Publications by authors named "Wilfried Mullens"

200 Publications

Why mechanical dyssynchrony remains relevant to cardiac resynchronization therapy: Reply.

Eur J Heart Fail 2021 Mar 31. Epub 2021 Mar 31.

Imperial College London, Royal Brompton Hospital, London, UK.

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http://dx.doi.org/10.1002/ejhf.2180DOI Listing
March 2021

The management of secondary mitral regurgitation in patients with heart failure: a joint position statement from the Heart Failure Association (HFA), European Association of Cardiovascular Imaging (EACVI), European Heart Rhythm Association (EHRA), and European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC.

Eur Heart J 2021 Mar 18. Epub 2021 Mar 18.

Department of Cardiology, St Thomas' Hospital, Westminster Bridge Road, London, UK.

Secondary (or functional) mitral regurgitation (SMR) occurs frequently in chronic heart failure (HF) with reduced left ventricular (LV) ejection fraction, resulting from LV remodelling that prevents coaptation of the valve leaflets. Secondary mitral regurgitation contributes to progression of the symptoms and signs of HF and confers worse prognosis. The management of HF patients with SMR is complex and requires timely referral to a multidisciplinary Heart Team. Optimization of pharmacological and device therapy according to guideline recommendations is crucial. Further management requires careful clinical and imaging assessment, addressing the anatomical and functional features of the mitral valve and left ventricle, overall HF status, and relevant comorbidities. Evidence concerning surgical correction of SMR is sparse and it is doubtful whether this approach improves prognosis. Transcatheter repair has emerged as a promising alternative, but the conflicting results of current randomized trials require careful interpretation. This collaborative position statement, developed by four key associations of the European Society of Cardiology-the Heart Failure Association (HFA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association of Cardiovascular Imaging (EACVI), and European Heart Rhythm Association (EHRA)-presents an updated practical approach to the evaluation and management of patients with HF and SMR based upon a Heart Team approach.
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http://dx.doi.org/10.1093/eurheartj/ehab086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014526PMC
March 2021

Diuretic response and effects of diuretic omission in ambulatory heart failure patients on chronic low-dose loop diuretic therapy.

Eur J Heart Fail 2021 Feb 28. Epub 2021 Feb 28.

Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium.

Aims: To study loop diuretic response and effect of loop diuretic omission in ambulatory heart failure (HF) patients on chronic low-dose loop diuretics.

Methods And Results: Urine collections were performed on two consecutive days in 40 ambulatory HF patients with 40-80 mg furosemide (day 1 with loop diuretic; day 2 without loop diuretic). Three phases were collected each day: (i) first 6 h; (ii) rest of the day; and (iii) night. On the day of loop diuretic intake, the total natriuresis was 125.9 (86.9-155.0) mmol/24 h and urine output was 1650 (1380-2025) mL/24 h. There was a clear loop diuretic response with a natriuresis of 9.4 (6.7-15.9) mmol/h and a urine output of 117 (83-167) mL/h during the first 6 h, followed by a significant drop in natriuresis and urine output during the rest of the day [2.6 (1.8-4.8) mmol/h and 55 (33-71) mL/h] and night [2.2 (1.6-3.5) mmol/h and 44 (34-73) mL/h]. On day 2, after loop diuretic omission, the natriuresis and urine output remained similarly low the entire day, resulting in a 50% reduction in natriuresis [55.1 (33.5-77.7) mmol/24 h; P < 0.001] and a 31% reduction in urine output [1035 (875-1425) mL/24 h; P < 0.001] compared with the day of loop diuretic intake.

Conclusion: Patients with HF on chronic loop diuretic treatment still have a clear diuretic response phase, while loop diuretic omission leads to a significant drop in natriuresis and urine output, arguing against routine cessation of low-dose loop diuretics.
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http://dx.doi.org/10.1002/ejhf.2145DOI Listing
February 2021

Impact of Cardiac Resynchronization Therapy on Global and Cardiac Metabolism and Cardiac Mitochondrial Function.

J Card Fail 2021 Feb 24. Epub 2021 Feb 24.

Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium; Department of Laboratory Medicine, KU Leuven, UZ Leuven, Leuven, Belgium; Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.

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http://dx.doi.org/10.1016/j.cardfail.2021.02.008DOI Listing
February 2021

The value of urinary sodium assessment in acute heart failure.

Eur Heart J Acute Cardiovasc Care 2021 Apr;10(2):216-223

Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium.

Acute heart failure (AHF) is a frequent medical condition that needs immediate evaluation and appropriate treatment. Patients with signs and symptoms of volume overload mostly require intravenous loop diuretics in the first hours of hospitalization. Some patients may develop diuretic resistance, resulting in insufficient and delayed decongestion, with increased mortality and morbidity. Urinary sodium measurement at baseline and/or during treatment has been proposed as a useful parameter to tailor diuretic therapy in these patients. This systematic review discusses the current sum of evidence regarding urinary sodium assessment to evaluate diuretic efficacy in AHF. We searched Medline, Embase, and Cochrane Clinical Trials Register for published studies that tested urinary sodium assessment in patients with AHF.
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http://dx.doi.org/10.1093/ehjacc/zuaa006DOI Listing
April 2021

The FAST-FURO study: effect of very early administration of intravenous furosemide in the prehospital setting to patients with acute heart failure attending the emergency department.

Eur Heart J Acute Cardiovasc Care 2021 Jan 18. Epub 2021 Jan 18.

The GREAT (Global REsearch in Acute cardiovascular conditions Team) Network, Madrid, Spain.

Aims: The effect of early administration of intravenous (IV) furosemide in the emergency department (ED) on short-term outcomes of acute heart failure (AHF) patients remains controversial, with one recent Japanese study reporting a decrease of in-hospital mortality and one Korean study reporting a lack of clinical benefit. Both studies excluded patients receiving prehospital IV furosemide and only included patients requiring hospitalization. To assess the impact on short-term outcomes of early IV furosemide administration by emergency medical services (EMS) before patient arrival to the ED.

Methods And Results: In a secondary analysis of the Epidemiology of Acute Heart Failure in Emergency Departments (EAHFE) registry of consecutive AHF patients admitted to Spanish EDs, patients treated with IV furosemide at the ED were classified according to whether they received IV furosemide from the EMS (FAST-FURO group) or not (CONTROL group). In-hospital all-cause mortality, 30-day all-cause mortality, and prolonged hospitalization (>10 days) were assessed. We included 12 595 patients (FAST-FURO = 683; CONTROL = 11 912): 968 died during index hospitalization [7.7%; FAST-FURO = 10.3% vs. CONTROL = 7.5%; odds ratio (OR) = 1.403, 95% confidence interval (95% CI) = 1.085-1.813; P = 0.009], 1269 died during the first 30 days (10.2%; FAST-FURO = 13.4% vs. CONTROL = 9.9%; OR = 1.403, 95% CI = 1.146-1.764; P = 0.004), and 2844 had prolonged hospitalization (22.8%; FAST-FURO = 25.8% vs. CONTROL = 22.6%; OR = 1.189, 95% CI = 0.995-1.419; P = 0.056). FAST-FURO group patients had more diabetes mellitus, ischaemic cardiomyopathy, peripheral artery disease, left ventricular systolic dysfunction, and severe decompensations, and had a better New York Heart Association class and had less atrial fibrillation. After adjusting for these significant differences, early IV furosemide resulted in no impact on short-term outcomes: OR = 1.080 (95% CI = 0.817-1.427) for in-hospital mortality, OR = 1.086 (95% CI = 0.845-1.396) for 30-day mortality, and OR = 1.095 (95% CI = 0.915-1.312) for prolonged hospitalization. Several sensitivity analyses, including analysis of 599 pairs of patients matched by propensity score, showed consistent findings.

Conclusion: Early IV furosemide during the prehospital phase was administered to the sickest patients, was not associated with changes in short-term mortality or length of hospitalization after adjustment for several confounders.
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http://dx.doi.org/10.1093/ehjacc/zuaa042DOI Listing
January 2021

Optimized Implementation of cardiac resynchronization therapy - a call for action for referral and optimization of care.

Europace 2021 Feb 5. Epub 2021 Feb 5.

Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.

Cardiac resynchronization therapy (CRT) is one of the most effective therapies for heart failure with reduced ejection fraction and leads to improved quality of life, reductions in heartfailure hospitalization rates and reduces all-cause mortality. Nevertheless, up to two-thirds ofeligible patients are not referred for CRT. Furthermore, post implantation follow-up is oftenfragmented and suboptimal, hampering the potential maximal treatment effect. This jointposition statement from three ESC Associations, HFA, EHRA and EACVI focuses onoptimized implementation of CRT. We offer theoretical and practical strategies to achievemore comprehensive CRT referral and post-procedural care by focusing on four actionabledomains; (I) overcoming CRT under-utilization, (II) better understanding of pre-implantcharacteristics, (III) abandoning the term 'non-response' and replacing this by the concept ofdisease modification, and (IV) implementing a dedicated post-implant CRT care pathway.
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http://dx.doi.org/10.1093/europace/euab035DOI Listing
February 2021

Empagliflozin and renal sodium handling: an intriguing smart osmotic diuretic.

Eur J Heart Fail 2021 Jan 7;23(1):79-82. Epub 2021 Jan 7.

Ziekenhuis Oost Limburg, Genk, Belgium.

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http://dx.doi.org/10.1002/ejhf.2086DOI Listing
January 2021

Optimized implementation of cardiac resynchronization therapy: a call for action for referral and optimization of care: A joint position statement from the Heart Failure Association (HFA), European Heart Rhythm Association (EHRA), and European Association of Cardiovascular Imaging (EACVI) of the European Society of Cardiology.

Eur J Heart Fail 2020 12;22(12):2349-2369

Cardiologie, CHU Rennes - LTSI Inserm UMR 1099, Université Rennes-1, Rennes, France.

Cardiac resynchronization therapy (CRT) is one of the most effective therapies for heart failure with reduced ejection fraction and leads to improved quality of life, reductions in heart failure hospitalization rates and all-cause mortality. Nevertheless, up to two-thirds of eligible patients are not referred for CRT. Furthermore, post-implantation follow-up is often fragmented and suboptimal, hampering the potential maximal treatment effect. This joint position statement from three European Society of Cardiology Associations, Heart Failure Association (HFA), European Heart Rhythm Association (EHRA) and European Association of Cardiovascular Imaging (EACVI), focuses on optimized implementation of CRT. We offer theoretical and practical strategies to achieve more comprehensive CRT referral and post-procedural care by focusing on four actionable domains: (i) overcoming CRT under-utilization, (ii) better understanding of pre-implant characteristics, (iii) abandoning the term 'non-response' and replacing this by the concept of disease modification, and (iv) implementing a dedicated post-implant CRT care pathway.
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http://dx.doi.org/10.1002/ejhf.2046DOI Listing
December 2020

Ultrasound imaging of congestion in heart failure: examinations beyond the heart.

Eur J Heart Fail 2020 Oct 29. Epub 2020 Oct 29.

Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique, INSERM 1433, CHRU de Nancy, Institut Lorrain du Coeur et des Vaisseaux, Nancy, France.

Congestion, related to pressure and/or fluid overload, plays a central role in the pathophysiology, presentation and prognosis of heart failure and is an important therapeutic target. While symptoms and physical signs of fluid overload are required to make a clinical diagnosis of heart failure, they lack both sensitivity and specificity, which might lead to diagnostic delay and uncertainty. Over the last decades, new ultrasound methods for the detection of elevated intracardiac pressures and/or fluid overload have been developed that are more sensitive and specific, thereby enabling earlier and more accurate diagnosis and facilitating treatment strategies. Accordingly, we considered that a state-of-the-art review of ultrasound methods for the detection and quantification of congestion was timely, including imaging of the heart, lungs (B-lines), kidneys (intrarenal venous flow), and venous system (inferior vena cava and internal jugular vein diameter).
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http://dx.doi.org/10.1002/ejhf.2032DOI Listing
October 2020

Heart Failure Association of the European Society of Cardiology update on sodium-glucose co-transporter 2 inhibitors in heart failure.

Eur J Heart Fail 2020 11 27;22(11):1984-1986. Epub 2020 Oct 27.

Department of Medical Sciences, IRCCS San Raffaele Pisana, Rome, Italy.

The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) has recently issued a position paper on the role of sodium-glucose co-transporter 2 (SGLT2) inhibitors in heart failure (HF). The present document provides an update of the position paper, based of new clinical trial evidence. Accordingly, the following recommendations are given: • Canagliflozin, dapagliflozin empagliflozin, or ertugliflozin are recommended for the prevention of HF hospitalization in patients with type 2 diabetes mellitus and established cardiovascular disease or at high cardiovascular risk. • Dapagliflozin or empagliflozin are recommended to reduce the combined risk of HF hospitalization and cardiovascular death in symptomatic patients with HF and reduced ejection fraction already receiving guideline-directed medical therapy regardless of the presence of type 2 diabetes mellitus.
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http://dx.doi.org/10.1002/ejhf.2026DOI Listing
November 2020

Economic implications of adding a novel algorithm to optimize cardiac resynchronization therapy: rationale and design of economic analysis for the AdaptResponse trial.

J Med Econ 2020 Dec 28;23(12):1401-1408. Epub 2020 Oct 28.

Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, OH, USA.

Aims: Although cardiac resynchronization therapy (CRT) has proven beneficial in several randomized trials, a subset of patients have limited clinical improvement. The AdaptivCRT algorithm provides automated selection between synchronized left ventricular or biventricular pacing with optimization of atrioventricular delays. The rationale and design of the economic analysis of the AdaptResponse clinical trial are described.

Rationale: The costs associated with HF hospitalization are substantial and are compounded by a high rate of readmission. HF hospitalization payments range from $1,001 for Greece to $12,235 for US private insurance. When examining the breakdown of HF-related costs, it is clear that approximately 55% of the hospitalization costs are directly attributable to length of stay. Notably, the mean costs of a CRT patient in need of a HF-related hospitalization are currently estimated to be an average of $10,679.

Methods: The economic analysis of the AdaptResponse trial has two main objectives. The hospital provider objective seeks to test the hypothesis that AdaptivCRT reduces the incidence of all-cause re-admissions after a heart failure admission within 30 days of the index event. A negative binomial regression model will be used to estimate and compare the number of readmissions after an index HF hospitalization. The payer economic objective will assess cost-effectiveness of CRT devices with the AdaptivCRT algorithm relative to traditional CRT programming. This analysis will be conducted from a U.S. payer perspective. A decision analytic model comprised of a 6-month decision tree and a Markov model for long term extrapolation will be used to evaluate lifetime costs and benefits.

Conclusion: AdaptivCRT may offer improvements over traditional device programming in patient outcomes. How the data from AdaptResponse will be used to demonstrate if these clinical benefits translate into substantial economic gains is herein described.
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http://dx.doi.org/10.1080/13696998.2020.1835333DOI Listing
December 2020

Impact of an extended audit on identifying heart failure patients in general practice: baseline results of the OSCAR-HF pilot study.

ESC Heart Fail 2020 Sep 24. Epub 2020 Sep 24.

Department of Cardiovascular Diseases, Universitair Ziekenhuis Gasthuisberg, KU Leuven (KUL), Leuven, Belgium.

Aims: Identifying heart failure (HF) patients in general practice is challenging, and little is known about the current quality of care. We implemented an extended audit from the electronic health records (EHRs) of general practitioners (GPs) to identify HF patients and investigate patient characteristics and quality of care.

Methods And Results: This study describes the baseline results of the OSCAR-HF pilot study in eight general practices (51 GPs) in Flanders, Belgium. This prospective trial ran for 6 months. Interventions included an extended audit, an N-terminal pro-B-type natriuretic peptide point-of-care test, and assistance of a specialist HF nurse. The extended audit searched on risk factors for HF, HF symptoms, signs, and medication in the GPs' EHR to generate a list of possible HF patients. GPs determined which patients had HF. Those HF patients constituted the OSCAR-HF study population. Each patient file was manually revised to extract biomarker measurements, echocardiography data, and quality indicators. An independent panel of experts assessed the validity of GPs' HF diagnoses. Feedback about the validity of the HF diagnosis was given to the GP. Out of 18 011 patients ≥ 40 years, we identified 310 patients with a registered HF diagnosis before the study start (HF prevalence: 1.7%). The extended audit led to a 74% increase in identified HF patients (n = 538, HF prevalence: 3.0%) with a mean age of 79 ± 11 years. The prevalence of HF with reduced ejection fraction (HFrEF) was 20% (n = 110). A high proportion of patients underwent echocardiography in the past 5 years (86%, n = 462). Natriuretic peptides were rarely available in patients' files (19%, n = 100). Medical specialists should improve communication about the HF diagnosis because a specialist diagnosis was present in only 225 patients (42%) while 67% (n = 359) of the HF diagnoses were judged objectified by a panel of experts. Assigning a diagnosis of HF was particularly difficult in HF patients with preserved EF (HFpEF). HFrEF treatment rates with renin-angiotensin-aldosterone system blockers (84%, n = 92) and beta-blockers (86%, n = 94) were very good; however, target doses were hardly reached (34% and 14%, respectively).

Conclusions: This study highlighted the need to improve case finding for HF in general practice and showed that an extended audit in the GPs' EHR was a successful strategy to do so. To improve the quality of HF care in general practice, specific strategies are needed to diagnose HFpEF and to reach target doses of disease-modifying drugs in HFrEF patients.
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http://dx.doi.org/10.1002/ehf2.12990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754725PMC
September 2020

Self-care of heart failure patients: practical management recommendations from the Heart Failure Association of the European Society of Cardiology.

Eur J Heart Fail 2021 Jan 20;23(1):157-174. Epub 2020 Oct 20.

Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.

Self-care is essential in the long-term management of chronic heart failure. Heart failure guidelines stress the importance of patient education on treatment adherence, lifestyle changes, symptom monitoring and adequate response to possible deterioration. Self-care is related to medical and person-centred outcomes in patients with heart failure such as better quality of life as well as lower mortality and readmission rates. Although guidelines give general direction for self-care advice, health care professionals working with patients with heart failure need more specific recommendations. The aim of the management recommendations in this paper is to provide practical advice for health professionals delivering care to patients with heart failure. Recommendations for nutrition, physical activity, medication adherence, psychological status, sleep, leisure and travel, smoking, immunization and preventing infections, symptom monitoring, and symptom management are consistent with information from guidelines, expert consensus documents, recent evidence and expert opinion.
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http://dx.doi.org/10.1002/ejhf.2008DOI Listing
January 2021

The Effect of Decongestion on Intrarenal Venous Flow Patterns in Patients With Acute Heart Failure.

J Card Fail 2021 Jan 11;27(1):29-34. Epub 2020 Sep 11.

Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium; Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium. Electronic address:

Background: Discontinuous intrarenal venous flow patterns, as assessed by renal Doppler ultrasound examination, are associated with changes in hemodynamics such as volume expansion and poorer diuretic response in patients with heart failure (HF). We aimed to study intrarenal venous and arterial flow patterns after decongestive treatment in patients with acute HF.

Methods And Results: Fifteen patients with acute HF were enrolled. Intrarenal venous and arterial flow patterns were assessed at baseline, 1 hour after administration of loop diuretics, at day 2 and day 3. Among patients hospitalized for acute HF, 13 (87%) had a discontinuous venous flow pattern at admission. After decongestive treatment, a significant improvement of the venous impedance index (P = .021) and venous discontinuity index (P = .004) was observed at day 3 compared with baseline. There was no effect on the intrarenal arterial flow patterns.

Conclusions: In patients who exhibit discontinuous renal venous flow patterns hospitalized for decongestive treatment owing to acute HF led to a normalization of intrarenal venous flow to a continuous pattern.
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http://dx.doi.org/10.1016/j.cardfail.2020.09.003DOI Listing
January 2021

Differences in clinical characteristics and reported quality of life of men and women undergoing cardiac resynchronization therapy.

ESC Heart Fail 2020 10 13;7(5):2972-2982. Epub 2020 Aug 13.

School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Aims: Response to cardiac resynchronization therapy (CRT) is known to be associated with a number of clinical characteristics, including QRS duration and morphology, gender, height, and the aetiology of heart failure (HF). We assessed the relation of gender and baseline characteristics with QRS duration and Kansas City Cardiomyopathy Questionnaire.

Methods And Results: AdaptResponse is a global randomized trial. The trial enrolled CRT-indicated patients with New York Heart Association classes II-IV HF, left bundle branch block (QRS ≥ 140 ms in men, ≥130 ms in women), and baseline PR interval ≤200 ms. In total, 3620 patients were randomized, including 1569 women (43.3%) approaching the actual proportion of women in the HF population. Women were older and more often New York Heart Association class III or IV than men (55.6% vs. 48.7%), had less frequent ischaemic cardiomyopathy (21.2% vs. 39.5%), and had a 5.1 ms shorter QRS duration than men. Women were more often depressed (18.5% vs. 9.7%), had a significantly lower Kansas City Cardiomyopathy Questionnaire score, and had differences in medication prescriptions.

Conclusions: AdaptResponse is the largest randomized CRT trial and enrolled more women than any other landmark CRT trial. Women differed from men with regard to baseline characteristics and quality of life. Whether these differences translate into clinical outcome differences will be examined further in the AdaptResponse trial.
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http://dx.doi.org/10.1002/ehf2.12914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524066PMC
October 2020

Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: a position statement on behalf of the Heart Failure Association (HFA), the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the European Society of Cardiology (ESC).

Eur J Heart Fail 2020 09 21;22(9):1504-1524. Epub 2020 Aug 21.

National Heart and Lung Institute, Imperial College, London, UK.

Cardiovascular (CV) imaging is an important tool in baseline risk assessment and detection of CV disease in oncology patients receiving cardiotoxic cancer therapies. This position statement examines the role of echocardiography, cardiac magnetic resonance, nuclear cardiac imaging and computed tomography in the management of cancer patients. The Imaging and Cardio-Oncology Study Groups of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the ESC have evaluated the current evidence for the value of modern CV imaging in the cardio-oncology field. The most relevant echocardiographic parameters, including global longitudinal strain and three-dimensional ejection fraction, are proposed. The protocol for baseline pre-treatment evaluation and specific surveillance algorithms or pathways for anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor tyrosine kinase inhibitors, BCr-Abl tyrosine kinase inhibitors, proteasome inhibitors and immune checkpoint inhibitors are presented. The indications for CV imaging after completion of oncology treatment are considered. The typical consequences of radiation therapy and the possibility of their identification in the long term are also summarized. Special populations are discussed including female survivors planning pregnancy, patients with carcinoid disease, patients with cardiac tumours and patients with right heart failure. Future directions and ongoing CV imaging research in cardio-oncology are discussed.
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http://dx.doi.org/10.1002/ejhf.1957DOI Listing
September 2020

Sodium-glucose co-transporter 2 inhibitors in heart failure: beyond glycaemic control. A position paper of the Heart Failure Association of the European Society of Cardiology.

Eur J Heart Fail 2020 09 5;22(9):1495-1503. Epub 2020 Aug 5.

Department of Medical Sciences, IRCCS San Raffaele Pisana, Rome, Italy.

Heart failure (HF) is common and associated with a poor prognosis, despite advances in treatment. Over the last decade cardiovascular outcome trials with sodium-glucose co-transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus have demonstrated beneficial effects for three SGLT2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) in reducing hospitalisations for HF. More recently, dapagliflozin reduced the risk of worsening HF or death from cardiovascular causes in patients with chronic HF with reduced left ventricular ejection fraction, with or without type 2 diabetes mellitus. A number of additional trials in HF patients with reduced and/or preserved left ventricular ejection fraction are ongoing and/or about to be reported. The present position paper summarises recent clinical trial evidence and discusses the role of SGLT2 inhibitors in the treatment of HF, pending the results of ongoing trials in different populations of patients with HF.
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http://dx.doi.org/10.1002/ejhf.1954DOI Listing
September 2020

Effects of dapagliflozin on congestion assessed by remote pulmonary artery pressure monitoring.

ESC Heart Fail 2020 10 26;7(5):2071-2073. Epub 2020 Jun 26.

Department of Cardiology, Ziekenhuis Oost Limburg, Genk, Belgium.

Aims: To explore the effects of dapagliflozin on congestion through CardioMEMS (Abbott Inc., Atlanta, USA) and Cordella™ pulmonary artery Sensor (Endotronix Inc., Lisle, Il, USA) devices, which are implantable systems that provide real-time remote monitoring of pulmonary artery pressure (PAP).

Methods And Results: Single-centre open label observational pilot trial, to investigate the short-term effects of dapagliflozin in consecutive heart failure and reduced ejection fraction patients with elevated PAP between October and December 2019, previously implanted with CardioMEMS or Cordella™ Sensor. Changes in PAP were evaluated with an area under the curve methodology to estimate the total sum increase or decrease in pressures (mmHg/day) for 7 days before and after starting dapagliflozin relative to the first day of each period. Nine patients (72 ± 10 years, N-terminal pro b-type natriuretic peptide 1027 ± 510 pg/mL, estimated glomerular filtration rate 45 ± 15 mL/kg/m2, left ventricular ejection fraction 35 ± 10%), all on optimal guideline-directed therapy was included. The mean PAP was reduced from 42 ± 9.16 to 38 ± 9.95 mmHg with dapagliflozin therapy (P < 0.05). The average area under the curve for the week leading to dapagliflozin therapy remained unchanged compared to the drop observed for the week after therapy (P < 0.05). Interestingly, the drop in PAP occurred within the first 2 days of dapagliflozin and remained stable for the week following the start of the therapy.

Conclusions: This is the first study to demonstrate a direct effect of dapagliflozin on achieving effective hemodynamic decongestion, providing further mechanistic data regarding the potential mechanisms of sodium-glucose co-transporter-2 inhibitor benefits on heart failure.
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http://dx.doi.org/10.1002/ehf2.12850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524114PMC
October 2020

Heart failure is associated with accelerated age related metabolic bone disease.

Acta Cardiol 2020 Jun 5:1-9. Epub 2020 Jun 5.

Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium.

The heart failure (HF)-syndrome is associated with neuro-hormonal activation, chronic kidney disease (CKD), inflammation and alterations in the phosphorus-metabolism, all of which are involved in regulation of mineral bone density. However, the role of HF as an independent factor associated with metabolic bone disease (MBD) remains unclear. HF-patients undergoing dual X-ray absorptiometry (DEXA) were matched in a 1:2 fashion against age and gender matched controls without HF, to determine the proportion of osteoporosis (T-score < -2.5). HF-status was tested against known predictors of MBD. Correlation analysis and Z-score analysis were used to assess the impact of HF on age-related bone demineralisation. A total of 190 HF-patients (age = 80 ± 10 years, female = 61%) were age and gender matched to 380 controls. HF-patients had a higher proportion of osteoporosis (26 vs 17%;  = .007). HF patients had a lower averaged mineral bone density expressed in g/cm ( = .030), T-scores ( = .001) and Z-scores ( < .001). After adjusting for the individual osteoporosis risk-factors of the FRAX-score, difference in baseline features, kidney function and phosphorus-metabolism alterations, heart failure remained independently associated with a lower averaged T-score (Adjusted = -0.189;  = .017). Heart failure was associated with an accelerated age-related decline in mineral bone density ( = .0418). Therapies with ACE-I or ARBs and beta-blockers associated with ameliorated bone demineralisation ( = .023, respectively  = .029), while loop diuretic associated with worsened bone demineralization ( < .001). Heart failure independently associates with MBD and higher prevalence of osteoporosis. Heart failure aggravates the aged related loss in mineral bone density while treatment with neuro-hormonal blockers seemed to ameliorate this finding.
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http://dx.doi.org/10.1080/00015385.2020.1771885DOI Listing
June 2020

Impact of Sacubitril-Valsartan on Markers of Glomerular Function.

Curr Heart Fail Rep 2020 08;17(4):145-152

Department of Cardiology, Ziekenhuis Oost-Limburg, Schiepse Bos 6, 3600, Genk, Belgium.

Purpose Of Review: To provide pathophysiological and clinical insights into the effects of sacubitril/valsartan on glomerular function.

Recent Findings: Heart failure and glomerular dysfunction are closely intertwined. In addition to reduced heart failure hospitalization and all-cause mortality, patients treated with sacubitril/valsartan have a slower deterioration of glomerular filtration rate over time compared with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. The effects of sacubitril/valsartan are probably mediated through enhancement of natriuretic peptides, reduction of glomerular inflammation and fibrosis, and relaxation of mesangial cells and podocytes. Further studies will elucidate underlying pathophysiological mechanisms of sacubitril/valsartan on glomerular function and their prognostic significance in subjects with and without heart failure.
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http://dx.doi.org/10.1007/s11897-020-00463-1DOI Listing
August 2020

Digital health care solution for proactive heart failure management with the Cordella Heart Failure System: results of the SIRONA first-in-human study.

Eur J Heart Fail 2020 10 31;22(10):1912-1919. Epub 2020 May 31.

The Lambe Institute for Translational Medicine and CURAM, National University of Ireland Galway, Galway, Ireland.

Aims: Incorporation of remote monitoring of pulmonary artery pressure and vital signs has been demonstrated to reduce heart failure (HF) hospitalization and all-cause mortality in selected symptomatic HF patients. The aim of this study is to investigate the safety and accuracy of the new Cordella Pulmonary Artery Pressure Sensor (Endotronix, Inc., Chicago, IL, USA) and the usability of the comprehensive Cordella Heart Failure System (CHFS).

Methods And Results: Multicentre, open-label, first-in-human, feasibility study to evaluate the CHFS and the safety and accuracy of the Cordella™ Pulmonary Artery Pressure Sensor in 15 patients with New York Heart Association class III HF. All patients were successfully implanted with the Cordella Pulmonary Artery Pressure Sensor, without sensor failure. No device system-related complications, defined as invasive treatment, device explant or death, occurred. The primary efficacy endpoint of a mean pulmonary artery pressure at 90 days was met in all but one patients with a cohort difference of 2.7 mmHg (Cordella Sensor 22.5 ± 11.8 mmHg, Swan-Ganz catheter 25.2 ± 8.5 mmHg). One patient did not go through the 90-day right heart catheterization for safety reasons. Patient adherence to daily measurement, transmission of vital signs and pulmonary artery pressure sensor readings were recorded 99% of the time.

Conclusion: The initial experience of the CHFS incorporating comprehensive vital signs and pulmonary artery pressure monitoring enables safe and accurate monitoring of HF status.
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http://dx.doi.org/10.1002/ejhf.1870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687200PMC
October 2020

Epidemiology, pathophysiology and contemporary management of cardiogenic shock - a position statement from the Heart Failure Association of the European Society of Cardiology.

Eur J Heart Fail 2020 08 16;22(8):1315-1341. Epub 2020 Jul 16.

Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Cardiogenic shock (CS) is a complex multifactorial clinical syndrome with extremely high mortality, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ failure and death. There is a large spectrum of CS presentations resulting from the interaction between an acute cardiac insult and a patient's underlying cardiac and overall medical condition. Phenotyping patients with CS may have clinical impact on management because classification would support initiation of appropriate therapies. CS management should consider appropriate organization of the health care services, and therapies must be given to the appropriately selected patients, in a timely manner, whilst avoiding iatrogenic harm. Although several consensus-driven algorithms have been proposed, CS management remains challenging and substantial investments in research and development have not yielded proof of efficacy and safety for most of the therapies tested, and outcome in this condition remains poor. Future studies should consider the identification of the new pathophysiological targets, and high-quality translational research should facilitate incorporation of more targeted interventions in clinical research protocols, aimed to improve individual patient outcomes. Designing outcome clinical trials in CS remains particularly challenging in this critical and very costly scenario in cardiology, but information from these trials is imperiously needed to better inform the guidelines and clinical practice. The goal of this review is to summarize the current knowledge concerning the definition, epidemiology, underlying causes, pathophysiology and management of CS based on important lessons from clinical trials and registries, with a focus on improving in-hospital management.
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http://dx.doi.org/10.1002/ejhf.1922DOI Listing
August 2020

Acute coronary syndromes and acute heart failure: a diagnostic dilemma and high-risk combination. A statement from the Acute Heart Failure Committee of the Heart Failure Association of the European Society of Cardiology.

Eur J Heart Fail 2020 08 29;22(8):1298-1314. Epub 2020 Apr 29.

Department of Cardiology, Cumhuriyet University Faculty of Medicine, Sivas, Turkey.

Acute coronary syndrome is a precipitant of acute heart failure in a substantial proportion of cases, and the presence of both conditions is associated with a higher risk of short-term mortality compared to acute coronary syndrome alone. The diagnosis of acute coronary syndrome in the setting of acute heart failure can be challenging. Patients may present with atypical or absent chest pain, electrocardiograms can be confounded by pre-existing abnormalities, and cardiac biomarkers are frequently elevated in patients with chronic or acute heart failure, independently of acute coronary syndrome. It is important to distinguish transient or limited myocardial injury from primary myocardial infarction due to vascular events in patients presenting with acute heart failure. This paper outlines various clinical scenarios to help differentiate between these conditions and aims to provide clinicians with tools to aid in the recognition of acute coronary syndrome as a cause of acute heart failure. Interpretation of electrocardiogram and biomarker findings, and imaging techniques that may be helpful in the diagnostic work-up are described. Guidelines recommend an immediate invasive strategy for patients with acute heart failure and acute coronary syndrome, regardless of electrocardiographic or biomarker findings. Pharmacological management of patients with acute coronary syndrome and acute heart failure should follow guidelines for each of these syndromes, with priority given to time-sensitive therapies for both. Studies conducted specifically in patients with the combination of acute coronary syndrome and acute heart failure are needed to better define the management of these patients.
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http://dx.doi.org/10.1002/ejhf.1831DOI Listing
August 2020

Improved cardiac and venous pressures during hospital stay in patients with acute heart failure: an echocardiography and biomarkers study.

ESC Heart Fail 2020 06 11;7(3):996-1006. Epub 2020 Apr 11.

Inserm UMR-S 942, Paris, France.

Aims: Changes in echocardiographic parameters and biomarkers of cardiac and venous pressures or estimated plasma volume during hospitalization associated with decongestive treatments in acute heart failure (AHF) patients with either preserved left ventricular ejection fraction (LVEF) (HFPEF) or reduced LVEF (HFREF) are poorly assessed.

Methods And Results: From the metabolic road to diastolic heart failure: diastolic heart failure (MEDIA-DHF) study, 111 patients were included in this substudy: 77 AHF (43 HFPEF and 34 HFREF) and 34 non-cardiac dyspnea patients. Echocardiographic measurements and blood samples were obtained within 4 h of presentation at the emergency department and before hospital discharge. In AHF patients, echocardiographic indices of cardiac and venous pressures, including inferior vena cava diameter [from 22 (16-24) mm to 13 (11-18) mm, P = 0.009], its respiratory variability [from 32 (8-44) % to 43 (29-70) %, P = 0.04], medial E/e' [from 21.1 (15.8-29.6) to 16.6 (11.7-24.3), P = 0.004], and E wave deceleration time [from 129 (105-156) ms to 166 (128-203) ms, P = 0.003], improved during hospitalization, similarly in HFPEF and HFREF patients. By contrast, no changes were seen in non-cardiac dyspnea patients. In AHF patients, all plasma biomarkers of cardiac and venous pressures, namely B-type natriuretic peptide [from 935 (514-2037) pg/mL to 308 (183-609) pg/mL, P < 0.001], mid-regional pro-atrial natriuretic peptide [from 449 (274-653) pmol/L to 366 (242-549) pmol/L, P < 0.001], and soluble CD-146 levels [from 528 (406-654) ng/mL to 450 (374-529) ng/mL, P = 0.003], significantly decreased during hospitalization, similarly in HFPEF and HFREF patients. Echocardiographic parameters of cardiac chamber dimensions [left ventricular end-diastolic volume: from 120 (76-140) mL to 118 (95-176) mL, P = 0.23] and cardiac index [from 2.1 (1.6-2.6) mL/min/m to 1.9 (1.4-2.4) mL/min/m , P = 0.55] were unchanged in AHF patients, except tricuspid annular plane systolic excursion (TAPSE) that improved during hospitalization [from 16 (15-19) mm to 19 (17-21) mm, P = 0.04]. Estimated plasma volume increased in both AHF [from 4.8 (4.2-5.6) to 5.1 (4.4-5.8), P = 0.03] and non-cardiac dyspnea patients (P = 0.01). Serum creatinine [from 1.18 (0.90-1.53) to 1.19 (0.86-1.70) mg/dL, P = 0.89] and creatinine-based estimated glomerular filtration rate [from 59 (40-75) mL/min/1.73m to 56 (38-73) mL/min/1.73m , P = 0.09] were similar, while plasma cystatin C [from 1.50 (1.20-2.27) mg/L to 1.78 (1.33-2.59) mg/L, P < 0.001] and neutrophil gelatinase associated lipocalin (NGAL) [from 127 (95-260) ng/mL to 167 (104-263) ng/mL, P = 0.004] increased during hospitalization in AHF.

Conclusions: Echocardiographic parameters and plasma biomarkers of cardiac and venous pressures improved during AHF hospitalization in both acute HFPEF and HFREF patients, while cardiac chamber dimensions, cardiac output, and estimated plasma volume showed minimal changes.
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http://dx.doi.org/10.1002/ehf2.12645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261539PMC
June 2020

The importance of developing hyperkalaemia in heart failure during long-term follow-up.

Acta Cardiol 2020 Apr 8:1-9. Epub 2020 Apr 8.

Doctoral School for Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.

Hyperkalaemia is a potentially life-threatening condition. Furthermore, it is one of the main reasons for discontinuation and dose reduction of renin-angiotensin-aldosterone system inhibitors (RAASi) in clinical practice. However, exact data on the prevalence and consequences of occurrence of hyperkalaemia when taking RAASi in a dedicated heart failure care setting are scarce. Consecutive patients diagnosed with heart failure from a single tertiary hospital between August 2000 and May 2017 were retrospectively evaluated. Primary endpoint was the development of hyperkalaemia (≥5.5 mmol/L) at any moment during follow-up. About 396 patients were included in the current analysis (mean follow-up 6.9 years). 26% ( = 104) and 12% ( = 46) of patients developed hyperkalaemia (≥5.5 mmol/L and ≥6.0 mmol/L, respectively). Diabetes mellitus (OR = 1.80, 95% CI = 1.03-3.19) and baseline creatinine (mg/dL) (OR = 2.37, 95% CI = 2.37-3.85) were independent risk factors for hyperkalaemia. Development of hyperkalaemia was associated with 6.5 higher odds for recurrence. Only 10% developed hyperkalaemia during up-titration of RAASi, while 90% developed during later follow-up on stable doses of RAASi. hyperkalaemia was not associated with worse outcome after multivariate adjustment for baseline co-morbidities. However, hyperkalaemia was associated with discontinuation and lower doses of MRAs during follow-up ( = 0.007). Discontinuation of MRA due to hyperkalaemia was associated with an increase in all-cause mortality in HFrEF patients (HR = 1.77, 95% CI = 1.05-2.99). Approximately, one-fourth of patients developed hyperkalaemia during follow-up which was associated with a lower MRA dose during follow-up. Discontinuation of MRA, but not hyperkalaemia itself, was associated with an increased risk of all-cause mortality and heart failure admission in HFrEF patients.
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http://dx.doi.org/10.1080/00015385.2020.1748346DOI Listing
April 2020

Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry.

Eur J Heart Fail 2020 08 1;22(8):1424-1437. Epub 2020 Apr 1.

Unit of Cardiology, Department of Medicine, Karolinska Institutet, and Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden.

Aims: Guidelines recommend down-titration of loop diuretics (LD) once euvolaemia is achieved. In outpatients with heart failure (HF), we investigated LD dose changes in daily cardiology practice, agreement with guideline recommendations, predictors of successful LD down-titration and association between dose changes and outcomes.

Methods And Results: We included 8130 HF patients from the ESC-EORP Heart Failure Long-Term Registry. Among patients who had dose decreased, successful decrease was defined as the decrease not followed by death, HF hospitalization, New York Heart Association class deterioration, or subsequent increase in LD dose. Mean age was 66 ± 13 years, 71% men, 62% HF with reduced ejection fraction, 19% HF with mid-range ejection fraction, 19% HF with preserved ejection fraction. Median [interquartile range (IQR)] LD dose was 40 (25-80) mg. LD dose was increased in 16%, decreased in 8.3% and unchanged in 76%. Median (IQR) follow-up was 372 (363-419) days. Diuretic dose increase (vs. no change) was associated with HF death [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.12-2.08; P = 0.008] and nominally with cardiovascular death (HR 1.25, 95% CI 0.96-1.63; P = 0.103). Decrease of diuretic dose (vs. no change) was associated with nominally lower HF (HR 0.59, 95% CI 0.33-1.07; P = 0.083) and cardiovascular mortality (HR 0.62, 95% CI 0.38-1.00; P = 0.052). Among patients who had LD dose decreased, systolic blood pressure [odds ratio (OR) 1.11 per 10 mmHg increase, 95% CI 1.01-1.22; P = 0.032], and absence of (i) sleep apnoea (OR 0.24, 95% CI 0.09-0.69; P = 0.008), (ii) peripheral congestion (OR 0.48, 95% CI 0.29-0.80; P = 0.005), and (iii) moderate/severe mitral regurgitation (OR 0.57, 95% CI 0.37-0.87; P = 0.008) were independently associated with successful decrease.

Conclusion: Diuretic dose was unchanged in 76% and decreased in 8.3% of outpatients with chronic HF. LD dose increase was associated with worse outcomes, while the LD dose decrease group showed a trend for better outcomes compared with the no-change group. Higher systolic blood pressure, and absence of (i) sleep apnoea, (ii) peripheral congestion, and (iii) moderate/severe mitral regurgitation were independently associated with successful dose decrease.
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http://dx.doi.org/10.1002/ejhf.1796DOI Listing
August 2020

Withdrawal of Neurohumoral Blockade After Cardiac Resynchronization Therapy.

J Am Coll Cardiol 2020 03;75(12):1426-1438

Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium; Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium. Electronic address:

Background: The necessity of neurohumoral blockers in patients with heart failure who demonstrate normalized ejection fractions after cardiac resynchronization therapy remains unclear.

Objectives: The aim of this study was to investigate the feasibility and safety of neurohumoral blocker withdrawal in patients with normalized ejection fractions after cardiac resynchronization therapy.

Methods: In this prospective, open-label, randomized controlled pilot trial with a 2 × 2 factorial design, subjects were randomized to withdrawal of renin-angiotensin-aldosterone system inhibitors and/or beta-blockers versus continuation of treatment. The primary endpoint was a recurrence of negative remodeling, defined as an increase in left ventricular end-systolic volume index of >15% at 24 months. The secondary endpoint was a composite safety endpoint of all-cause mortality, heart failure-related hospitalizations, and incidence of sustained ventricular arrhythmias at 24 months.

Results: Eighty subjects were consecutively enrolled and randomized among 4 groups (continuation of neurohumoral blocker therapy, n = 20; withdrawal of renin-angiotensin-aldosterone system inhibitors, n = 20; withdrawal of beta-blockers, n = 20; and withdrawal of renin-angiotensin-aldosterone system inhibitors and beta-blockers, n = 20). Of the 80 subjects, 6 (7.5%) met the primary and 4 (5%) the secondary endpoint. However, re-initiation of neurohumoral blockers occurred in 17 subjects because of hypertension or supraventricular arrhythmias.

Conclusions: The incidence of the primary and secondary endpoints over a follow-up period of 2 years was low in both the control group and in the groups in which neurohumoral blockers were discontinued. However, neurohumoral blocker withdrawal was hampered by cardiac comorbidities. (Systematic Withdrawal of Neurohumoral Blocker Therapy in Optimally Responding CRT Patients [STOP-CRT]; NCT02200822).
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http://dx.doi.org/10.1016/j.jacc.2020.01.040DOI Listing
March 2020