Publications by authors named "Pieter Martens"

82 Publications

Iron deficiency is associated with impaired biventricular reserve and reduced exercise capacity in patients with unexplained dyspnea.

J Card Fail 2021 Apr 7. Epub 2021 Apr 7.

Department of Cardiology, Hartcentrum, Jessa Hospital, Hasselt, Belgium; Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.

Background: Iron deficiency (ID) is frequent and associated with diminished exercise capacity in heart failure (HF), but its contribution to unexplained dyspnea without a HF diagnosis at rest remains unclear.

Methods: Consecutive patients with unexplained dyspnea and normal echocardiography and pulmonary function tests at rest underwent prospective standardized cardiopulmonary exercise testing with echocardiography (CPETecho) in a tertiary care dyspnea clinic. ID was defined as ferritin <300µg/l and transferrin saturation (TSAT)<20% and its impact on peak oxygen uptake (peakVO), biventricular response to exercise, and peripheral oxygen extraction was assessed.

Results: Of 272 CPETecho patients, 63 (23%) had ID. For a similar respiratory exchange ratio, patients with ID had lower peakVO (14.6±7.6 vs 17.8±8.8ml/kg/min; p=0.009) and maximal workload (89±50 vs 108±56 watt p=0.047), even after adjustment for the presence of anemia. At rest, patients with ID had a similar left ventricular and right ventricular (RV) contractile function. During exercise, patients with ID had lower cardiac output reserve (p<0.05) and depressed RV function by tricuspid s' (p=0.004), tricuspid annular plane systolic excursion (TAPSE; p=0.034) and RV end-systolic pressure-area ratio (RVESPAR; p=0.038), with more RV-pulmonary artery uncoupling measured by TAPSE/systolic pulmonary arterial pressure ratio (p=0.023). RVESPAR change from rest to peak exercise, as a load-insensitive metric of RV contractility, was lower in patients with ID (2.09±0.72 vs. 2.58±1.14 mmHg/cm; p<0.001). ID was associated with impaired peripheral oxygen extraction (peakVO/peak cardiac output; p=0.036). CPETecho resulted in a diagnosis of HF with preserved ejection fraction in 71 patients (26%) based on an exercise E/e' ratio above 14, with equal distribution in patients with (28.6%) or without ID (25.4%, p=0.611). None of the aforementioned findings were influenced in a sensitivity analysis adjusted for a final diagnosis of HFpEF as etiology for the unexplained dyspnea.

Conclusion: In patients with unexplained dyspnea without clear HF at rest, ID is common and associated with reduced exercise capacity, diminished biventricular contractile reserve and reduced peripheral oxygen extraction.
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http://dx.doi.org/10.1016/j.cardfail.2021.03.010DOI Listing
April 2021

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

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

Iron deficiency in heart failure-time to redefine.

Eur J Prev Cardiol 2020 Nov 25. Epub 2020 Nov 25.

Department of Cardiology, University Medical Center Groningen, University of Groningen, Hazenplein 1, Groningen, The Netherlands.

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http://dx.doi.org/10.1093/eurjpc/zwaa119DOI Listing
November 2020

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

Ultrafiltration in Acute Heart Failure: Implications of Ejection Fraction and Early Response to Treatment From CARRESS-HF.

J Am Heart Assoc 2020 12 8;9(24):e015752. Epub 2020 Dec 8.

Division of Cardiology Duke University Medical Center Durham NC.

Background Ultrafiltration is not commonly used because of higher incidence of worsening renal function without improved decongestion. We examined differential outcomes of high versus low fluid removal and preserved versus reduced ejection fraction (EF) in CARRESS-HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure). Methods and Results Baseline characteristics in the ultrafiltration arm were compared according to 24-hour ultrafiltration-based fluid removal above versus below the median. Patients were stratified by EF (≤40% or >40%). We compared clinical parameters of clinical decongestion during the hospitalization based on initial (≤24 hours) response to ultrafiltration. Cox-proportional hazards models were used to identify associations between fluid removal <24 hours and composite of death, hospitalization, or unscheduled outpatient/emergency department visit during study follow-up. The intention-to-treat analysis included 93 patients. Within 24 hours, median fluid removal was 1.89 L (Q1, Q3: 1.22, 3.16). The high fluid removal group had a greater urine output (9.08 versus 6.23 L, =0.027) after 96 hours. Creatinine change from baseline to 96 hours was similar in both groups (0.10 mg/dL increase, =0.610). The EF >40% group demonstrated larger increases of change in creatinine (=0.023) and aldosterone (=0.038) from baseline to 96 hours. Among patients with EF >40%, those with above median fluid removal (n=17) when compared with below median (n=17) had an increased rate of the combined end point (87.5% versus 47.1%, =0.014). Conclusions In patients with acute heart failure, higher initial fluid removal with ultrafiltration had no association with worsening renal function. In patients with EF >40%, ultrafiltration was associated with worsening renal function irrespective of fluid removal rate and higher initial fluid removal was associated with higher rates of adverse clinical outcomes, highlighting variable responses to decongestive therapy.
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http://dx.doi.org/10.1161/JAHA.119.015752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955382PMC
December 2020

Association of Visit-to-Visit Variability in Kidney Function and Serum Electrolyte Indexes With Risk of Adverse Clinical Outcomes Among Patients With Heart Failure With Preserved Ejection Fraction.

JAMA Cardiol 2021 Jan;6(1):68-77

Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas.

Importance: Although kidney dysfunction and abnormalities in serum electrolyte levels are associated with poor clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF), the association of visit-to-visit variability in such laboratory measures with long-term outcomes is unclear.

Objective: To evaluate the associations of visit-to-visit variability in indexes of kidney function (creatinine and blood urea nitrogen [BUN] levels) and serum electrolyte (sodium, chloride, and potassium) with the risk of adverse clinical outcomes among patients with chronic, stable HFpEF.

Design, Setting, And Participants: This cohort analysis used data from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. All participants with 3 or more serial laboratory measurements who were event free within the first 4 months of enrollment were included. Data were analyzed from March 1, 2019, to January 31, 2020.

Main Outcomes And Measures: Adjusted associations between indexes of variability in serum laboratory measurements during the first 4 months of follow-up and risk of the primary composite outcome (a composite of aborted cardiac arrest, hospitalization for heart failure, or cardiovascular death) and all-cause mortality were assessed using Cox proportional hazards regression models.

Results: Of the 3445 patients enrolled in the TOPCAT trial (mean [SD] age, 68-69 [10] years; 49.7%-51.5% female), 2479 (BUN) to 3195 (potassium) were analyzed, depending on availability of serial measurements. Participants with higher laboratory variability in kidney function parameters were older, had more comorbidities, and had more severe symptoms of HFpEF. Higher visit-to-visit variability in BUN (hazard ratio [HR] per 1-SD higher average successive variability [ASV], 1.21; 95% CI, 1.10-1.33) and creatinine (HR per 1-SD higher ASV, 1.13; 95% CI, 1.04-1.22) were independently associated with a higher risk of the primary composite outcome as well as mortality independent of other baseline confounders, changes in kidney function, changes in medication dosages, and variability in other cardiometabolic parameters (systolic blood pressure and body mass index). The higher risk associated with greater variability in kidney function was consistent across subgroups of patients stratified by the presence of chronic kidney disease (CKD) at baseline (CKD: HR per 1-SD higher ASV, 1.39; 95% CI, 1.16-1.67 and no CKD: HR per 1-SD higher ASV, 1.13; 95% CI, 1.01-1.27), among placebo and spironolactone treatment arms separately (spironolactone arm: 1.30; 95% CI, 1.03-1.65 and placebo arm: HR per 1-SD higher ASV, 1.27; 95% CI, 1.04-1.56). Among serum electrolytes, variability in sodium and potassium measures were also significantly associated with a higher risk of primary composite events (sodium: HR per 1-SD higher ASV, 1.14; 95% CI, 1.01-1.30 and potassium: HR per 1-SD higher ASV, 1.21; 95% CI, 1.02-1.44).

Conclusions And Relevance: In HFpEF, visit-to-visit variability in laboratory indexes of kidney function and serum electrolytes is common and independently associated with worse long-term clinical outcomes.
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http://dx.doi.org/10.1001/jamacardio.2020.5592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675220PMC
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

Measures of Loop Diuretic Efficiency and Prognosis in Chronic Kidney Disease.

Cardiorenal Med 2020 29;10(6):402-414. Epub 2020 Oct 29.

Department of Nephrology, Dialysis and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium.

Background: The evolution and prognostic impact of loop diuretic efficiency according to chronic kidney disease (CKD) severity is unclear.

Methods: This retrospective cohort study includes 783 CKD patients on oral loop diuretic therapy with a 24-h urine collection available. Acute kidney injury and history of renal replacement therapy were exclusion criteria. Patients were stratified according to Kidney Disease Improving Global Outcomes (KDIGO) glomerular filtration rate class. Loop diuretic efficiency was calculated as urine output, natriuresis, and chloruresis, each adjusted for loop diuretic dose, and compared among strata. Risk for onset of dialysis and all-cause mortality was evaluated.

Results: Loop diuretic efficiency metrics decreased from KDIGO class IIIB to IV in furosemide users and from KDIGO class IV to V with all loop diuretics (p value <0.05 for all comparisons). The correlation between loop diuretic efficiency and creatinine clearance was moderate at best (Spearman's ρ 0.298-0.436; p value <0.001 for all correlations). During median follow-up of 45 months, 457 patients died (58%) and 63 received kidney transplantation (8%), while dialysis was started before in 328 (42%). All loop diuretic efficiency metrics were significantly and independently associated with both the risk for dialysis and all-cause mortality. In KDIGO class IV/V patients, low loop diuretic efficiency (i.e., urine output adjusted for loop diuretic dose ≤1,000 mL) shortened median time to dialysis with 24 months and median time to all-cause mortality with 23 months.

Conclusion: Low loop diuretic efficiency is independently associated with a shorter time to dialysis initiation and a higher risk for all-cause mortality in CKD.
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http://dx.doi.org/10.1159/000509741DOI Listing
October 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

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

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

The in- and out-of-hospital management of HF patients: results from a nationwide Belgian survey.

Acta Cardiol 2020 Jun 8:1-10. Epub 2020 Jun 8.

Novartis Pharma NV-SA, Vilvoorde, Belgium.

We conducted a nationwide survey to describe the in-and out-of-hospital flow (diagnosis, treatment and follow-up) of patients with heart failure with reduced ejection fraction (HFrEF). A survey was developed with five dedicated HF cardiologists. The data are all self-reported by cardiologists. The response rate was 84%. Presence of a dedicated HF cardiologist or HF nurse was indicated by 49% and 46% of the hospitals respectively. Devices ( < .05), angiotensin receptor neprilysin inhibitors, and rehabilitation are considered more standard of care therapy by dedicated compared to non-dedicated HF cardiologists. Most cardiologists indicated that target dosages of HF drugs can be reached in 25‒75% of patients. Achieving >75% of the target dose seems easier for angiotensin converting enzyme inhibitor/angiotensin receptor blockers (ACEI/ARB) (22%) and mineralocorticoid receptor antagonists (25%), compared to β-blockers (10%) and angiotensin receptor neprilysin inhibitors (7%). 62%, 49% and 4% of the cardiologists indicated to use subtypes of angiotensin converting enzyme inhibitors, angiotensin receptor blockers and β-blockers respectively not validated in the HF population. In the acute setting, dedicated HF cardiologists (23%) are less influenced by blood parameters for decongestion compared to non-dedicated HF cardiologists (39%). They tend to change patients more to guideline-recommended drugs (60% vs 47%). Six minutes walk test and ergospirometry are significantly more used by dedicated compared to non-dedicated HF cardiologists for HF drug change (17% and 29% vs 2% and 4%). This survey showed that a minority of hospitals have HF care. Those that do, report a higher implementation of guideline-recommended diagnosis, treatment and follow-up of HF patients. Competent authorities could use this survey as a tool to improve HF care.
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http://dx.doi.org/10.1080/00015385.2020.1765105DOI Listing
June 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

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

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

Cardiovascular Volume Reserve in Patients with Heart Failure and Reduced Ejection Fraction.

J Cardiovasc Transl Res 2020 08 25;13(4):519-527. Epub 2020 Feb 25.

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

This study aimed to investigate the relationship between intravascular volume and intracardiac filling pressures in stable HF patients with reduced ejection fraction (HFrEF). A total of 40 HFrEF patients (LVEF 36 ± 10%) (10 subjects with a pulmonary artery catheter) underwent intravascular volume expansion with 1 L hydroxyl-ethyl-starch over 3 h with coinciding intravascular volume measurements (technetium (99 tc)-labeled red blood cell technique). Intravascular blood volume increased from 5.0 ± 1.0 L to 5.7 ± 1.0 L (p < 0.0001). No change in clinical status, echocardiographic indices, or cardiac filling pressures was noticed. Invasively measured right atrial pressure and pulmonary arterial wedge pressure increased significantly immediately after start of infusion (4 ± 2 mmHg to 8 ± 4 mmHg; p = 0.01 and 10 ± 3 mmHg to 15 ± 6 mmHg; p = 0.01, respectively), decreased afterwards, and remained stable for 3 h (6 ± 2 mmHg and 14 ± 4 mmHg, respectively). The accuracy of cardiac filling pressure estimates to predict intravascular volume expansion was low (all AUC < 0.65).
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http://dx.doi.org/10.1007/s12265-020-09973-8DOI Listing
August 2020

Higher doses of loop diuretics limit uptitration of angiotensin-converting enzyme inhibitors in patients with heart failure and reduced ejection fraction.

Clin Res Cardiol 2020 Aug 30;109(8):1048-1059. Epub 2020 Jan 30.

Ziekenhuis Oost-Limburg, Genk, Belgium.

Background: Loop diuretics are frequently prescribed to patients with heart failure and reduced ejection fraction (HFrEF) for the treatment of congestion; however, they might hamper uptitration of inhibitors of the renin-angiotensin system.

Methods: Loop diuretic dose at baseline was recorded in 2338 patients with HFrEF enrolled in BIOSTAT-CHF, an international study of HF patients on loop diuretic therapy who were eligible for uptitration of angiotensin-converting enzyme inhibitors (ACEi)/mineralocorticoid receptor antagonists (MRA). The association between loop diuretic dose and uptitration of ACEi/MRA to percentage of target dose was adjusted for a previously published model for likelihood of uptitration and a propensity score.

Results: Baseline median loop diuretic dose was 40 [40-100] mg of furosemide or equivalent. Higher doses of loop diuretics were associated with higher NYHA class and higher levels of NT-proBNP, more severe signs and symptoms of congestion, more frequent MRA use, and lower doses of ACEi reached at 3 and 9 months (all P < 0.01). After propensity adjustment, higher doses of loop diuretics remained significantly associated with poorer uptitration of ACEi (Beta per log doubling of loop diuretic dose: - 1.66, P = 0.021), but not with uptitration of MRAs (P = 0.758). Higher doses of loop diuretics were independently associated with an increased risk of all-cause mortality or HF hospitalization [HR per doubling of loop diuretic dose: 1.06 (1.01-1.12), P = 0.021].

Conclusions: Higher doses of loop diuretics limited uptitration of ACEi in patients with HFrEF and were associated with a higher risk of death and/or HF hospitalization, independent of their lower likelihood of uptitration and higher baseline risk. This figure was created with images adapted from Servier Medical Art licensed under a Creative Commons Attribution 3.0.
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http://dx.doi.org/10.1007/s00392-020-01598-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375987PMC
August 2020

LA Mechanics in Decompensated Heart Failure: Insights From Strain Echocardiography With Invasive Hemodynamics.

JACC Cardiovasc Imaging 2020 05 15;13(5):1107-1115. Epub 2020 Jan 15.

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

Objectives: The aim of this study was to assess the effect of congestion and decongestive therapy on left atrial (LA) mechanics and to determine the relationship between LA improvement after decongestive therapy and clinical outcome in immediate or chronic heart failure with reduced ejection fraction (HFrEF).

Background: LA mechanics are affected by volume/pressure overload in decompensated HFrEF.

Methods: A total of 31 patients with HFrEF and immediate heart failure (age 64 ± 15 years, 74% male, left ventricular ejection fraction 20 ± 12%) underwent serial echocardiography during decongestive therapy with simultaneous hemodynamic monitoring. LA function was assessed by strain (rate) imaging. Patients were re-evaluated 6 weeks after discharge and prospectively followed up for the composite endpoint of heart failure readmission and all-cause mortality.

Results: LA reservoir function was markedly reduced at baseline and improved with decongestion (peak atrial longitudinal strain from 6.4 ± 2.2% to 8.8 ± 3.0% and strain rate from 0.29 ± 0.11 s to 0.38 ± 0.13 s), independent of changes in left ventricular global longitudinal strain, LA end-diastolic volume, and mitral regurgitation severity (p < 0.001). Both measures continued to rise at 6 weeks (up to 13.4 ± 6.1% and 0.50 ± 0.19 s, respectively; p < 0.001). LA pump strain rate only increased 6 weeks after discharge (-0.25 ± 0.12 s to -0.55 ± 0.29 s; p < 0.010). Changes in LA mechanics correlated with changes in wedge pressure (r = -0.61; p < 0.001). Lower peak atrial longitudinal strain values after decongestion were associated with increased risk for the composite endpoint of heart failure and mortality (p < 0.019).

Conclusions: LA reservoir and booster function, while severely impaired during immediate decompensation, significantly improve during and after decongestive therapy. Poor LA reservoir function after decongestion is associated with worse outcome.
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http://dx.doi.org/10.1016/j.jcmg.2019.12.008DOI Listing
May 2020

Evaluation of kidney function throughout the heart failure trajectory - a position statement from the Heart Failure Association of the European Society of Cardiology.

Eur J Heart Fail 2020 04 7;22(4):584-603. Epub 2020 Jan 7.

IRCCS, San Raffaele Pisana, Rome, Italy.

Appropriate interpretation of changes in markers of kidney function is essential during the treatment of acute and chronic heart failure. Historically, kidney function was primarily assessed by serum creatinine and the calculation of estimated glomerular filtration rate. An increase in serum creatinine, also termed worsening renal function, commonly occurs in patients with heart failure, especially during acute heart failure episodes. Even though worsening renal function is associated with worse outcome on a population level, the interpretation of such changes within the appropriate clinical context helps to correctly assess risk and determine further treatment strategies. Additionally, it is becoming increasingly recognized that assessment of kidney function is more than just glomerular filtration rate alone. As such, a better evaluation of sodium and water handling by the renal tubules allows to determine the efficiency of loop diuretics (loop diuretic response and efficiency). Also, though neurohumoral blockers may induce modest deteriorations in glomerular filtration rate, their use is associated with improved long-term outcome. Therefore, a better understanding of the role of cardio-renal interactions in heart failure in symptom development, disease progression and prognosis is essential. Indeed, perhaps even misinterpretation of kidney function is a leading cause of not attaining decongestion in acute heart failure and insufficient dosing of guideline-directed medical therapy in general. This position paper of the Heart Failure Association Working Group on Cardio-Renal Dysfunction aims at improving insights into the interpretation of renal function assessment in the different heart failure states, with the goal of improving heart failure care.
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http://dx.doi.org/10.1002/ejhf.1697DOI Listing
April 2020

Determinants of maximal dose titration of sacubitril/valsartan in clinical practice.

Acta Cardiol 2021 Feb 7;76(1):20-29. Epub 2019 Nov 7.

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

Background: Little information is available about the tolerability of uptitration to the maximal dose of sacubitril/valsartan and the predictors and clinical correlates of achieving such a dose.

Methods: All consecutive heart failure patients with reduced ejection fraction (HFrEF) who received sacubitril/valsartan for a class-IB indication in a tertiary heart failure clinic were retrospectively analysed. Predictors of maximal uptitration including associated changes in clinical parameters were assessed in patients with at least 1 follow-up.

Results: A total of 401 HFrEF-patients received sacubitril/valsartan. Uptitration was possible in 41% and up to 32% of patients tolerated the maximal dose of sacubitril/valsartan. Younger age (HR = 0.862; CI = 0.751-0.989), higher systolic-blood-pressure (HR = 1.077; CI = 1.014-1.137), lower serum creatinine (HR = 0.064; CI = 0.005-0.822), and higher previous dose of renin-angiotensin-system-inhibitors (RASi [HR = 1.065; CI = 1.016-1.115]) independently predicted a higher odds of tolerating a maximal dose of sacubitril/valsartan. Patients who were seen more frequently in a structured heart failure clinic were also more likely to receive a maximal dose ( .038). Patient assigned to the maximal dose, were more often able to reduce their loop diuretic dose ( .001) and more often had an increase in serum creatinine ( .011), without a higher risk for hyperkalemia ( .524). An improvement in New York Heart Association class and the rate of heart failure hospitalisations was observed in all patients, independent of the sacubitril/valsartan dose.

Conclusion: Uptitration to the maximal dose of sacubitril/valsartan is possible in up to 32% of real-world HFrEF-patients in our cohort, which relates to both patient characteristics' as well as heart failure care-related factors.
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http://dx.doi.org/10.1080/00015385.2019.1686226DOI Listing
February 2021

Rationale and design of the IRON-CRT trial: effect of intravenous ferric carboxymaltose on reverse remodelling following cardiac resynchronization therapy.

ESC Heart Fail 2019 12 28;6(6):1208-1215. Epub 2019 Sep 28.

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

Aims: Iron deficiency is common in heart failure with reduced ejection fraction (HFrEF). In patients with cardiac resynchronization therapy (CRT), it is associated with a diminished reverse remodelling response and poor functional improvement. The latter is partially related to a loss in contractile force at higher heart rates (negative force-frequency relationship).

Methods And Results: The effect of intravenous ferric carboxymaltose on reverse remodelling following cardiac resynchronization therapy (IRON-CRT) trial is a multicentre, prospective, randomized, double-blind controlled trial in HFrEF patients who experienced incomplete reverse remodelling (defined as a left ventricular ejection fraction below <45%) at least 6 months after CRT. Additionally, patients need to have iron deficiency defined as a ferritin below 100 μg/L irrespective of transferrin saturation or a ferritin between 100 and 300 μg/L with a transferrin saturation <20%. Patients will be randomized to either intravenous ferric carboxymaltose (dose based according to Summary of Product Characteristics) or intravenous placebo. The primary objective is to evaluate the effect of ferric carboxymaltose on metrics of cardiac reverse remodelling and contractility, measured by the primary endpoint, change in left ventricular ejection fraction assessed by three-dimensional (3D) echo from baseline to 3 month follow-up and the secondary endpoints change in left ventricular end-systolic and end-diastolic volume. The secondary objective is to determine if ferric carboxymaltose is capable of improving cardiac contractility in vivo, by assessing the force-frequency relationship through incremental biventricular pacing. A total of 100 patients will be randomized in a 1:1 fashion.

Conclusions: The IRON-CRT trial will determine the effect of ferric carboxymaltose on cardiac reverse remodelling and rate-dependent cardiac contractility in HFrEF patients.
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http://dx.doi.org/10.1002/ehf2.12503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989286PMC
December 2019

CRT Optimization: What Is New? What Is Necessary?

Curr Treat Options Cardiovasc Med 2019 Jul 25;21(9):45. Epub 2019 Jul 25.

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

Cardiac resynchronization therapy (CRT) has proven to improve quality of life, reduce heart failure hospitalization, and prolong life in selected heart failure patients with reduced ejection fraction, on optimal medical therapy and with electrical dyssynchrony. To ensure maximal benefit for CRT patients, optimization of care should be implemented. This begins with appropriate referring as well as selecting patients, knowing that the presence of left bundle branch block and QRS ≥ 150 ms is associated with the greatest reverse remodeling. The LV lead, preferably quadripolar, is best targeted in a postero-lateral position. After implantation, optimal device programming should aim for maximal biventricular pacing and in selected cases further electrical delay optimization might be of use. Even as important, is the implementation of thorough multidisciplinary heart failure care with medication uptitration, remote monitoring, rehabilitation, and patient education. The role of newer pacing strategies as endocardial or His-bundle pacing remains the subject of ongoing investigation.
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http://dx.doi.org/10.1007/s11936-019-0751-2DOI Listing
July 2019

The Detrimental Effect of RA Pacing on LA Function and Clinical Outcome in Cardiac Resynchronization Therapy.

JACC Cardiovasc Imaging 2020 04 17;13(4):895-906. Epub 2019 Jul 17.

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

Objectives: This study assessed the impact of right-atrial (RA) pacing on left-atrial (LA) physiology and clinical outcome.

Background: Data for the effects of RA pacing on LA synchronicity, function, and structure after cardiac resynchronization therapy (CRT) are scarce.

Methods: The effect of RA pacing on LA function, morphology, and synchronicity was assessed in a prospective imaging cohort of heart failure (HF) patients in sinus rhythm with a guideline-based indication for CRT. Additionally, in a retrospective outcome cohort of consecutive HF patients undergoing CRT implantation, the relationship to RA pacing was assessed using various outcome endpoints. High versus low atrial pacing burden was defined as atrial pacing above or below 50% in both cohorts.

Results: A total of 36 patients were included in the imaging cohort (68 ± 11 years of age). Six months after CRT, patients with high RA pacing burden showed less improvement in LA maximum and minimum volumes and total emptying fraction (p < 0.05). Peak atrial longitudinal strain and reservoir and booster strain rates but not conduit strain rate improved after CRT in patients with low RA pacing burden but worsened in patients with high RA pacing burden (p < 0.05 for all). A high RA pacing burden induced significant intra-atrial dyssynchrony (maximum opposing wall delay: 44 ± 13 ms vs. 97 ± 17 ms, respectively; p = 0.022). A total of 569 patients were included in the outcome cohort. After covariate adjustments were made, a high RA pacing burden was associated with reduced LV reverse remodeling (β = 8.738; 95% confidence interval [CI]: 3.101 to 14.374; p = 0.002) and new-onset or recurrent atrial fibrillation (41% vs. 22%, respectively, at a median of 31 months [range 22 to 44 months follow-up]; p < 0.001). There were no differences in time to first HF hospitalization or all-cause mortality (p = 0.185) after covariate adjustment. However, in a recurrent event analysis, HF readmissions were more common in patients exposed to a high RA pacing burden (p = 0.003).

Conclusions: RA pacing in CRT patients negatively influences LA morphology, function, and synchronicity, which is associated with worse clinical outcome, including diminished LV reverse remodeling, increased risk for new-onset or recurrent AF and heart failure readmission. Strategies reducing RA pacing burden may be warranted.
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http://dx.doi.org/10.1016/j.jcmg.2019.04.022DOI Listing
April 2020

Response to Cardiac Resynchronization Therapy Across Chronic Kidney Disease Stages.

J Card Fail 2019 Oct 16;25(10):803-811. Epub 2019 Jul 16.

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

Introduction: Limited data are available concerning the effect of severe chronic kidney disease (CKD) on the response to cardiac resynchronization therapy (CRT) because these patients are commonly excluded from trials. Therefore, we aimed to assess the effect of CRT on renal function, reverse remodeling and outcome across all stages of CKD in a large patient population of recipients of CRT.

Methods: We retrospectively evaluated 798 consecutive patients with heart failure who were undergoing CRT implantation between October 2008 and September 2016. Renal function data were available at baseline and at 6 months following CRT. Remodeling based on left ventricular end diastolic volume/left ventricular ejection fraction (LVESV/LVEF) and clinical outcome was assessed using a combined endpoint of all-cause mortality and hospitalization because of heart failure.

Results: Median baseline estimated glomerular filtration rate was 62.8 (43.6-77.8) mL/min/1.73 m. Of the patients, 33.6% were in CKD stage 3, 11.0% in stage 4 and 1.1% in stage 5. LVEF and LVESV improved across all CKD stages; however, patients with CKD stages 1 and 2 exhibited a greater degree of improvement in LVEF (median 15% vs 10%, P < 0.001) and LVESV (median -37.2% vs -29.9%, P < 0.001) compared to patients with CKD stages 3-5. Despite a greater degree of reverse remodeling in CKD stages 1 and 2, the most accurate cut-off of remodeling predicting good clinical outcome was lower for patients with CKD stage 3-5, respectively: 5.5% vs 9.5% (LVEF) and -6.67% vs -12.41% (LVESV).

Conclusions: CRT results in reverse remodeling across all stages of CKD, although to a lesser extent in patients with renal dysfunction (CKD stage 3-5). However, patients with CKD derive benefit on outcome at a lesser degree of remodeling.
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http://dx.doi.org/10.1016/j.cardfail.2019.07.005DOI Listing
October 2019

The importance of dose optimisation in the treatment of iron deficiency in heart failure.

Acta Cardiol 2020 Oct 11;75(6):520-524. Epub 2019 Jun 11.

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

Treatment with ferric carboxymaltose (FCM) is limited to 1 g during one administration, which is insufficient in patients with a higher body weight or low haemoglobin (Hb). As a consequence, under-dosing might be common in clinical practice, yet the consequences remain unstudied. We retrospectively assessed all HFrEF-patients with iron-deficiency (ferritin <100 µg/l or between 100 and 300 µg/l if TSAT < 20%) receiving treatment with FCM between 2015 and 2017. This time-frame was chosen as during this we used a 1-g FCM-regimen for all patients (unless Hb = 14-15 mg/dl, than 500 mg). We compared the actual given dose versus the calculated target dose (according to the SmPC, with the difference between both being the dose deficit). We assessed the impact of dose deficits on clinical and biochemical status after 12 weeks. A total of 211 HFrEF patients were analysed. The actual given dose FCM was 918 ± 188 mg, while the calculated target dose was 1308 ± 470 mg. In 121(61%) patients, a standard dose of 1-g FCM resulted in a dose deficit, of whom 93 had a dose deficit of 500 mg and 35 had a dose deficit of 1000 mg. Follow-up was available in 81% of patients (median = 12 weeks). A dose deficit of 500 mg was associated with a 4.93 higher odds, while a dose deficit of 1000 mg was associated with a 7.78 higher odds of residual iron deficiency. After adjusting for baseline NYHA-class, a dose deficit was associated with less symptomatic improvement. During 442 ± 292 days of follow-up, 68 patients were readmitted with heart failure and 15 patients died. In an univariate model (but not in a multivariate model), a dose deficit was associated with adverse clinical outcome. A majority of HFrEF patients with iron deficiency require doses exceeding 1 g of FCM, and thus require follow-up appointments to correct a residual dose deficit. A residual dose deficit is associated with less functional and biochemical improvement.
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http://dx.doi.org/10.1080/00015385.2019.1625554DOI Listing
October 2020

Acetazolamide to increase natriuresis in congestive heart failure at high risk for diuretic resistance.

Eur J Heart Fail 2019 11 9;21(11):1415-1422. Epub 2019 May 9.

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

Aims: To investigate the effects of acetazolamide on natriuresis, decongestion, kidney function and neurohumoral activation in acute heart failure (AHF).

Methods And Results: This prospective, two-centre study included 34 AHF patients on loop diuretics with volume overload. All had a serum sodium concentration < 135 mmol/L and/or serum urea/creatinine ratio > 50 and/or an admission serum creatinine increase of > 0.3 mg/dL compared to baseline. Patients were randomised towards acetazolamide 250-500 mg daily plus bumetanide 1-2 mg bid vs. high-dose loop diuretics (bumetanide bid with daily dose twice the oral maintenance dose). The primary endpoint was natriuresis after 24 h. Natriuresis after 24 h was similar in the combinational treatment vs. loop diuretic only arm (264 ± 126 vs. 234 ± 133 mmol; P = 0.515). Loop diuretic efficiency, defined as natriuresis corrected for loop diuretic dose, was higher in the group receiving acetazolamide (84 ± 46 vs. 52 ± 42 mmol/mg bumetanide; P = 0.048). More patients in the combinational treatment arm had an increase in serum creatinine levels > 0.3 mg/dL (P = 0.046). N-terminal pro-B-type natriuretic peptide reduction and peak neurohumoral activation within 72 h were comparable among treatment arms. There was a non-significant trend towards lower all-cause mortality or heart failure readmissions in the group receiving acetazolamide with low-dose loop diuretics vs. high-dose loop diuretic monotherapy (P = 0.098).

Conclusion: Addition of acetazolamide increases the natriuretic response to loop diuretics compared to an increase in loop diuretic dose in AHF at high risk for diuretic resistance.

Trial Registration: ClinicalTrials.gov NCT01973335.
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http://dx.doi.org/10.1002/ejhf.1478DOI Listing
November 2019