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  1. AU=Kalra Paul R
  2. AU="Miller, Mona"
  3. AU="Tao Ming Sim"
  4. AU="Simen, Susanne"
  5. AU="Jole Costanza"
  6. AU="Paula, Camila S Y"
  7. AU="Azevedo, Helena S"
  8. AU=Molyneaux Phillip L.
  9. AU=Shimizu Kazuki
  10. AU=Pell Robert AU=Pell Robert
  11. AU="Aguiar, Liza"
  12. AU="Bahls, Christine"
  13. AU="Dongho Lee"
  14. AU=Houser Steven R.
  15. AU="Morgom M.M."
  16. AU="Jordana-Comajuncosa, Rosa"
  17. AU="Kaushansky, Alexis"
  18. AU="Bhatjiwale, Mohinish"
  19. AU="Velu, Chinavenmeni S"
  20. AU=Trayanova Natalia A
  21. AU=Jimeno-Gonzlez Silvia
  22. AU=Bussolino F
  23. AU="Almulla, Hanan"
  24. AU="Chen, Wenmei"
  25. AU=Zeng Weiqing

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  1. Artikel ; Online: Unanswered questions from the IRONMAN trial - Authors' reply.

    Ford, Ian / Kalra, Paul R

    Lancet (London, England)

    2023  Band 401, Heft 10387, Seite(n) 1495–1496

    Mesh-Begriff(e) Humans ; Swimming ; Running
    Sprache Englisch
    Erscheinungsdatum 2023-05-05
    Erscheinungsland England
    Dokumenttyp Letter ; Comment
    ZDB-ID 3306-6
    ISSN 1474-547X ; 0023-7507 ; 0140-6736
    ISSN (online) 1474-547X
    ISSN 0023-7507 ; 0140-6736
    DOI 10.1016/S0140-6736(23)00448-8
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  2. Artikel ; Online: A Systematic Review, Meta-Analysis, and Indirect Comparison of Blindly Adjudicated Cardiovascular Event Incidence with Ferric Derisomaltose, Ferric Carboxymaltose, and Iron Sucrose.

    Pollock, Richard F / Kalra, Philip A / Kalra, Paul R / Ahmed, Fozia Z

    Advances in therapy

    2022  Band 39, Heft 10, Seite(n) 4678–4691

    Abstract: Introduction: Intravenous (IV) iron is the preferred treatment for patients with iron deficiency anemia (IDA) who require rapid replenishment of iron stores or in whom oral iron is not tolerated or effective. Data from two large-scale randomized ... ...

    Abstract Introduction: Intravenous (IV) iron is the preferred treatment for patients with iron deficiency anemia (IDA) who require rapid replenishment of iron stores or in whom oral iron is not tolerated or effective. Data from two large-scale randomized controlled trials (RCTs) have recently been published reporting the incidence of adjudicated cardiovascular events after ferric derisomaltose (FDI) and iron sucrose (IS). The objective was to calculate the relative incidence of cardiovascular events with FDI and IS, and to conduct an indirect comparison with ferric carboxymaltose (FCM) based on previously published studies of cardiovascular risk.
    Methods: RCTs reporting the incidence of blindly adjudicated cardiovascular events in IDA patients treated with IV iron were identified by systematic literature review (SLR). Pairwise random effects meta-analyses of FDI versus IS, and FCM versus IS were conducted for the pre-specified adjudicated composite cardiovascular endpoint of: death due to any cause, nonfatal myocardial infarction, nonfatal stroke, unstable angina requiring hospitalization, congestive heart failure, arrhythmia, and protocol-defined hypertensive and hypotensive events. Analyses were also conducted for the composite endpoint excluding blood pressure events. Meta-analysis results were combined in an adjusted indirect comparison to provide an indirect estimate of cardiovascular risk with FDI versus FCM.
    Results: The SLR retrieved 694 unique articles, of which four were RCTs reporting the incidence of the composite cardiovascular endpoint; two studies comparing FCM (N = 1529) with IS (N = 1505), and two studies comparing FDI (N = 2008) with IS (N = 1000). The odds ratios of the composite CV endpoint were 0.59 (95% confidence interval: 0.39-0.90) for FDI versus IS, 1.12 (95% CI 0.90-1.40) for FCM versus IS, and the indirect OR for FDI versus FCM was 0.53 (95% CI 0.33-0.85).
    Conclusions: Pooling data from four large-scale RCTs suggested that FDI was associated with significantly lower incidence of cardiovascular adverse events compared to both FCM and IS.
    Mesh-Begriff(e) Anemia, Iron-Deficiency/drug therapy ; Cardiovascular Diseases/epidemiology ; Disaccharides ; Ferric Compounds/adverse effects ; Ferric Oxide, Saccharated/adverse effects ; Heart Failure ; Humans ; Incidence ; Iron ; Maltose/analogs & derivatives ; Randomized Controlled Trials as Topic
    Chemische Substanzen Disaccharides ; Ferric Compounds ; ferric carboxymaltose (6897GXD6OE) ; Maltose (69-79-4) ; ferric derisomaltose (AHU547PI9H) ; Iron (E1UOL152H7) ; Ferric Oxide, Saccharated (FZ7NYF5N8L)
    Sprache Englisch
    Erscheinungsdatum 2022-08-10
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Meta-Analysis ; Systematic Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 632651-1
    ISSN 1865-8652 ; 0741-238X
    ISSN (online) 1865-8652
    ISSN 0741-238X
    DOI 10.1007/s12325-022-02242-x
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  3. Artikel ; Online: Redefining Iron Deficiency in Patients With Chronic Heart Failure.

    Packer, Milton / Anker, Stefan D / Butler, Javed / Cleland, John G F / Kalra, Paul R / Mentz, Robert J / Ponikowski, Piotr / Talha, Khawaja M

    Circulation

    2024  

    Sprache Englisch
    Erscheinungsdatum 2024-05-11
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Review
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.124.068883
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  4. Artikel ; Online: Identification of three mechanistic pathways for iron-deficient heart failure.

    Packer, Milton / Anker, Stefan D / Butler, Javed / Cleland, John G F / Kalra, Paul R / Mentz, Robert J / Ponikowski, Piotr

    European heart journal

    2024  

    Abstract: Current understanding of iron-deficient heart failure is based on blood tests that are thought to reflect systemic iron stores, but the available evidence suggests greater complexity. The entry and egress of circulating iron is controlled by ... ...

    Abstract Current understanding of iron-deficient heart failure is based on blood tests that are thought to reflect systemic iron stores, but the available evidence suggests greater complexity. The entry and egress of circulating iron is controlled by erythroblasts, which (in severe iron deficiency) will sacrifice erythropoiesis to supply iron to other organs, e.g. the heart. Marked hypoferraemia (typically with anaemia) can drive the depletion of cardiomyocyte iron, impairing contractile performance and explaining why a transferrin saturation < ≈15%-16% predicts the ability of intravenous iron to reduce the risk of major heart failure events in long-term trials (Type 1 iron-deficient heart failure). However, heart failure may be accompanied by intracellular iron depletion within skeletal muscle and cardiomyocytes, which is disproportionate to the findings of systemic iron biomarkers. Inflammation- and deconditioning-mediated skeletal muscle dysfunction-a primary cause of dyspnoea and exercise intolerance in patients with heart failure-is accompanied by intracellular skeletal myocyte iron depletion, which can be exacerbated by even mild hypoferraemia, explaining why symptoms and functional capacity improve following intravenous iron, regardless of baseline haemoglobin or changes in haemoglobin (Type 2 iron-deficient heart failure). Additionally, patients with advanced heart failure show myocardial iron depletion due to both diminished entry into and enhanced egress of iron from the myocardium; the changes in iron proteins in the cardiomyocytes of these patients are opposite to those expected from systemic iron deficiency. Nevertheless, iron supplementation can prevent ventricular remodelling and cardiomyopathy produced by experimental injury in the absence of systemic iron deficiency (Type 3 iron-deficient heart failure). These observations, taken collectively, support the possibility of three different mechanistic pathways for the development of iron-deficient heart failure: one that is driven through systemic iron depletion and impaired erythropoiesis and two that are characterized by disproportionate depletion of intracellular iron in skeletal and cardiac muscle. These mechanisms are not mutually exclusive, and all pathways may be operative at the same time or may occur sequentially in the same patients.
    Sprache Englisch
    Erscheinungsdatum 2024-05-11
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 603098-1
    ISSN 1522-9645 ; 0195-668X
    ISSN (online) 1522-9645
    ISSN 0195-668X
    DOI 10.1093/eurheartj/ehae284
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  5. Artikel ; Online: Critical re-evaluation of the identification of iron deficiency states and effective iron repletion strategies in patients with chronic heart failure.

    Packer, Milton / Anker, Stefan D / Butler, Javed / Cleland, John G F / Kalra, Paul R / Mentz, Robert J / Ponikowski, Piotr / Talha, Khawaja M

    European journal of heart failure

    2024  

    Abstract: According to current guidelines, iron deficiency is defined by a serum ferritin level <100 ng/ml or a transferrin saturation (TSAT) <20% if the serum ferritin level is 100-299 μg/L. These criteria were developed to encourage the use of intravenous iron ... ...

    Abstract According to current guidelines, iron deficiency is defined by a serum ferritin level <100 ng/ml or a transferrin saturation (TSAT) <20% if the serum ferritin level is 100-299 μg/L. These criteria were developed to encourage the use of intravenous iron as an adjunct to erythropoiesis-stimulating agents in the treatment of renal anaemia. However, in patients with heart failure, these criteria are not supported by any pathophysiological or clinical evidence that they identify an absolute or functional iron deficiency state. A low baseline TSAT-but not serum ferritin level-appears to be a reliable indicator of the effect of intravenous iron to reduce major heart failure events. In randomized controlled trials, intravenous iron decreased the risk of cardiovascular death or total heart failure hospitalization in patients with a TSAT <20% (risk ratio 0.67 [0.49-0.92]) but not in patients with a TSAT ≥20% (risk ratio 0.99 [0.74-1.30]), with the magnitude of the risk reduction being proportional to the severity of hypoferraemia. Patients who were enrolled in clinical trials solely because they had a serum ferritin level <100 μg/L showed no significant benefit on heart failure outcomes, and it is noteworthy that serum ferritin levels of 20-300 μg/L lie entirely within the range of normal values for healthy adults. Current guidelines reflect the eligibility criteria of clinical trials, which inadvertently adopted unvalidated criteria to define iron deficiency. Reliance on these guidelines would lead to the treatment of many patients who are not iron deficient (serum ferritin level <100 μg/L but normal TSAT) and ignores the possibility of iron deficiency in patients with a low TSAT but with serum ferritin level of >300 μg/L. Importantly, analyses of benefit based on trial eligibility-driven guidelines substantially underestimate the magnitude of heart-failure-event risk reduction with intravenous iron in patients who are truly iron deficient. Based on all available data, we recommend a new mechanism-based and trial-tested approach that reflects the totality of evidence more faithfully than the historical process adopted by clinical investigators and by the guidelines. Until additional evidence is forthcoming, an iron deficiency state in patients with heart failure should be defined by a TSAT <20% (as long as the serum ferritin level is <400 μg/L), and furthermore, the use of a serum ferritin level <100 μg/L alone as a diagnostic criterion should be discarded.
    Sprache Englisch
    Erscheinungsdatum 2024-05-10
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review
    ZDB-ID 1483672-5
    ISSN 1879-0844 ; 1388-9842
    ISSN (online) 1879-0844
    ISSN 1388-9842
    DOI 10.1002/ejhf.3237
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  6. Artikel ; Online: Intravenous iron in patients with heart failure and iron deficiency: an updated meta-analysis.

    Graham, Fraser J / Pellicori, Pierpaolo / Kalra, Paul R / Ford, Ian / Bruzzese, Dario / Cleland, John G F

    European journal of heart failure

    2023  Band 25, Heft 4, Seite(n) 528–537

    Abstract: Aims: For patients with heart failure (HF) and iron deficiency (ID), randomized trials suggest that intravenous (IV) iron reduces hospitalizations for heart failure (HHF), but uncertainty exists about the effects in subgroups and the impact on mortality. ...

    Abstract Aims: For patients with heart failure (HF) and iron deficiency (ID), randomized trials suggest that intravenous (IV) iron reduces hospitalizations for heart failure (HHF), but uncertainty exists about the effects in subgroups and the impact on mortality. We conducted a meta-analysis of randomized trials investigating the effect of IV iron on clinical outcomes in patients with HF.
    Methods and results: We identified randomized trials published between 1 January 2000 and 5 November 2022 investigating the effect of IV iron versus standard care/placebo in patients with HF and ID in any clinical setting, regardless of HF phenotype. Trials of oral iron or not in English were not included. The main outcomes of interest were a composite of HHF and cardiovascular death (CVD), on HHF alone and on cardiovascular and all-cause mortality. Ten trials were identified with 3373 participants, of whom 1759 were assigned to IV iron. IV iron reduced the composite of recurrent HHF and CVD (rate ratio 0.75, 95% confidence interval [CI] 0.61-0.93; p < 0.01) and first HHF or CVD (odds ratio [OR] 0.72, 95% CI 0.53-0.99; p = 0.04). Effects on cardiovascular (OR 0.86, 95% CI 0.70-1.05; p = 0.14) and all-cause mortality (OR 0.93, 95% CI 0.78-1.12; p = 0.47) were inconclusive. Results were similar in analyses confined to the first year of follow-up, which was less disrupted by the COVID-19 pandemic. Subgroup analyses found little evidence of heterogeneity for the effect on the primary endpoint, although patients with transferrin saturation <20% (OR 0.67, 95% CI 0.49-0.92) may have benefited more than those with values ≥20% (OR 0.99, 95% CI 0.74-1.30) (heterogeneity p = 0.07).
    Conclusion: In patients with HF and ID, this meta-analysis suggests that IV iron reduces the risk of HHF but whether this is associated with a reduction in cardiovascular or all-cause mortality remains inconclusive.
    Mesh-Begriff(e) Humans ; Iron/therapeutic use ; Heart Failure/complications ; Heart Failure/drug therapy ; Pandemics ; COVID-19/complications ; Iron Deficiencies
    Chemische Substanzen Iron (E1UOL152H7)
    Sprache Englisch
    Erscheinungsdatum 2023-03-08
    Erscheinungsland England
    Dokumenttyp Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1483672-5
    ISSN 1879-0844 ; 1388-9842
    ISSN (online) 1879-0844
    ISSN 1388-9842
    DOI 10.1002/ejhf.2810
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  7. Artikel ; Online: Heart failure and acute renal dysfunction in the cardiorenal syndrome.

    Chahal, Rajinder S / Chukwu, Chukwuma A / Kalra, Paul R / Kalra, Philip A

    Clinical medicine (London, England)

    2020  Band 20, Heft 2, Seite(n) 146–150

    Abstract: Just under 1 million people in the UK have symptomatic heart failure. Decompensated heart failure is associated with a particularly poor prognosis with in-hospital mortality at around 10%. Over the last 30 years renin-angiotensin-aldosterone system ... ...

    Abstract Just under 1 million people in the UK have symptomatic heart failure. Decompensated heart failure is associated with a particularly poor prognosis with in-hospital mortality at around 10%. Over the last 30 years renin-angiotensin-aldosterone system antagonists have been shown to have incremental benefit on improved quality of life, reduced hospitalisation and mortality rates in those with heart failure with reduced ejection fraction. Concomitant chronic kidney disease and 'acute kidney injury' are common and associated with adverse outcomes.In patients with decompensated heart failure, congestion is a key driver of deterioration in renal function. Decongestion is fundamental to successful management. Yet it is not uncommon to see prognostically important medication (such as angiotensin converting enzyme inhibitors and mineralocorticoid antagonists) inappropriately stopped, along with under-diuresis of the patient. This leaves the patient still in a state of congestion without the prognostic medication at discharge, with resultant adverse outcome. The British Society for Heart Failure and the Renal Association have produced consensus guidance to help guide management in a more consistent fashion based on heart failure classification, whether the patient is congested and the degree of renal impairment. Early heart failure specialist review is associated with improved patient outcomes.
    Mesh-Begriff(e) Angiotensin-Converting Enzyme Inhibitors ; Cardio-Renal Syndrome/epidemiology ; Heart Failure/complications ; Heart Failure/epidemiology ; Humans ; Quality of Life ; Renin-Angiotensin System
    Chemische Substanzen Angiotensin-Converting Enzyme Inhibitors
    Sprache Englisch
    Erscheinungsdatum 2020-03-13
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2048646-7
    ISSN 1473-4893 ; 1470-2118
    ISSN (online) 1473-4893
    ISSN 1470-2118
    DOI 10.7861/clinmed.2019-0422
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  8. Artikel ; Online: Chronic kidney disease (CKD) and CKD-ism in heart failure - what a mess!

    Pellicori, Pierpaolo / Kalra, Paul R / Clark, Andrew L / Friday, Jocelyn M / Cleland, John G F

    European journal of heart failure

    2022  Band 24, Heft 11, Seite(n) 2196–2198

    Mesh-Begriff(e) Humans ; Heart Failure/complications ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/epidemiology
    Sprache Englisch
    Erscheinungsdatum 2022-10-12
    Erscheinungsland England
    Dokumenttyp Editorial
    ZDB-ID 1483672-5
    ISSN 1879-0844 ; 1388-9842
    ISSN (online) 1879-0844
    ISSN 1388-9842
    DOI 10.1002/ejhf.2696
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  9. Artikel: Iron Deficiency in Heart Failure: to Treat or Not to Treat?

    Pope, Michael / Kalra, Paul R

    Current treatment options in cardiovascular medicine

    2018  Band 20, Heft 8, Seite(n) 65

    Abstract: Purpose of review: This review will highlight the frequency and prognostic importance of iron deficiency in patients with chronic heart failure. An overview of the evidence surrounding the use of both oral and intravenous iron will be presented together ...

    Abstract Purpose of review: This review will highlight the frequency and prognostic importance of iron deficiency in patients with chronic heart failure. An overview of the evidence surrounding the use of both oral and intravenous iron will be presented together with discussion around what further data are required to establish what is the optimal long-term treatment strategy.
    Recent findings: Several recent randomised controlled studies have suggested that intravenous iron therapy in iron deficient patients with chronic heart failure and reduced ejection fraction can improve symptoms and quality of life, at least in the short term. There is no evidence of benefit from oral iron. Iron deficiency is common in patients with chronic heart failure and is associated with a worse prognosis. Whilst oral iron therapy has been shown to be of no benefit, randomised controlled trials suggest significant improvement in symptoms and quality of life with intravenous iron treatment over 6-12 months. Data are lacking on long-term efficacy, safety and impact on hard outcomes such as death and hospitalisation. Four large trials are currently recruiting patients and will provide definitive answers to these outstanding questions.
    Sprache Englisch
    Erscheinungsdatum 2018-07-18
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2057337-6
    ISSN 1534-3189 ; 1092-8464
    ISSN (online) 1534-3189
    ISSN 1092-8464
    DOI 10.1007/s11936-018-0661-8
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  10. Artikel ; Online: Qualitative interviews results from heart failure survey respondents on the interaction between symptoms and burden of self-care work.

    Austin, Rosalynn C / Schoonhoven, Lisette / Richardson, Alison / Kalra, Paul R / May, Carl R

    Journal of clinical nursing

    2022  Band 32, Heft 15-16, Seite(n) 4649–4662

    Abstract: Aims and objectives: Following a cross-sectional survey, a sub-sample of participants was interviewed to explore the interaction between symptoms and burden of treatment.: Background: Burden of treatment considers both the work associated with ... ...

    Abstract Aims and objectives: Following a cross-sectional survey, a sub-sample of participants was interviewed to explore the interaction between symptoms and burden of treatment.
    Background: Burden of treatment considers both the work associated with illness and treatment, including self-care work, as well as the individuals' capabilities and resources to engage in that work. The recent survey revealed the existence of a complex interaction.
    Design: Qualitative abductive analysis of semi-structured interviews.
    Methods: Adults with heart failure who participated in the survey were purposely sampled and invited to participate in semi-structured interviews. Location and mode of interview varied by participant choice. Excerpts from the verbatim transcripts were assessed for interactions between symptoms and burden of treatment, and when identified these were characterised and explained. We followed COREQ checklist for reporting. The patient research ambassador group was involved from research design to dissemination.
    Results: Participants (n = 32) consistently discussed how symptoms altered their capability to engage in self-care work. As symptom intensity increased the difficultly of their self-care work increased. A number of intervening factors appeared to influence the relationship between symptoms and burden of treatment. Intervening factors included illness pathology, illness identity, the value of the tasks attempted and available support structures. These factors may change how symptoms and burden of treatment are perceived; a model was constructed to explain and summarise these interactions.
    Conclusions: The interaction between symptoms and burden of treatment is complex. Intervening factors-illness identity and pathology, task value and performance, and available support structures-appear to exert a strong influence on the interaction between symptoms and burden of treatment.
    Relevance to clinical practice: These intervening factors present clinicians and researchers with opportunities to develop interventions that might reduce burden of treatment and improve symptoms and quality of life.
    Clinical trial registration: SYMPACT was registered with ISRCTN registry: ISRCTN11011943.
    Mesh-Begriff(e) Adult ; Humans ; Cross-Sectional Studies ; Heart Failure/therapy ; Quality of Life ; Self Care ; Surveys and Questionnaires
    Sprache Englisch
    Erscheinungsdatum 2022-08-09
    Erscheinungsland England
    Dokumenttyp Clinical Trial ; Journal Article
    ZDB-ID 1159483-4
    ISSN 1365-2702 ; 0962-1067 ; 1752-9816
    ISSN (online) 1365-2702
    ISSN 0962-1067 ; 1752-9816
    DOI 10.1111/jocn.16484
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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