Publications by authors named "Hans-Peter Brunner-La Rocca"

221 Publications

What to consider when implementing a tool for timely recognition of palliative care needs in heart failure: a context-based qualitative study.

BMC Palliat Care 2022 Jan 4;21(1). Epub 2022 Jan 4.

Department of Health Services Research, Care and Public Health Research Institute (CAPHRI), Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands.

Background: Needs assessment tools can facilitate healthcare professionals in timely recognition of palliative care needs. Despite the increased attention for implementation of such tools, most studies provide little or no attention to the context of implementation. The aim of this study was to explore factors that contribute positively and negatively to timely screening of palliative care needs in advanced chronic heart failure.

Methods: Qualitative study using individual interviews and focus groups with healthcare professionals. The data were analysed using a deductive approach. The Consolidated Framework for Implementation Research was used to conceptualise the contextual factors.

Results: Twenty nine healthcare professionals with different backgrounds and working in heart failure care in the Southern and Eastern parts of the Netherlands participated. Several factors were perceived to play a role, such as perception and knowledge about palliative care, awareness of palliative care needs in advanced chronic heart failure, perceived difficulty when and how to start palliative care, limited acceptance to treatment boundaries in cardiology, limited communication and collaboration between healthcare professionals, and need for education and increased attention for palliative care in advanced chronic heart failure guidelines.

Conclusions: This study clarified critical factors targeting patients, healthcare professionals, organisations to implement a needs assessment tool for timely recognition of palliative care needs in the context of advanced chronic heart failure. A multifaceted implementation strategy is needed which has attention for education, patient empowerment, interdisciplinary collaboration, identification of local champions, chronic heart failure specific guidelines and culture.
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http://dx.doi.org/10.1186/s12904-021-00896-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8723899PMC
January 2022

The effect of spironolactone in patients with obesity at risk for heart failure: proteomic insights from the HOMAGE trial.

J Card Fail 2021 Dec 18. Epub 2021 Dec 18.

Department of Cardiology, Maastricht University Medical Center, the Netherlands. Electronic address:

Background: Adipose tissue influences the expression and degradation of circulating biomarkers. We aimed to identify the biomarker profile and biological meaning of biomarkers associated with obesity, to assess the effect of spironolactone on the circulating biomarkers, and to explore whether obesity might modify the effect of spironolactone.

Methods And Results: Protein biomarkers(n=276) from the Olink®Proseek-Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline, 1 month and 9 months from the HOMAGE randomized controlled trial participants. Of the 510 participants, 299 had obesity defined as an increased waist circumference (≥102cm men and ≥88cm women). Biomarkers at baseline reflected adipogenesis, increased vascularization, reduced fibrinolysis and glucose intolerance in patients with obesity at baseline. Treatment with spironolactone had only minor effects on this proteomic profile. Obesity modified the effect of spironolactone on systolic blood pressure (p=0.001): showing a stronger decrease of blood pressure in obese patients (-14.8mmHg 95%CI: -18.45-11.12) compared to non-obese patients (-3.6mmHg 95%CI -7.82-0.66).

Conclusions: Among patients at risk for HF, those with obesity have a characteristic proteomic profile reflecting adipogenesis and glucose intolerance. Spironolactone had only minor effects on this obesity-related proteomic profile, but obesity significantly modified the effect of spironolactone on systolic blood pressure.
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http://dx.doi.org/10.1016/j.cardfail.2021.12.005DOI Listing
December 2021

Heart failure with preserved, mid-range, and reduced ejection fraction across health care settings: an observational study.

ESC Heart Fail 2021 Dec 9. Epub 2021 Dec 9.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands.

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.
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http://dx.doi.org/10.1002/ehf2.13742DOI Listing
December 2021

Diabetes and treatment of chronic heart failure in a large real-world heart failure population.

ESC Heart Fail 2021 Dec 4. Epub 2021 Dec 4.

Department of Cardiology, Thorax Center, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 40, Rotterdam, 3015GD, The Netherlands.

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 , 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.
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http://dx.doi.org/10.1002/ehf2.13743DOI Listing
December 2021

Acute heart failure and iron deficiency: a prospective, multicentre, observational study.

ESC Heart Fail 2021 Dec 4. Epub 2021 Dec 4.

Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands.

Aims: The prevalence and the natural course of iron deficiency (ID) in acute heart failure (AHF) are still unclear. We investigated the prevalence of ID in unselected patients admitted with AHF on admission, at discharge and up to 3 months thereafter.

Methods And Results: In this prospective, multicentre, observational study, 742 patients admitted with AHF were enrolled. The main study outcome was the percentage of patients with ID (ferritin <100 μg/L = absolute ID or ferritin 100-299 μg/L and transferrin saturation <20% = functional ID) at admission (T0), after clinical stabilization prior to discharge (T1), and 10 ± 6 weeks after discharge (T2). At T0, ID was present in 71.8% of the patients (44.1% absolute and 27.7% functional ID). At T1 and T2, ID was present in 56.4% (32.4% absolute and 24% functional ID) and 50.3% (36.8% absolute and 13.5% functional ID), respectively. Absolute ID persisted from T0 to T2 in 66% of the patients, while functional ID resolved in 56% of the patients. Ferritin (median [interquartile range] 124 μg/L [56-247] to 150 μg/L [73-277]), transferrin saturation (15% [10-20] to 18% [12-27]), and iron levels (9 μmol/L [6-13] to 11 μmol/L [8-16]) increased significantly (all P < 0.001) from T0 to T1. Transferrin saturation (to 21% [15-29]) and iron levels (to 13 μmol/L [9-17]) also increased significantly (both P < 0.01) from T1 to T2 without iron supplementation.

Conclusions: Iron deficiency is highly prevalent in patients with AHF, but resolves during treatment in some patients, even without iron supplementation. Absolute ID is more likely to persist over time, whereas functional ID often resolves during treatment of AHF, representing probably a reduced iron availability rather than a true deficiency.
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http://dx.doi.org/10.1002/ehf2.13737DOI Listing
December 2021

Cardiac biomarkers retain prognostic significance in patients with heart failure and chronic obstructive pulmonary disease.

J Cardiovasc Med (Hagerstown) 2022 Jan;23(1):28-36

Scuola Superiore Sant'Anna.

Aims: Chronic obstructive pulmonary disease (COPD) is a frequent comorbidity in patients with heart failure (HF). We assessed the influence of COPD on circulating levels and prognostic value of three HF biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), and soluble suppression of tumorigenesis-2 (sST2).

Methods: Individual data from patients with chronic HF, known COPD status, NT-proBNP and hs-TnT values (n = 8088) were analysed. A subgroup (n = 3414) had also sST2 values.

Results: Patients had a median age of 66 years (interquartile interval 57-74), 77% were men and 82% had HF with reduced ejection fraction. NT-proBNP, hs-TnT and sST2 were 1207 ng/l (487-2725), 17 ng/l (9-31) and 30 ng/ml (22-44), respectively. Patients with COPD (n = 1249, 15%) had higher NT-proBNP (P = 0.042) and hs-TnT (P < 0.001), but not sST2 (P = 0.165). Over a median 2.0-year follow-up (1.5-2.5), 1717 patients (21%) died, and 1298 (16%) died from cardiovascular causes; 2255 patients (28%) were hospitalized for HF over 1.8 years (0.9-2.1). NT-proBNP, hs-TnT and sST2 predicted the three end points regardless of COPD status. The best cut-offs from receiver-operating characteristics analysis were higher in patients with COPD than in those without. Patients with all three biomarkers higher than or equal to end-point- and COPD-status-specific cut-offs were also those with the worst prognosis.

Conclusions: Among patients with HF, those with COPD have higher NT-proBNP and hs-TnT, but not sST2. All these biomarkers yield prognostic significance regardless of the COPD status.
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http://dx.doi.org/10.2459/JCM.0000000000001281DOI Listing
January 2022

Clustering based on comorbidities in patients with chronic heart failure: an illustration of clinical diversity.

ESC Heart Fail 2021 Nov 18. Epub 2021 Nov 18.

Department of Research & Development, CIRO, Horn, The Netherlands.

Aims: It is increasingly recognized that the presence of comorbidities substantially contributes to the disease burden in patients with heart failure (HF). Several reports have suggested that clustering of comorbidities can lead to improved characterization of the disease phenotypes, which may influence management of the individual patient. Therefore, we aimed to cluster patients with HF based on medical comorbidities and their treatment and, subsequently, compare the clinical characteristics between these clusters.

Methods And Results: A total of 603 patients with HF entering an outpatient HF rehabilitation programme were included [median age 65 years (interquartile range 56-71), 57% ischaemic origin of cardiomyopathy, and left ventricular ejection fraction 35% (26-45)]. Exercise performance, daily life activities, disease-specific health status, coping styles, and personality traits were assessed. In addition, the presence of 12 clinically relevant comorbidities was recorded, based on targeted diagnostics combined with applicable pharmacotherapies. Self-organizing maps (SOMs; www.viscovery.net) were used to visualize clusters, generated by using a hybrid algorithm that applies the classical hierarchical cluster method of Ward on top of the SOM topology. Five clusters were identified: (1) a least comorbidities cluster; (2) a cachectic/implosive cluster; (3) a metabolic diabetes cluster; (4) a metabolic renal cluster; and (5) a psychologic cluster. Exercise performance, daily life activities, disease-specific health status, coping styles, personality traits, and number of comorbidities were significantly different between these clusters.

Conclusions: Distinct combinations of comorbidities could be identified in patients with HF. Therapy may be tailored based on these clusters as next step towards precision medicine. The effect of such an approach needs to be prospectively tested.
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http://dx.doi.org/10.1002/ehf2.13704DOI Listing
November 2021

No influence of spironolactone on plasma concentrations of angiotensin-converting enzyme 2: Findings from the HOMAGE randomized trial.

Arch Cardiovasc Dis 2021 12 9;114(12):814-817. Epub 2021 Nov 9.

Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), centre d'investigations cliniques-plurithématique 1433, Nancy, France.

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http://dx.doi.org/10.1016/j.acvd.2021.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576594PMC
December 2021

The prognostic impact of mechanical atrial dysfunction and atrial fibrillation in heart failure with preserved ejection fraction.

Eur Heart J Cardiovasc Imaging 2021 Dec;23(1):74-84

Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre+ (MUMC+), PO Box 616, 6200 MD Maastricht, the Netherlands.

Aims: This study assessed the prognostic implications of mechanical atrial dysfunction in heart failure with preserved ejection fraction (HFpEF) patients with different stages of atrial fibrillation (AF) in detail.

Methods And Results: HFpEF patients (n = 258) systemically underwent an extensive clinical characterization, including 24-h Holter monitoring and speckle-tracking echocardiography. Patients were categorized according to rhythm and stages of AF: 112 with no history of AF (no AF), 56 with paroxysmal AF (PAF), and 90 with sustained (persistent/permanent) AF (SAF). A progressive decrease in mechanical atrial function was seen: left atrial reservoir strain (LASr) 30.5 ± 10.5% (no AF), 22.3 ± 10.5% (PAF), and 13.9 ± 7.8% (SAF), P < 0.001. Independent predictors for lower LASr values were AF, absence of chronic obstructive pulmonary disease, higher N-terminal-pro hormone B-type natriuretic peptide, left atrial volume index, and relative wall thickness, lower left ventricular global longitudinal strain, and echocardiographic signs of elevated left ventricular filling pressure. LASr was an independent predictor of adverse outcome (hazard ratio per 1% decrease =1.049, 95% confidence interval 1.014-1.085, P = 0.006), whereas AF was not when the multivariable model included LASr. Moreover, LASr mediated the adverse outcome associated with AF in HFpEF (P = 0.008).

Conclusion: Mechanical atrial dysfunction has a possible greater prognostic role in HFpEF compared to AF status alone. Mechanical atrial dysfunction is a predictor of adverse outcome independently of AF presence or stage, and may be an underlying mechanism (mediator) for the worse outcome associated with AF in HFpEF. This may suggest mechanical atrial dysfunction plays a crucial role in disease progression in HFpEF patients with AF, and possibly also in HFpEF patients without AF.
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http://dx.doi.org/10.1093/ehjci/jeab222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685598PMC
December 2021

Generalisability of Randomised Controlled Trials in Heart Failure with Reduced Ejection Fraction.

Eur Heart J Qual Care Clin Outcomes 2021 Oct 1. Epub 2021 Oct 1.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

Background: Heart failure (HF) trials have stringent in- and ex- clusion criteria, but limited data exists regarding generalisability of trials. We compared patient characteristics and outcomes between patients with HF and reduced ejection fraction (HFrEF) in trials and observational registries.

Methods And Results: Individual patient data for 16922 patients from five randomised clinical trials and 46914 patients from two HF registries were included. The registry patients were categorised into trial-eligible and non-eligible groups using the most commonly used in- and ex-clusion criteria. A total of 26104 (56%) registry patients fulfilled the eligibility criteria. Unadjusted all-cause mortality rates at one year were lowest in the trial population (7%), followed by trial-eligible patients (12%) and trial-non-eligible registry patients (26%). After adjustment for age and sex, all-cause mortality rates were similar between trial participants and trial-eligible registry patients (standardised mortality ratio (SMR) 0.97; 95% confidence interval (CI) 0.92 -1.03) but cardiovascular mortality was higher in trial participants (SMR 1.19; 1.12 -1.27). After full case-mix adjustment, the SMR for cardiovascular mortality remained higher in the trials at 1.28 (1.20- 1.37) compared to RCT-eligible registry patients.

Conclusion: In contemporary HF registries, over half of HFrEF patients would have been eligible for trial enrolment. Crude clinical event rates were lower in the trials, but, after adjustment for case-mix, trial participants had similar rates of survival as registries. Despite this, they had about 30% higher cardiovascular mortality rates. Age and sex were the main drivers of differences in clinical outcomes between HF trials and observational HF registries.
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http://dx.doi.org/10.1093/ehjqcco/qcab070DOI Listing
October 2021

Prognostic value of signs and symptoms in heart failure patients using remote telemonitoring.

J Telemed Telecare 2021 Sep 13:1357633X211039404. Epub 2021 Sep 13.

Department of Cardiology, 199236Maastricht University Medical Centre, the Netherlands.

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.
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http://dx.doi.org/10.1177/1357633X211039404DOI Listing
September 2021

Integration of imaging and circulating biomarkers in heart failure: a consensus document by the Biomarkers and Imaging Study Groups of the Heart Failure Association of the European Society of Cardiology.

Eur J Heart Fail 2021 Oct 14;23(10):1577-1596. Epub 2021 Sep 14.

Christchurch Heart Institute, University of Otago, Dunedin, New Zealand.

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.
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http://dx.doi.org/10.1002/ejhf.2339DOI Listing
October 2021

The genomics of heart failure: design and rationale of the HERMES consortium.

ESC Heart Fail 2021 Dec 3;8(6):5531-5541. Epub 2021 Sep 3.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure.

Methods And Results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 × 10 under an additive genetic model.

Conclusions: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
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http://dx.doi.org/10.1002/ehf2.13517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712846PMC
December 2021

Empagliflozin in Heart Failure with a Preserved Ejection Fraction.

N Engl J Med 2021 10 27;385(16):1451-1461. Epub 2021 Aug 27.

From the Department of Cardiology (CVK) and the Berlin Institute of Health Center for Regenerative Therapies (BCRT), German Center for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin Berlin, Berlin (S.D.A.), Universitätsklinikum des Saarlandes, Homberg (M. Böhm), RWTH Aachen University, Aachen (N.M.), Boehringer Ingelheim Pharma, Biberach (C.Z., S.S.), Boehringer Ingelheim International, Ingelheim (W.J., M. Brueckmann), and the Faculty of Medicine Mannheim, University of Heidelberg, Mannheim (M. Brueckmann) - all in Germany; the University of Mississippi Medical Center, Jackson (J.B.); National and Kapodistrian University of Athens School of Medicine, Athens (G.F.); Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique 1433, and INSERM Unité 1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists) (J.P.F.), and Université de Lorraine, INSERM INI-CRCT, CHRU (F.Z.) - both in Nancy, France; the Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal (J.P.F.); Unidade de Insuficiência Cardíaca, Instituto do Coracao, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo (E.B.); Maastricht University Medical Center and the School for Cardiovascular Disease CARIM - both in Maastricht, the Netherlands (H.-P.B.-L.R.); the Department of Medicine, Seoul National University Bundang Hospital, Seoul, South Korea (D.-J.C.); Max Superspeciality Hospital, Saket, New Delhi, India (V.C.); the National Institute of Cardiology, Mexico City (E.C.-V.); McGill University Health Centre, Montreal (N.G.), and St. Michael's Hospital, University of Toronto, Toronto (S.V.) - both in Canada; the Cardiology Service, Fundación Valle del Lili, Universidad Icesi, Cali, Colombia (J.E.G.-M.); the Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium (S.J.); Massachusetts General Hospital and Baim Institute for Clinical Research, Boston (J.L.J.); University Hospital, Santiago de Compostela, Spain (J.R.G.-J.); Heart and Vascular Center, Semmelweiss University, Budapest, Hungary (B.M.); Victorian Heart Institute, Monash University, Melbourne, VIC, Australia (S.J.N.); Argentine Catholic University, and Medical Advisor in Heart Failure, Pulmonary Hypertension and Intrathoracic Transplant at FLENI and IADT Institute - both in Buenos Aires (S.V.P.); Central Michigan University, Mount Pleasant (I.L.P.); Wroclaw Medical University, Wroclaw, Poland (P.P.); the Cardiovascular Department, Cardiology Division, Papa Giovanni XXIII Hospital, Bergamo (M.S.), and Università di Pisa, Pisa (S.T.) - both in Italy; National Heart Centre Singapore, Singapore (D.S.); the Internal Cardiology Department, St. Ann University Hospital and Masaryk University, Brno, Czech Republic (J.S.); the University of Leicester, Glenfield General Hospital, Leicester (I.S.), the University of Glasgow, Glasgow (N.S.), the London School of Hygiene and Tropical Medicine (S.J.P.), and Imperial College, London (M.P.) - all in the United Kingdom; Kyushu University, Fukuoka, Japan (H.T.); the University of Medicine and Pharmacy, Carol Davila University and Emergency Hospital, Bucharest, Romania (D.V.); the Heart Failure Center, Fuwai Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing (J.Z.); the Veterans Affairs Medical Center, Washington, DC (P.C.); National Heart Centre Singapore, Duke-National University of Singapore, Singapore (C.S.P.L.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (J.M.S.); and Baylor Heart and Vascular Institute, Dallas (M.P.).

Background: Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain.

Methods: In this double-blind trial, we randomly assigned 5988 patients with class II-IV heart failure and an ejection fraction of more than 40% to receive empagliflozin (10 mg once daily) or placebo, in addition to usual therapy. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure.

Results: Over a median of 26.2 months, a primary outcome event occurred in 415 of 2997 patients (13.8%) in the empagliflozin group and in 511 of 2991 patients (17.1%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.69 to 0.90; P<0.001). This effect was mainly related to a lower risk of hospitalization for heart failure in the empagliflozin group. The effects of empagliflozin appeared consistent in patients with or without diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (407 with empagliflozin and 541 with placebo; hazard ratio, 0.73; 95% CI, 0.61 to 0.88; P<0.001). Uncomplicated genital and urinary tract infections and hypotension were reported more frequently with empagliflozin.

Conclusions: Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Preserved ClinicalTrials.gov number, NCT03057951).
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http://dx.doi.org/10.1056/NEJMoa2107038DOI Listing
October 2021

A Home Hospitalisation Strategy for Patients with an Acute Episode of Heart Failure Using a Digital Health-Supported Platform: A Multicentre Feasibility Study - A Rationale and Study Design.

Cardiology 2021;146(6):793-800. Epub 2021 Aug 26.

Heart Centre Hasselt, Jessa Hospital, Hasselt, Belgium.

Background: Heart failure (HF) is a common cause of hospitalisation and mortality in elderly. The frequent rehospitalisations put a serious burden on patients, health-care budgets, and health-care capacity. Frequent hospital admissions are also associated with a substantial additional hazard for serious complications and reduced quality of life. The NWE-Chance project will explore the feasibility and scalability of providing home hospitalisation supported by a newly developed digital health-supported platform and daily visits of specialised nurses.

Methods/design: Hundred patients with chronic HF will be recruited over a 1-year period. The digital health-supported home hospitalisation strategy will be tested in 3 hospitals with different experience in delivering home hospitalisation: Isala Zwolle, Maastricht UMC+, both in The Netherlands, and Jessa Hospital, Hasselt in Belgium. The home hospitalisation intervention will have a maximal duration of 14 days. Feasibility will be measured with acceptability, satisfaction, and usability questionnaires for patients, nurses, and physicians. Furthermore, safety and costs will be assessed for 30 days after the start of the home hospitalisation intervention.

Discussion: The NWE-Chance project will be one of the first studies to examine the feasibility of a digital health-supported home hospitalisation platform for HF patients. It has the potential to augment current standard HF care and quality of life of HF patients and to innovate the standard HF care to potentially lower the hospitalisation-related complications, the burden of HF on health-care systems, and to potentially implement more patient-centred care strategies.
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http://dx.doi.org/10.1159/000519085DOI Listing
December 2021

Impact of sex-specific target dose in chronic heart failure patients with reduced ejection fraction.

Eur J Prev Cardiol 2021 Aug;28(9):957-965

Department of Cardiology, University Medical Center Rotterdam, the Netherlands.

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.
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http://dx.doi.org/10.1177/2047487320923185DOI Listing
August 2021

Proteomic mechanistic profile of patients with diabetes at risk of developing heart failure: insights from the HOMAGE trial.

Cardiovasc Diabetol 2021 08 9;20(1):163. Epub 2021 Aug 9.

Department of Cardiology, Maastricht University Medical Center (MUMC+), PO Box 5800, 6202 AZ, Maastricht, The Netherlands.

Background: Patients with diabetes mellitus (DM) are at increased risk of developing heart failure (HF). The "Heart OMics in AGEing" (HOMAGE) trial suggested that spironolactone had beneficial effect on fibrosis and cardiac remodelling in an at risk population, potentially slowing the progression towards HF. We compared the proteomic profile of patients with and without diabetes among patients at risk for HF in the HOMAGE trial.

Methods: Protein biomarkers (n = 276) from the Olink®Proseek-Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline and 9 months (or last visit) from HOMAGE trial participants including 217 patients with, and 310 without, diabetes.

Results: Twenty-one biomarkers were increased and five decreased in patients with diabetes compared to non-diabetics at baseline. The markers clustered mainly within inflammatory and proteolytic pathways, with granulin as the key-hub, as revealed by knowledge-induced network and subsequent gene enrichment analysis. Treatment with spironolactone in diabetic patients did not lead to large changes in biomarkers. The effects of spironolactone on NTproBNP, fibrosis biomarkers and echocardiographic measures of diastolic function were similar in patients with and without diabetes (all interaction analyses p > 0.05).

Conclusions: Amongst patients at risk for HF, those with diabetes have higher plasma concentrations of proteins involved in inflammation and proteolysis. Diabetes does not influence the effects of spironolactone on the proteomic profile, and spironolactone produced anti-fibrotic, anti-remodelling, blood pressure and natriuretic peptide lowering effects regardless of diabetes status.  Trial registration NCT02556450.
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http://dx.doi.org/10.1186/s12933-021-01357-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351439PMC
August 2021

A global longitudinal strain cut-off value to predict adverse outcomes in individuals with a normal ejection fraction.

ESC Heart Fail 2021 10 17;8(5):4343-4345. Epub 2021 Jul 17.

Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, PO Box 5800, Maastricht, 6202 AZ, The Netherlands.

Aims: Global longitudinal strain (GLS) has become an alternative to left ventricular ejection fraction (LVEF) to determine systolic function of the heart. The absence of cut-off values is one of the limitations preventing full clinical implementation. The aim of this study is to determine a cut-off value of GLS for an increased risk of adverse events in individuals with a normal LVEF.

Methods And Results: Echocardiographic images of 502 subjects (52% female, mean age 48 ± 15) with an LVEF ≥ 55% were analysed using speckle tracking-based GLS. The primary endpoint was cardiovascular death or cardiac hospitalization. The analysis of Cox models with splines was performed to visualize the effect of GLS on outcome. A cut-off value was suggested by determining the optimal specificity and sensitivity. The median GLS was -22.2% (inter-quartile range -20.0 to -24.9%). In total, 35 subjects (7%) had a cardiac hospitalization and/or died because of cardiovascular disease during a follow-up of 40 (5-80) months. There was a linear correlation between the risk for adverse events and GLS value. Subjects with a normal LVEF and a GLS between -22.9% and -20.9% had a mildly increased risk (hazard ratio 1.01-2.0) for cardiac hospitalization or cardiovascular mortality, and the risk was doubled for subjects with a GLS of -20.9% and higher. The optimal specificity and sensitivity were determined at a GLS value of -20.0% (hazard ratio 2.49; 95% confidence interval: 1.71-3.61).

Conclusions: There is a strong correlation between cardiac adverse events and GLS values in subjects with a normal LVEF. In our single-centre study, -20.0% was determined as a cut-off value to identify subjects at risk. A next step should be to integrate GLS values in a multi-parametric model.
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http://dx.doi.org/10.1002/ehf2.13465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497344PMC
October 2021

NT-proBNP for Risk Prediction in Heart Failure: Identification of Optimal Cutoffs Across Body Mass Index Categories.

JACC Heart Fail 2021 09 7;9(9):653-663. Epub 2021 Jul 7.

Singapore General Hospital, Singapore.

Objectives: The goal of this study was to assess the predictive power of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the decision cutoffs in heart failure (HF) across body mass index (BMI) categories.

Background: Concentrations of NT-proBNP predict outcome in HF. Although the influence of BMI to reduce levels of NT-proBNP is known, the impact of obesity on prognostic value remains uncertain.

Methods: Individual data from the BIOS (Biomarkers In Heart Failure Outpatient Study) consortium were analyzed. Patients with stable HF were classified as underweight (BMI <18.5 kg/m), normal weight (BMI 18.5-24.9 kg/m), overweight (BMI 25-29.9 kg/m), and mildly (BMI 30-34.9 kg/m), moderately (BMI 35-39.9 kg/m), or severely (BMI ≥40 kg/m) obese. The prognostic role of NT-proBNP was tested for the endpoints of all-cause and cardiac death.

Results: The study population included 12,763 patients (mean age 66 ± 12 years; 25% women; mean left ventricular ejection fraction 33% ± 13%). Most patients were overweight (n = 5,176), followed by normal weight (n = 4,299), mildly obese (n = 2,157), moderately obese (n = 612), severely obese (n = 314), and underweight (n = 205). NT-proBNP inversely correlated with BMI (β = -0.174 for 1 kg/m; P < 0.001). Adding NT-proBNP to clinical models improved risk prediction across BMI categories, with the exception of severely obese patients. The best cutoffs of NT-proBNP for 5-year all-cause death prediction were lower as BMI increased (3,785 ng/L, 2,193 ng/L, 1,554 ng/L, 1,045 ng/L, 755 ng/L, and 879 ng/L, for underweight, normal weight, overweight, and mildly, moderately, and severely obese patients, respectively) and were higher in women than in men.

Conclusions: NT-proBNP maintains its independent prognostic value up to 40 kg/m BMI, and lower optimal risk-prediction cutoffs are observed in overweight and obese patients.
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http://dx.doi.org/10.1016/j.jchf.2021.05.014DOI Listing
September 2021

Determinants of acceptance of patients with heart failure and their informal caregivers regarding an interactive decision-making system: a qualitative study.

BMJ Open 2021 06 16;11(6):e046160. Epub 2021 Jun 16.

Cardiology Department, Maastricht University Medical Centre+, Maastricht, The Netherlands.

Objective: Heart failure is a growing challenge to healthcare systems worldwide. Technological solutions have the potential to improve the health of patients and help to reduce costs. Acceptability is a prerequisite for the use and a successful implementation of new disruptive technologies. This qualitative study aimed to explore determinants that influence the acceptance of patients and their informal caregivers regarding a patient-oriented digital decision-making solution-a system.

Design: We applied a semistructured design using an interview guide that was based on a theoretical framework influenced by established acceptance theories. The interviews were analysed using a content analysis.

Setting: A multicentred study in four European countries.

Participants: We interviewed 49 patients and 33 of their informal caregivers. Most of the patients were male (76%) and aged between 60 and 69 years (43%). Informal caregivers were mostly female (85%). The majority of patients (55%) suffered from heart failure with mild symptoms.

Results: Four main categories emerged from the data: and . Participants expressed clear wishes and expectations regarding a , especially the need for reassurance and support in the management of heart failure. They were receptive to changes to the current healthcare processes. However, was identified as an important basis for acceptance and use. Finally, for decision-making errors is a crucial topic in need of attention.

Conclusion: Patients and informal caregivers see clear benefits of digitalisation in healthcare. They perceive that an interactive decision-making system for patients could empower and enable effective self-care. Our results provide important insights for development processes of patient-centred decision-making systems by identifying facilitators and barriers for acceptance. Further research is needed, especially regarding the influence and mitigation of patients and informal caregivers' perceived risks.
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http://dx.doi.org/10.1136/bmjopen-2020-046160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211061PMC
June 2021

Measures of Left Ventricular Diastolic Function and Cardiorespiratory Fitness According to Glucose Metabolism Status: The Maastricht Study.

J Am Heart Assoc 2021 07 14;10(13):e020387. Epub 2021 Jun 14.

Department of Cardiology Maastricht University Medical Centre+ Maastricht The Netherlands.

Background This cross-sectional study evaluated associations between structural and functional measures of left ventricular diastolic function and cardiorespiratory fitness (CRF) in a well-characterized population-based cohort stratified according to glucose metabolism status. Methods and Results Six hundred seventy-two participants from The Maastricht Study (mean±SD age, 61±9 years; 17.4% prediabetes and 25.4% type 2 diabetes mellitus) underwent both echocardiography to determine left atrial volume index, left ventricular mass index, maximum tricuspid flow regurgitation, average e' and E/e' ratio; and submaximal cycle ergometer test to determine CRF as maximum power output per kilogram body mass. Associations were examined with linear regression adjusted for cardiovascular risk and lifestyle factors, and interaction terms. After adjustment, in normal glucose metabolism but not (pre)diabetes, higher left atrial volume index (per 1 mL/m), left ventricular mass index (per 1 g/m), maximum tricuspid regurgitation flow (per 1 m/s) were associated with higher CRF (maximum power output per kilogram body mass; β in normal glucose metabolism 0.015 [0.008-0.023], (pre)diabetes <0.10; 0.007 [-0.001 to 0.015], type 2 diabetes mellitus <0.10; 0.129 [0.011-0.246], >0.10; for left atrial volume index, left ventricular mass index, maximum tricuspid regurgitation flow, respectively). Furthermore, after adjustment, in all individuals, higher average E/e' ratio (per unit), but not average e', was associated with lower CRF (normal glucose metabolism -0.044 [-0.071 to -0.016]), >0.10). Conclusions In this population-based study, structural and functional measures of left ventricular diastolic function were independently differentially associated with CRF over the strata of glucose metabolism status. This suggests that deteriorating left ventricular diastolic function, although of small effect, may contribute to the pathophysiological process of impaired CRF in the general population. Moreover, the differential effects in these structural measures may be the consequence of cardiac structural adaptation to effectively increase CRF in normal glucose metabolism, which is absent in (pre)diabetes.
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http://dx.doi.org/10.1161/JAHA.120.020387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403322PMC
July 2021

The combination of carboxy-terminal propeptide of procollagen type I blood levels and late gadolinium enhancement at cardiac magnetic resonance provides additional prognostic information in idiopathic dilated cardiomyopathy - A multilevel assessment of myocardial fibrosis in dilated cardiomyopathy.

Eur J Heart Fail 2021 06 24;23(6):933-944. Epub 2021 Jun 24.

Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands.

Aims: To determine the prognostic value of multilevel assessment of fibrosis in dilated cardiomyopathy (DCM) patients.

Methods And Results: We quantified fibrosis in 209 DCM patients at three levels: (i) non-invasive late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR); (ii) blood biomarkers [amino-terminal propeptide of procollagen type III (PIIINP) and carboxy-terminal propeptide of procollagen type I (PICP)], (iii) invasive endomyocardial biopsy (EMB) (collagen volume fraction, CVF). Both LGE and elevated blood PICP levels, but neither PIIINP nor CVF predicted a worse outcome defined as death, heart transplantation, heart failure hospitalization, or life-threatening arrhythmias, after adjusting for known clinical predictors [adjusted hazard ratios: LGE 3.54, 95% confidence interval (CI) 1.90-6.60; P < 0.001 and PICP 1.02, 95% CI 1.01-1.03; P = 0.001]. The combination of LGE and PICP provided the highest prognostic benefit in prediction (likelihood ratio test P = 0.007) and reclassification (net reclassification index: 0.28, P = 0.02; and integrated discrimination improvement index: 0.139, P = 0.01) when added to the clinical prediction model. Moreover, patients with a combination of LGE and elevated PICP (LGE+/PICP+) had the worst prognosis (log-rank P < 0.001). RNA-sequencing and gene enrichment analysis of EMB showed an increased expression of pro-fibrotic and pro-inflammatory pathways in patients with high levels of fibrosis (LGE+/PICP+) compared to patients with low levels of fibrosis (LGE-/PICP-). This would suggest the validity of myocardial fibrosis detection by LGE and PICP, as the subsequent generated fibrotic risk profiles are associated with distinct cardiac transcriptomic profiles.

Conclusion: The combination of myocardial fibrosis at CMR and circulating PICP levels provides additive prognostic value accompanied by a pro-fibrotic and pro-inflammatory transcriptomic profile in DCM patients with LGE and elevated PICP.
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http://dx.doi.org/10.1002/ejhf.2201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362085PMC
June 2021

The bidirectional interaction between atrial fibrillation and heart failure: consequences for the management of both diseases.

Europace 2021 04;23(23 Suppl 2):ii40-ii45

Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands.

Atrial fibrillation (AF) and heart failure (HF) are both highly prevalent diseases and are accompanied by a significant disease burden and increased mortality. Although the conditions may exist independently, they often go hand in hand as each is able to provoke, sustain, and aggravate the other. In addition, the diseases share a risk profile with several coinciding cardiovascular risk factors, promoting the odds of developing both AF and HF separately from each other. When the diseases coexist, this provides additional challenges but also opportunities for the optimal treatment. The recommended management of the comorbidities has been much debated in the past decades. In this review, we describe the pathophysiological coherence of AF and HF, illustrate the current knowledge on the management of them as comorbidities of each other and look forward to future developments in this field.
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http://dx.doi.org/10.1093/europace/euaa368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035705PMC
April 2021

Spironolactone effect on the blood pressure of patients at risk of developing heart failure: an analysis from the HOMAGE trial.

Eur Heart J Cardiovasc Pharmacother 2021 Apr 2. Epub 2021 Apr 2.

Université de Lorraine, Inserm, Centre d'Investigation Clinique Plurithématique, CHRU de Nancy, F-CRIN INI-CRCT, Nancy, 1433, U1116, France.

Background: Uncontrolled blood pressure (BP) increases the risk of developing heart failure (HF). The effect of spironolactone on BP of patients at risk of developing HF is yet to be determined.

Aims: To evaluate the effect of spironolactone on the BP of patients at risk for HF and whether renin can predict spironolactone`s effect.

Methods: HOMAGE (Heart OMics in Aging) was a prospective multicenter randomized open-label blinded Endpoint (PROBE) trial including 527 patients at risk for developing HF randomly assigned to either spironolactone (25-50mg/day) or usual care alone for a maximum of 9 months. Sitting BP was assessed at baseline, month 1 and 9 (or last visit). Analysis of covariance (ANCOVA), mixed effects models, and structural modelling equations were used.

Results: The median (percentile25-75) age was 73 (69-79) years, 26% were female, and >75% had history of hypertension. Overall, the baseline BP was 142/78 mmHg. Patients with higher BP were older, more likely to have diabetes and less likely to have coronary artery disease, had greater left ventricular mass (LVM), and left atrial volume (LAV). Compared with usual care, by last visit, spironolactone changed SBP by -10.3 (-13.0 to -7.5)mmHg and DBP by -3.2 (-4.8 to -1.7)mmHg (p < 0.001 for both). A higher proportion of patients on spironolactone had controlled BP < 130/80 mmHg (36 vs. 26%; p = 0.014). Lower baseline renin levels predicted a greater response to spironolactone (interactionp=0.041).

Conclusion: Spironolactone had a clinically important BP-lowering effect. Spironolactone should be considered for lowering blood pressure in patients who are at risk of developing HF.
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http://dx.doi.org/10.1093/ehjcvp/pvab031DOI Listing
April 2021

Identification of distinct phenotypic clusters in heart failure with preserved ejection fraction.

Eur J Heart Fail 2021 06 1;23(6):973-982. Epub 2021 May 1.

Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

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.
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http://dx.doi.org/10.1002/ejhf.2169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359985PMC
June 2021

Re-appraisal of the obesity paradox in heart failure: a meta-analysis of individual data.

Clin Res Cardiol 2021 Aug 11;110(8):1280-1291. Epub 2021 Mar 11.

Department of Cardiology, Maastricht University Medical Centre, PO Box 5800, 6202AZ, Maastricht, The Netherlands.

Background: Higher body mass index (BMI) is associated with better outcome compared with normal weight in patients with HF and other chronic diseases. It remains uncertain whether the apparent protective role of obesity relates to the absence of comorbidities. Therefore, we investigated the effect of BMI on outcome in younger patients without co-morbidities as compared to older patients with co-morbidities in a large heart failure (HF) population.

Methods: In an individual patient data analysis from pooled cohorts, 5,819 patients with chronic HF and data available on BMI, co-morbidities and outcome were analysed. Patients were divided into four groups based on BMI (i.e. ≤ 18.5 kg/m, 18.5-25.0 kg/m; 25.0-30.0 kg/m; 30.0 kg/m). Primary endpoints included all-cause mortality and HF hospitalization-free survival.

Results: Mean age was 65 ± 12 years, with a majority of males (78%), ischaemic HF and HF with reduced ejection fraction. Frequency of all-cause mortality or HF hospitalization was significantly worse in the lowest two BMI groups as compared to the other two groups; however, this effect was only seen in patients older than 75 years or having at least one relevant co-morbidity, and not in younger patients with HF only. After including medications and N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin concentrations into the model, the prognostic impact of BMI was largely absent even in the elderly group with co-morbidity.

Conclusions: The present study suggests that obesity is a marker of less advanced disease, but does not have an independent protective effect in patients with chronic HF. Categories of BMI are only predictive of poor outcome in patients aged > 75 years or with at least one co-morbidity (bottom), but not in those aged < 75 years without co-morbidities (top). The prognostic effect largely disappears in multivariable analyses even for the former group. These findings question the protective effect of obesity in chronic heart failure (HF).
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http://dx.doi.org/10.1007/s00392-021-01822-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318940PMC
August 2021

Future perspective of heart failure care: benefits and bottlenecks of artificial intelligence and eHealth.

Future Cardiol 2021 Sep 12;17(6):917-921. Epub 2021 Feb 12.

Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre+ (MUMC+), Maastricht, The Netherlands.

Tweetable abstract #eHealth and #ArtificialIntelligence (AI) bring new possibilities for #HeartFailure (HF) care. We elaborate on potential benefits of #AI in #HF and highlight important bottlenecks for its implementation. #Editorial #Cardiology.
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http://dx.doi.org/10.2217/fca-2021-0008DOI Listing
September 2021

Proteomic and Mechanistic Analysis of Spironolactone in Patients at Risk for HF.

JACC Heart Fail 2021 04 3;9(4):268-277. Epub 2021 Feb 3.

Université de Lorraine, Inserm, Centre d'Investigation Clinique Plurithématique 1433, CHRU de Nancy, F-CRIN INI-CRCT, Nancy, France. Electronic address:

Objectives: This study sought to further understand the mechanisms underlying effect of spironolactone and assessed its impact on multiple plasma protein biomarkers and their respective underlying biologic pathways.

Background: In addition to their beneficial effects in established heart failure (HF), mineralocorticoid receptor antagonists may act upstream on mechanisms, preventing incident HF. In people at risk for developing HF, the HOMAGE (Heart OMics in AGEing) trial showed that spironolactone treatment could provide antifibrotic and antiremodeling effects, potentially slowing the progression to HF.

Methods: Baseline, 1-month, and 9-month (or last visit) plasma samples of HOMAGE participants were measured for protein biomarkers (n = 276) by using Olink Proseek-Multiplex cardiovascular and inflammation panels (Olink, Uppsala, Sweden). The effect of spironolactone on biomarkers was assessed by analysis of covariance and explored by knowledge-based network analysis.

Results: A total of 527 participants were enrolled; 265 were randomized to spironolactone (25 to 50 mg/day) and 262 to standard care ("control"). The median (interquartile range) age was 73 years (69 to 79 years), and 26% were female. Spironolactone reduced biomarkers of collagen metabolism (e.g., COL1A1, MMP-2); brain natriuretic peptide; and biomarkers related to metabolic processes (e.g., PAPPA), inflammation, and thrombosis (e.g., IL17A, VEGF, and urokinase). Spironolactone increased biomarkers that reflect the blockade of the mineralocorticoid receptor (e.g., renin) and increased the levels of adipokines involved in the anti-inflammatory response (e.g., RARRES2) and biomarkers of hemostasis maintenance (e.g., tPA, UPAR), myelosuppressive activity (e.g., CCL16), insulin suppression (e.g., RETN), and inflammatory regulation (e.g., IL-12B).

Conclusions: Proteomic analyses suggest that spironolactone exerts pleiotropic effects including reduction in fibrosis, inflammation, thrombosis, congestion, and vascular function improvement, all of which may mediate cardiovascular protective effects, potentially slowing progression toward heart failure. (HOMAGE [Bioprofiling Response to Mineralocorticoid Receptor Antagonists for the Prevention of Heart Failure]; NCT02556450).
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http://dx.doi.org/10.1016/j.jchf.2020.11.010DOI Listing
April 2021

Iron deficiency impacts prognosis but less exercise capacity in heart failure with preserved ejection fraction.

ESC Heart Fail 2021 04 31;8(2):1304-1313. Epub 2021 Jan 31.

Department of Cardiology, Maastricht University Medical Centre (MUMC+), PO 5800, Maastricht, 6202AZ, The Netherlands.

Aims: Whether and how iron deficiency (ID) impacts patients with heart failure (HF) with preserved ejection fraction (HFpEF) remain unclear. The aim of our study was to investigate the impact of ID on functional status, exercise capacity, and prognosis in HFpEF.

Methods And Results: The study population consisted of 300 HFpEF patients. ID was defined as serum ferritin <100 μg/L or 100-300 μg/L and transferrin-saturation <20%. Baseline functional status, quality of life (HADS score and EQ 5D index), 6 min walking test, echocardiography, and outcome (all-cause mortality and combined all cause-mortality and HF hospitalization) were evaluated. ID was found in 159 (53%) patients. Patients with ID had a worse prognosis with a higher combined endpoint of all-cause mortality and HF hospitalization after 4 years of follow-up (log rank = 0.008). Pulmonary hypertension, depression, and thyroid disease were more prevalent in the ID group. Multivariable analysis showed that ID was independently associated with body mass index (P = 0.003), pulmonary hypertension (P = 0.008), and thyroid disease (P = 0.01). Although patients with ID had a lower exercise capacity compared with patients without ID (393 m [294-455] vs. 344 m [260-441], P = 0.008), there was no significant correlation after multivariable correction for age, BMI, NT-proBNP, DM, and depression.

Conclusions: Heart failure with preserved ejection fraction patients with ID have a worse prognosis and impaired exercise capacity compared with those without ID. However, although a trend was observed, after multivariable correction ID was no longer significantly associated with a reduced exercise capacity. This reflects that impaired exercise capacity in HFpEF is complex and seems multifactorial. Interestingly, pulmonary hypertension was an independent predictor of both ID and exercise capacity.
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http://dx.doi.org/10.1002/ehf2.13204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006701PMC
April 2021
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