were 1.2% and 2.3% (P=0.43)., Conclusions: In PCI patients with PADs, the 3-year TVF incidence was numerically lower in the ultrathin-strut BP-SES vs. the thin-strut DP-ZES group. Furthermore, TVR risk was significantly lower in ultrathin-strut BP-SES, mainly driven by a lower TVR rate in small vessels., Trial Registration: BIO-RESORT trial: clinicaltrials.gov ( NCT01674803 ); BIONYX trial: clinicaltrials.gov ( NCT02508714 )., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-22-584/coif). EHP reports that the Research Department of Thoraxcentrum Twente has received institutional research grants from these companies (Biotronik, Boston Scientific, and Medtronic) for performing the 2 RCTs on which the analyses of this manuscript are based. In addition, the Research Department of Thoraxcentrum Twente has received an institutional research grant for performing a stent study, not directly related with the content of the present manuscript. RLA reports a teaching grant from Biotronik, a license from Sanovi, a speaking fee from Abiomed and support from Amgen for attending a meeting, all outside the submitted work. CvB reports that the Research Department of Thoraxcentrum Twente has received institutional research grants from these companies (Biotronik, Boston Scientific, and Medtronic) for performing the 2 RCTs on which the analyses of this manuscript are based. In addition, the Research Department of Thoraxcentrum Twente has received an institutional research grant for performing a stent study, not directly related with the content of the present manuscript. The author is a DSMB member in a TAVI trial and a vascular surgical trial. The other authors have no conflicts of interest to declare., (2023 Cardiovascular Diagnosis and Therapy. All rights reserved.)

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/m 2 and ≥30 kg/m 2 ) was performed., Results: Seven thousand six hundred seventy-one patients were included, 1284 (16.7%) had a BMI ≥30 kg/m 2 , and 618 (8.1%) had a BMI ≥35 kg/m 2 . Median BMI was 26.4 kg/m 2 . 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., (© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Objective: Positive psychology interventions (PPIs) have been found to be effective for psychiatric and somatic disorders. However, a systematic review and meta-analysis of studies examining the effectiveness of PPIs for patients with cardiovascular disease (CVD) is lacking. This systematic review and meta-analysis aims to synthesize studies examining the effectiveness of PPIs and to examine their effects on mental well-being and distress using meta-analyses., Methods: This study was preregistered on OSF (https://osf.io/95sjg/). A systematic search was performed in PsycINFO, PubMed and Scopus. Studies were included if they examined the effectiveness of PPIs on well-being for patients with CVD. Quality assessment was based on the Cochrane tool for assessing risk of bias. Three-level mixed-effects meta-regression models were used to analyze effect sizes of randomized controlled trials (RCTs)., Results: Twenty studies with 1222 participants were included, of which 15 were RCTs. Included studies showed high variability in study and intervention characteristics. Meta-analyses showed significant effects for mental well-being (β = 0.33) and distress (β = 0.34) at post-intervention and the effects were still significant at follow-up. Five of the 15 RCTs were classified as having fair quality, while the remaining had low quality., Conclusion: These results suggest that PPIs are effective in improving well-being and distress in patients with CVD and could therefore be a valuable addition for clinical practice. However, there is a need for more rigorous studies that are adequately powered and that help us understand what PPIs are most effective for which patient., Competing Interests: Declaration of Competing Interest The third author (G.C.M. Linssen) works as cardiologist for the funder (Ziekenhuisgroep Twente), but declares that this had no influence on the work presented in the paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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., Findings: 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., Interpretation: 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., Funding: The Dutch Ministry of Health, Health Care Institute (Zorginstituut), and Abbott Laboratories., Competing Interests: Declaration of interests JJB received an independent research grant from Abbott for investigator-initiated studies to the hospital and reports speaker engagement or advisory board fees from Astra Zeneca, Abbott, Boehringer Ingelheim, Bayer, Daiichi Sankyo, Novartis, and Vifor. CAdF received consulting or speaker fees from Astra Zeneca, Abbott, Boehringer Ingelheim, Novartis, Pfizer, Bristol Myers Squibb, Philips, and Servier. CJWB served on advisory boards, or had speaker engagements with Abbott, AstraZeneca, Boehringer Ingelheim, and Novartis. HPB-LR reports unrestricted research grants from Vifor, Novartis, and Roche Diagnostics, and reports consultancy fees and payments for lectures from Vifor, Novartis, Boehringer Ingelheim, AstraZeneca, and Roche Diagnostic. RAdB has received research grants or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals, Ionis Pharmaceuticals, Novo Nordisk, and Roche; and has had speaker engagements with Abbott, AstraZeneca, Bayer, Bristol Myers Squibb, Novartis, and Roche. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aims: Hyperkalaemia is observed frequently in heart failure (HF) patients and is associated with an impaired prognosis and underuse of mineralocorticoid receptor antagonists (MRAs). However, the effects of serum potassium on prescription of the full guideline recommended daily dose of 50 mg in real-world daily practice are unknown. Therefore, we investigated serum potassium and its association with the prescribed MRA dose in a large cohort of chronic HF patients., Methods and Results: A total of 5346 patients with chronic HF with a left ventricular ejection fraction ≤40% from 34 Dutch outpatient HF clinics between 2013 and 2016 were analysed on serum potassium and MRA (spironolactone and eplenerone) dose. Data were stratified by potassium as a serum potassium level <4.0, 4.0 to 5.0 or >5.0 mmol/L. Multivariable logistic regression models were used to assess the association between serum potassium and MRA dose and to adjust for potential confounders. Mean serum potassium was 4.4 ± 0.5 mmol/L and hyperkalaemia (serum potassium >5.0 mmol/L) was present in 399 patients (7.5%). MRA was used in 3091 patients (58.1%). Patients with hyperkalaemia significantly less often received ≥100% of the target dose (50 mg) compared with patients with a serum potassium between 4.0-5.0 mmol/L and <4.0 mmol/L (7.7% vs. 9.5% vs. 13.6% respectively, P = 0.0078). In the multivariable regression analyses, patients with hyperkalaemia were significantly less likely to receive ≥100% of the target dose compared with patients with serum potassium 4.0-5.0 mmol/L (OR 0.38, 95% CI 0.15-0.97, P = 0.044). Additionally, a one unit increase in serum potassium was significantly associated with a lower odds of receiving ≥100% of the target dose (OR 0.69, 95% CI 0.49-0.98, P = 0.036)., Conclusions: In this large registry of real-world chronic HF patients, both an increase in serum potassium and hyperkalaemia were associated with a lower odds of receiving the guideline-recommended MRA dose., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Implementation of guideline-recommended pharmacological treatment in heart failure (HF) patients remains challenging. In 2021, the European Heart Failure Association (HFA) published a consensus document in which patient profiles were created based on readily available patient characteristics and suggested that treatment adjusted to patient profile may result in better individualized treatment and improved guideline adherence. This study aimed to assess the distribution of these patient profiles and their treatment in a large real-world chronic HF cohort. Methods and results: The HFA combined categories of heart rate, blood pressure, presence of atrial fibrillation, chronic kidney disease, and hyperkalemia into eleven phenotypic patient profiles. A total of 4,455 patients with chronic HF and a left ventricular ejection fraction ≤40% with complete information on all characteristics were distributed over these profiles. In total, 1,640 patients (36.8%) could be classified into one of the HFA profiles. Three of these each comprised >5% of the population and consisted of patients with a heart rate >60 beats per minute with normal blood pressure (>90/60 mmHg) and no hyperkalemia. Conclusion: Nearly forty percent of a real-world chronic HF population could be distributed over the eleven patient profiles as suggested by the HFA. Phenotype-specific treatment recommendations are clinically relevant and important to further improve guideline implementation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Radhoe, Clephas, Linssen, Oortman, Smeele, Van Drimmelen, Schaafsma, Westendorp, Brunner-La Rocca and Brugts.)

Background: Both patients with obstructive coronary artery disease (CAD) and patients with peripheral arterial disease (PADs) have an increased bleeding risk. Information is scarce on bleeding in CAD patients, treated with percutaneous coronary intervention (PCI), who have comorbid PADs. We assessed whether PCI patients with PADs have a higher bleeding risk than PCI patients without PADs. Furthermore, in PCI patients with PADs we evaluated the extent by which bleeding increased the risk of further adverse events., Methods: Three-year pooled patient-level data of two randomized PCI trials (BIO-RESORT, BIONYX) with drug-eluting stents were analyzed to assess mortality and the composite endpoint major adverse cardiac events (MACE: all-cause mortality, any myocardial infarction, emergent coronary artery bypass surgery, or target lesion revascularization)., Results: Among 5989 all-comer patients, followed for 3 years, bleeding occurred in 7.7% (34/440) with comorbid PADs and 5.0% (279/5549) without PADs (HR: 1.59, 95%CI: 1.11-2.23, p = 0.010). Of all PADs patients, those with a bleeding had significantly higher rates of all-cause mortality (HR: 4.70, 95%CI: 2.37-9.33, p < 0.001) and MACE (HR: 2.39, 95%CI: 1.23-4.31, p = 0.003). Furthermore, PADs patients with a bleeding were older (74.4 ± 6.9 vs. 67.4 ± 9.5, p < 0.001). After correction for age and other potential confounders, bleeding remained independently associated with all-cause mortality (adj.HR: 2.97, 95%CI: 1.37-6.43, p = 0.006) while the relation of bleeding with MACE became borderline non-significant (adj.HR: 1.85, 95%CI: 0.97-3.55, p = 0.06)., Conclusion: PCI patients with PADs had a higher bleeding risk than PCI patients without PADs. In PADs patients, bleeding was associated with all-cause mortality, even after adjustment for potential confounders., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background In a previous trial, higher 5-year mortality was observed following treatment with biodegradable polymer Orsiro sirolimus-eluting stents (SES). We assessed 5-year safety and efficacy of all-comers as well as patients with diabetes treated with SES or Synergy everolimus-eluting stents (EES) versus durable polymer Resolute Integrity zotarolimus-eluting stents (ZES). Methods and Results The randomized BIO-RESORT (Comparison of Biodegradable Polymer and Durable Polymer Drug-Eluting Stents in an All Comers Population) trial enrolled 3514 all-comer patients at 4 Dutch cardiac centers. Patients aged ≥18 years who required percutaneous coronary intervention were eligible. Participants were stratified for diabetes and randomized to treatment with SES, EES, or ZES (1:1:1). The main end point was target vessel failure (cardiac mortality, target vessel myocardial infarction, or target vessel revascularization). Five-year follow-up was available in 3183 of 3514 (90.6%) patients. The main end point target vessel failure occurred in 142 of 1169 (12.7%) patients treated with SES, 130 of 1172 (11.6%) treated with EES, versus 157 of 1173 (14.1%) treated with ZES (hazard ratio [HR], 0.89 [95% CI, 0.71-1.12], P log-rank =0.31; and HR, 0.82 [95% CI, 0.65-1.04], P log-rank =0.10, respectively). Individual components of target vessel failure showed no significant between-stent difference. Very late definite stent thrombosis rates were low and similar (SES, 1.1%; EES, 0.6%; ZES, 0.9%). In patients with diabetes, target vessel failure did not differ significantly between stent-groups (SES, 19.8%; EES, 19.2%; versus ZES, 21.1% [ P log-rank =0.69 and P log-rank =0.63]). Conclusions Orsiro SES, Synergy EES, and Resolute Integrity ZES showed similar 5-year outcomes of safety and efficacy, including mortality. A prespecified stent comparison in patients with diabetes also revealed no significant differences in 5-year clinical outcomes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01674803.

Aims: One of the bothersome symptoms that heart failure (HF) patients can experience is thirst. There are limited data on the association between thirst and fluid intake and clinical variables. Therefore, the aim of this study was to describe severe thirst in stable HF patients and assess factors related to severe thirst, including actual fluid intake and sodium intake., Methods and Results: The study had a cross-sectional design. Stable HF patients from two HF clinics in the Netherlands were included and assessed thirst by a visual analogue scale ranging from 0 to 100. They also completed questionnaires on thirst distress, self-care behaviour, and HF symptoms. A 3 day food diary was completed to assess actual fluid intake and sodium intake. Finally, patients collected urine for 24 h. Patients were divided into severe and low thirst based on thirst score and thirst distress. T-tests, Mann-Whitney tests, and χ 2 tests were conducted to assess differences between both groups. Multivariable logistic regression analysis was performed to assess factors associated with severe thirst. A total of 100 patients were included (40% female, mean age 72 ± 12) of which 68 completed the food diary. The mean thirst score was 28 ± 25, and 25% experienced severe thirst. The majority of patients (94%) were prescribed a fluid restriction, 37% had a restriction between 1500 and 2000 mL, and 32% a restriction of 1500 mL. Severe thirst in the total group with 100 patients was associated with a higher dose of loop diuretics [odds ratio (OR) 3.25; 95% confidence interval (CI) 1.01-10.45; P = 0.048] and a higher urine output over 24 h (OR 1.002; 95% CI 1.00-1.003; P = 0.010). In the group of patients who completed the food diary (N = 68), severe thirst was associated with a higher sodium intake (OR 1.002; 95% CI 1.001-1.003; P = 0.003), a higher dose of loop diuretics (OR 22.69; 95% CI 2.78-185.04; P = 0.004), and more fatigue (OR 11.2; 95% CI 1.54-82.12; P = 0.017)., Conclusions: A quarter of all stable HF patients experienced severe thirst. A higher dose of loop diuretics was associated with more thirst; therefore, it might be important to review the dose of loop diuretics critically and try to decrease it in order to relieve severe thirst. Because all patients were prescribed a fluid restriction, a reconsideration of this restriction is also suggested., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background and Aims: A considerable number of patients who undergo percutaneous coronary intervention (PCI) also have peripheral arterial disease (PAD) - a signal of more advanced atherosclerosis. After bare metal and early-generation drug-eluting coronary stent implantation, PAD patients showed inferior outcome. As stents and medical treatment were further improved, we aimed to assess the impact of PAD on outcome of PCI with contemporary new-generation stents., Methods: We analyzed 3-year pooled patient-level data from 4 large-scale randomized new-generation stent trials to compare all-comer patients with and without (core lab-verified) history of symptomatic PAD, defined as obstructive lesions in peripheral locations including lower and upper extremities, carotid, vertebral, mesenteric and renal arteries. Main endpoint was target vessel failure: cardiac death, target vessel-related myocardial infarction, or clinically indicated target vessel revascularization., Results: Of all 9204 patients, 695 (7.6%) had a history of symptomatic PAD. They were older and had more often diabetes, renal failure, hypertension, hypercholesterolemia, and prior stroke. PAD was an independent risk factor for target vessel failure (adjusted-HR:1.42, 95%-CI:1.12-1.73, p = 0.001). Target vessel revascularization (adjusted-HR:1.37, 95%-CI:1.04-1.80, p = 0.026), death (adjusted-HR:1.52, 95%-CI:1.17-1.99, p = 0.002), and major adverse cardiovascular event risks (adjusted-HR:1.36, 95%-CI:1.13-1.64, p = 0.001) were also substantially higher., Conclusions: A history of symptomatic PAD still allows to simply identify patients with increased risk of unfavorable clinical outcome after PCI, including a higher risk of repeated coronary revascularization, despite using contemporary stents. In clinical practice, this knowledge about higher event risks of PAD patients is helpful both during Heart Team discussions and when informing patients about the procedural risk., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: To examine how the development of cardiovascular and renal disease (CVRD) translates to hospital healthcare costs in individuals with type 2 diabetes (T2D) initially free from CVRD., Methods: Data were obtained from the digital healthcare systems of 12 nations using a prespecified protocol. A fixed country-specific index date of 1 January was chosen to secure sufficient cohort disease history and maximal follow-up, varying between each nation from 2006 to 2017. At index, all individuals were free from any diagnoses of CVRD (including heart failure [HF], chronic kidney disease [CKD], coronary ischaemic disease, stroke, myocardial infarction [MI], or peripheral artery disease [PAD]). Outcomes during follow-up were hospital visits for CKD, HF, MI, stroke, and PAD. Hospital healthcare costs obtained from six countries, representing 68% of the total study population, were cumulatively summarized for CVRD events occurring during follow-up., Results: In total, 1.2 million CVRD-free individuals with T2D were identified and followed for 4.5 years (mean), that is, 4.9 million patient-years. The proportion of individuals indexed before 2010 was 18% (n = 207 137); 2010-2015, 31% (361 175); and after 2015, 52% (609 095). Overall, 184 420 (15.7%) developed CVRD, of which cardiorenal disease was most frequently the first disease to develop (59.7%), consisting of 23.0% HF and 36.7% CKD, and more common than stroke (16.9%), MI (13.7%), and PAD (9.7%). The total cumulative cost for CVRD was US$1 billion, of which 59.0% was attributed to cardiorenal disease, 3-, 5-, and 6-fold times greater than the costs for stroke, MI, and PAD, respectively., Conclusion: Across all nations, HF or CKD was the most frequent CVRD manifestation to develop in a low-risk population with T2D, accounting for the highest proportion of hospital healthcare costs. These novel findings highlight the importance of cardiorenal awareness when planning healthcare., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background Among heart failure (HF) patients, hospital readmissions are a major concern. The medication taken by a patient may provide information on comorbidities and conditions and may be used as an indicator to identify populations at an increased risk of HF readmission. Aim This study explored the use of non-cardiovascular medication at hospital discharge from the first HF admission in search of indicators of high risk of readmission for HF. Method The study included 22,476 HF patients from the Dutch PHARMO Database Network at their first HF hospitalization. The data was divided into training and validation sets. A Cox regression model with demographics, date of first HF hospital admission and non-cardiovascular medication present at discharge, adjusted for cardiovascular medication, was developed in the training set and subsequently implemented in the validation set. Results The study included 22,476 patients, mean age 76.7 years (range 18-104) and median follow-up time 2.5 years (range 0-15.7 years). During the study period 6,725 (29.9%) patients were readmitted for HF, with a median time-to-readmission of 7 months (range 0-14.3 years). Non-cardiovascular medication associated with a high risk of readmission for HF were identified as indicators of high risk, with no implied causal relationship. Patients prescribed antigout medications presented a 25% increased risk of readmission (HR 1.25, 95%CI 1.09-1.45, P = 0.002). Patients using insulin had an 18% higher risk of readmission versus patients not using insulin (HR 1.18, 95%CI 1.06-1.32, P = 0.002), but not versus patients treated with other blood-glucose-lowering drugs. No association between the risk of readmission and NSAIDs use was observed. Conclusion The results suggest that diabetes is responsible for the higher HF-readmission risk observed in patients prescribed insulin. The observed risk in users of antigout medication should be further investigated. The absence of an association with the use of NSAIDs should be interpreted with caution., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Aims: Although diabetes mellitus (DM) is a common co-morbidity in chronic heart failure (HF) patients, European data on concurrent HF and DM treatment are lacking. Therefore, we have studied the HF treatment of patients with and without DM. Additionally, with the recent breakthrough of sodium-glucose cotransporter 2 (SGLT2) inhibitors in the field of HF, we studied the potential impact of this new drug in a large cohort of HF patients., Methods and Results: A total of 7488 patients with chronic HF with a left ventricular ejection fraction <50% from 34 Dutch outpatient HF clinics between 2013 and 2016 were analysed on diabetic status and background HF therapy. Average age of the total population was 72.8 years (±11.7 years), and 64% of the patients were male. Diabetes was present in 29% of the patients (N = 2174). Diabetics had a worse renal function (mean estimated glomerular filtration rate 56 vs. 61 mL/min/1.73 m 2 , P < 0.001). Renin-angiotensin system inhibitors were less often prescribed in diabetics compared with non-diabetics (79% vs. 82%, P = 0.001), while no significant differences regarding other guideline-recommended HF drugs were found. Target doses of beta-blockers (23% vs. 16%, P < 0.001), renin-angiotensin system inhibitors (47% vs. 43%, P = 0.009), and mineralocorticoid receptor antagonists (57% vs. 51%, P = 0.005) were more often prescribed in diabetics than non-diabetics. Based on the latest trials on SGLT2 inhibitors, 31-64% of all HF patients would fulfil the eligibility or enrichment criteria (with vs. without N-terminal prohormone BNP criterion)., Conclusions: In this large real-world HF registry, a high prevalence of DM was observed and diabetics more often received guideline-recommended target doses. Based on current evidence, the majority of patients would fulfil the enrichment criteria of SGLT2 trials in HF and the impact of this new drug class will be large., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: This study aimed to assess the sex-specific distribution of heart failure (HF) with preserved, mid-range, and reduced ejection fraction across three health care settings., Methods and Results: In this descriptive observational study, we retrieved the distribution of HF types [with reduced ejection fraction (HFrEF), mid-range ejection fraction (HFmrEF), and preserved ejection fraction (HFpEF)] for men and women between 65 and 79 years of age in three health care settings from a single country: (i) patients with screening-detected HF in the high-risk community (i.e. those with shortness of breath, frailty, diabetes mellitus, and chronic obstructive pulmonary disease) from four screening studies, (ii) patients with confirmed HF from primary care derived from a single observational study, and (iii) patients with confirmed HF from outpatient cardiology clinics participating in a registry. Among 1407 patients from the high-risk community, 288 had screen-detected HF (15% HFrEF, 12% HFmrEF, 74% HFpEF), and 51% of the screen-detected HF patients were women. In both women (82%) and men (65%), HFpEF was the most prevalent HF type. In the routine general practice population (30 practices, 70 000 individuals), among the 160 confirmed HF cases, 35% had HFrEF, 23% HFmrEF, and 43% HFpEF, and in total, 43% were women. In women, HFpEF was the most prevalent HF type (52%), while in men, this was HFrEF (41%). In outpatient cardiology clinics (n = 34), of the 4742 HF patients (66% HFrEF, 15% HFmrEF, 20% HFpEF), 36% were women. In both women (56%) and men (71%), HFrEF was the most prevalent HF type., Conclusions: Both HF types and sex distribution vary considerably in HF patients of 65-79 years of age among health care settings. From the high-risk community through to general practice to the cardiology outpatient setting, there is a shift in HF type from HFpEF to HFrEF and a decrease in the proportion of HF patients that are women., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: A recent study suggested that women with heart failure and heart failure reduced ejection fraction might hypothetically need lower doses of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers ( = renin-angiotensin-system inhibitors) and β-blockers than men to achieve the best outcome. We assessed the current medical treatment of heart failure reduced ejection fraction in men and women in a large contemporary cohort and address the hypothetical impact of changing treatment levels in women., Methods: This analysis is part of a large contemporary quality of heart failure care project which includes 5320 (64%) men and 3003 (36%) women with heart failure reduced ejection fraction. Detailed information on heart failure therapy prescription and dosage were collected., Results: Women less often received renin-angiotensin-system inhibitors (79% vs 83%, p < 0.01), but more often β-blockers (82% vs 79%, p < 0.01) than men. Differences in guideline-recommended target doses between sexes were relatively small. Implementing a hypothetical sex-specific dosing schedule (at 50% of the current recommended dose in the European Society of Cardiology guidelines in women only) would lead to significantly higher levels of women receiving appropriate dosing (β-blocker 87% vs 54%, p < 0.01; renin-angiotensin-system inhibitor 96% vs 75%, p < 0.01). Most interestingly, the total number of women with >100% of the new hypothetical target dose would be 24% for β-blockers and 52% for renin-angiotensin-system inhibitors, which can be considered as relatively overdosed., Conclusion: In this large contemporary heart failure registry, there were significant but relatively small differences in drug dose between men and women with heart failure reduced ejection fraction. Implementation of the hypothetical sex-specific target dosing schedule would lead to considerably more women adequately treated. In contrast, we identified a group of women who might have been relatively overdosed with increased risk of side-effects and intolerance., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Objectives: To compare 2-year outcome following treatment with drug-eluting stents (DES) for acute myocardial infarction (MI) versus non-MI clinical syndromes. In acute MI patients, a stent-level comparison was performed, comparing Resolute Onyx versus Orsiro stents., Background: In patients presenting with acute MI, higher adverse event rates have been reported. So far, no clinical results >1 year have been published of acute MI patients treated with Resolute Onyx., Methods: This post-hoc analysis of the randomized BIONYX trial(NCT02508714) assessed the main outcome target vessel failure (TVF: cardiac death, target vessel MI, or target vessel revascularization) with Kaplan-Meier methods., Results: Of all 2,488 trial participants, acute MI patients (n = 1,275[51.2%]) were significantly younger and had less comorbidities than non-MI patients (n = 1,213[48.8%]). TVF rates were lower in acute MI patients (77/1,275[6.1%] vs. 103/1,213[8.6%], HR:0.70, 95%-CI 0.52-0.94; p log-rank  = 0.02), mainly driven by target vessel revascularization (4.1 vs. 6.1%, p log-rank  = 0.03). Multivariate analysis showed no independent association of clinical syndrome with TVF (adjusted-HR: 0.81, 95%-CI 0.60-1.10; p = .17). In MI patients treated with Resolute Onyx (n = 626) versus Orsiro (n = 649), there was no difference in TVF (6.2 vs. 6.1%; p log-rank  = 0.97) and its components. There was only 1(0.2%) definite-or-probable stent thrombosis in RO-ZES and 8(1.2%) in O-SES (p = .053)., Conclusions: Two years after treatment with thin-strut DES in this randomized trial, patients treated for acute MI had lower adverse event rates than non-MI patients. Yet, these findings were mainly attributable to between-group differences in patient and lesion characteristics. In patients who underwent PCI for acute MI, both Resolute Onyx and Orsiro showed favorable and similar 2-year outcomes., (© 2021 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Background: Clinical management of heart failure with preserved ejection fraction (HFpEF) centres on treating comorbidities and is likely to vary between countries. Thus, to provide insight into the current management of HFpEF, studies from multiple countries are required. We evaluated the clinical profiles and current management of patients with HFpEF in the Netherlands., Methods: We included 2153 patients with HFpEF (defined as a left ventricular ejection fraction ≥ 50%) from the CHECK-HF registry, which included patients from 2013 to 2016., Results: Median age was 77 (IQR 15) years, 55% were women and the most frequent comorbidities were hypertension (51%), renal insufficiency (45%) and atrial fibrillation (AF, 38%). Patients between 65 and 80 years and those over 80 years had on average more comorbidities (up to 64% and 74%, respectively, with two or more comorbidities) than patients younger than 65 years (38% with two or more comorbidities, p-value < 0.001). Although no specific drugs are available for HFpEF, treating comorbidities is advised. Beta-blockers were most frequently prescribed (78%), followed by loop diuretics (74%), renin-angiotensin system (RAS) inhibitors (67%) and mineralocorticoid receptor antagonists (MRAs, 39%). Strongest predictors for loop-diuretic use were older age, higher New York Heart Association class and AF., Conclusion: The medical HFpEF profile is determined by the underlying comorbidities, sex and age. Comorbidities are highly prevalent in HFpEF patients, especially in elderly HFpEF patients. Despite the lack of evidence, many HFpEF patients receive regular beta-blockers, RAS inhibitors and MRAs, often for the treatment of comorbidities., (© 2021. The Author(s).)

Aims: We aimed to derive and validate clinically useful clusters of patients with heart failure with preserved ejection fraction (HFpEF; left ventricular ejection fraction ≥50%)., Methods and Results: We derived a cluster model from 6909 HFpEF patients from the Swedish Heart Failure Registry (SwedeHF) and externally validated this in 2153 patients from the Chronic Heart Failure ESC-guideline based Cardiology practice Quality project (CHECK-HF) registry. In SwedeHF, the median age was 80 [interquartile range 72-86] years, 52% of patients were female and most frequent comorbidities were hypertension (82%), atrial fibrillation (68%), and ischaemic heart disease (48%). Latent class analysis identified five distinct clusters: cluster 1 (10% of patients) were young patients with a low comorbidity burden and the highest proportion of implantable devices; cluster 2 (30%) patients had atrial fibrillation, hypertension without diabetes; cluster 3 (25%) patients were the oldest with many cardiovascular comorbidities and hypertension; cluster 4 (15%) patients had obesity, diabetes and hypertension; and cluster 5 (20%) patients were older with ischaemic heart disease, hypertension and renal failure and were most frequently prescribed diuretics. The clusters were reproduced in the CHECK-HF cohort. Patients in cluster 1 had the best prognosis, while patients in clusters 3 and 5 had the worst age- and sex-adjusted prognosis., Conclusions: Five distinct clusters of HFpEF patients were identified that differed in clinical characteristics, heart failure drug therapy and prognosis. These results confirm the heterogeneity of HFpEF and form a basis for tailoring trial design to individualized drug therapy in HFpEF patients., (© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Patients with diabetes have more extensive coronary disease, resulting in higher risks of adverse clinical events following stenting. In all-comer patients, contemporary DES have shown excellent safety and efficacy, but data on diabetic patients are scarce. Separately for the BIO-RESORT and BIONYX trials, we assessed the 2-year clinical outcomes of diabetic patients, treated with various contemporary drug-eluting stents (DES)., Methods: We performed two prespecified secondary analyses of two randomized DES trials, which both stratified for diabetes. The main endpoint was target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization. Follow-up was finished before the COVID-19 pandemic., Results: In BIO-RESORT, 624/3514 (17.8%) had diabetes: 211 received Orsiro sirolimus-eluting stents (SES), 203 Synergy everolimus-eluting stents (EES), and 210 Resolute Integrity zotarolimus-eluting stents (RI-ZES). TVF did not differ between SES (10.2%) and EES (10.0%) versus RI-ZES (12.7%) (SES vs. RI-ZES HR:0.78, 95%-CI [0.44-1.40]; p = 0.40, EES vs. RI-ZES HR:0.79, 95%-CI [0.44-1.40]; p = 0.42). In BIONYX, 510/2488 (20.5%) patients had diabetes: 250 received SES and 260 Resolute Onyx zotarolimus-eluting stents (RO-ZES). There was no difference in TVF between SES (10.7%) versus RO-ZES (12.2%) (HR:0.88, 95%-CI [0.52-1.48]; p = 0.63)., Conclusions: There was no difference in 2-year clinical outcome among patients with diabetes, who were treated with SES, or EES, versus RI-ZES. In addition there was no difference in clinical outcome in diabetic patients, who were treated with SES versus RO-ZES. These findings may be considered as a signal of safety and efficacy of the studied DES in patients with diabetes., Competing Interests: Declaration of Competing Interest CvB reports that the research department of Thoraxcentrum Twente has received research grants provided by Abbott Vascular, Biotronik, Boston Scientific, and Medtronic. All other authors declared that they have no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Treatment of a coronary bifurcation lesion is often required in routine clinical practice, but data on the performance of very thin-strut biodegradable polymer drug-eluting stents are scarce., Methods: Comparison of biodegradable polymer and durable polymer drug-eluting stents in an all comers population (BIO-RESORT) is a prospective, multicenter randomized clinical trial that included 3514 all-comer patients, who were randomized to very thin-strut biodegradable polymer-coated sirolimus- or everolimus-eluting stents, versus thin-strut durable polymer-coated zotarolimus-eluting stents. The approach of bifurcation stenting was left at the operator's discretion, and provisional stenting was generally preferred. This prespecified analysis assessed 3-year clinical outcome of all patients in whom treatment involved at least one bifurcation with a side-branch diameter ≥1.5 mm., Results: Of all BIO-RESORT trial participants, 1236 patients were treated in bifurcation lesions and analyzed. Single- and two-stent techniques were used in 85.8% and 14.2%, respectively. 'True' bifurcation lesions (main vessel and side-branch obstructed) were treated in 31.1%. Three-year follow-up was available in 1200/1236 (97.1%) patients. The main endpoint target vessel failure (composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization) occurred in sirolimus-eluting stents in 42/412 (10.3%) and in zotarolimus-eluting stents in 49/409 (12.1%) patients (P-logrank = 0.40). In everolimus-eluting stents, target vessel failure occurred in 40/415 (9.8%) patients (vs. zotarolimus-eluting stents: P-logrank = 0.26). There was no between-stent difference in individual components of target vessel failure. Findings were consistent in patients with single-vessel treatment and patients treated with a single-stent technique., Conclusions: Three years after stenting all-comers with bifurcation lesions, clinical outcome was similar with the sirolimus-eluting and everolimus-eluting stents versus the zotarolimus-eluting stent.

Background: This study assessed the association between heart failure (HF) medication (angiotensin-converting-enzyme inhibitors (ACEI)/angiotensin-receptor blockers (ARB), beta-blockers (BB), mineralocorticoid-receptor antagonists (MRA) and diuretics) and HF readmissions in a real-world unselected group of patients after a first hospital admission for HF. Furthermore we analysed readmission rates for ACEI versus ARB and for carvedilol versus β1-selective BB and we investigated the effect of HF medication in relation to time since discharge., Methods and Findings: Medication at discharge was determined with dispensing data from the Dutch PHARMO Database Network including 22,476 patients with HF between 2001 and 2015. After adjustment for age, gender, number of medications and year of admission no associations were found for users versus non-users of ACEI/ARB (hazard ratio, HR = 1.01; 95%CI 0.96-1.06), BB (HR = 1.00; 95%CI 0.95-1.05) and readmissions. The risk of readmission for patients prescribed MRA (HR = 1.11; 95%CI 1.05-1.16) or diuretics (HR = 1.17; 95%CI 1.09-1.25) was higher than for non-users. The HR for ARB relative to ACEI was 1.04 (95%CI 0.97-1.12) and for carvedilol relative to β1-selective BB 1.33 (95%CI 1.20-1.46). Post-hoc analyses showed a protective effect shortly after discharge for most medications. For example one month post discharge the HR for ACEI/ARB was 0.77 (95%CI 0.69-0.86). Although we did try to adjust for confounding by indication, probably residual confounding is still present., Conclusions: Patients who were prescribed carvedilol have a higher or at least a similar risk of HF readmission compared to β1-selective BB. This study showed that all groups of HF medication -some more pronounced than others- were more effective immediately following discharge., Competing Interests: The authors have declared that no competing interests exist.

Objective: The objective was to assess the 2-year clinical performance of three drug-eluting stents in all-comer patients with severely calcified coronary lesions., Background: Severe lesion calcification increases cardiovascular event risk after coronary stenting, but there is a lack of data on the clinical outcome of all-comers with severely calcified lesions who were treated with more recently introduced drug-eluting stents., Methods: The BIO-RESORT trial (clinicaltrials.gov: NCT01674803) randomly assigned 3,514 all-comer patients to biodegradable polymer Synergy everolimus-eluting stents (EES) or Orsiro sirolimus-eluting stents (SES), versus durable polymer Resolute Integrity zotarolimus-eluting stents (ZES). In a post hoc analysis, we assessed 783 patients (22.3%) with at least one severely calcified target lesion., Results: At 2-year follow-up (available in 99% of patients), the main composite endpoint target vessel failure occurred in 19/252 (7.6%) of the EES and in 33/265 (12.6%) of the ZES-treated patients (p = .07). Target vessel failure occurred in 24/266 (9.1%) of the SES-treated patients (vs. ZES: p = .21). There was a difference in target vessel revascularization, which was required in EES in 6/252 (2.4%) patients and in ZES in 20/265 (7.7%) patients (p = .01); the target vessel revascularization rate in SES was 9/266 (3.4%, vs. ZES: p = .04). Multivariate analysis showed that implantation of EES, but not SES, was independently associated with lower target vessel revascularization rates than in ZES., Conclusions: In BIO-RESORT participants with severely calcified target lesions, treatment with EES was associated with a lower 2-year target vessel revascularization rate than treatment with ZES., (© 2020 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals, Inc.)