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The wide overlap between the syndromes of chronic kidney disease (CKD) and chronic heart failure (HF) means that familiarity with the 2021 European Society of Cardiology guidelines is of importance to nephrologists. The common risk factors for the two syndromes together with the adverse cardiac structural remodelling associated with CKD means that many kidney disease patients experience breathlessness and fall within the HF phenotypes categorized in the guidelines. The management of HF is evolving rapidly leading to significant changes in the latest guideline iteration. The 2021 guidelines have changed from the 2016 version firstly by an increased focus on identifying the three phenotypes of HF to guide appropriate evidence-based management. Secondly, a new and simplified treatment algorithm for HF with reduced ejection fraction involving the rapid sequential initiation and up-titration of four 'pillars' of drug treatment-angiotensin-converting enzyme inhibitors or angiotensin-neprilysin inhibitors, beta blockers, mineralocorticoid receptor antagonists and now, thanks to convincing trial data, sodium-glucose co-transporter 2 inhibitors. Thirdly, guidelines for device therapy have been changed with down-graded advice on indications for primary prevention implantable cardioverter defibrillator therapy for patients with non-ischaemic HF and for cardiac resynchronization therapy with left bundle branch block (LBBB) and a QRS duration <150 ms. There are updated treatment plans for HF associated with non-cardiovascular comorbidities including CKD., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Objective: To improve the echocardiographic assessment of heart failure in patients with atrial fibrillation (AF) by comparing conventional averaging of consecutive beats with an index-beat approach, whereby measurements are taken after two cycles with similar R-R interval., Methods: Transthoracic echocardiography was performed using a standardised and blinded protocol in patients enrolled in the RATE-AF (RAte control Therapy Evaluation in permanent Atrial Fibrillation) randomised trial. We compared reproducibility of the index-beat and conventional consecutive-beat methods to calculate left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and E/e' (mitral E wave max/average diastolic tissue Doppler velocity), and assessed intraoperator/interoperator variability, time efficiency and validity against natriuretic peptides., Results: 160 patients were included, 46% of whom were women, with a median age of 75 years (IQR 69-82) and a median heart rate of 100 beats per minute (IQR 86-112). The index-beat had the lowest within-beat coefficient of variation for LVEF (32%, vs 51% for 5 consecutive beats and 53% for 10 consecutive beats), GLS (26%, vs 43% and 42%) and E/e' (25%, vs 41% and 41%). Intraoperator (n=50) and interoperator (n=18) reproducibility were both superior for index-beats and this method was quicker to perform (p<0.001): 35.4 s to measure E/e' (95% CI 33.1 to 37.8) compared with 44.7 s for 5-beat (95% CI 41.8 to 47.5) and 98.1 s for 10-beat (95% CI 91.7 to 104.4) analyses. Using a single index-beat did not compromise the association of LVEF, GLS or E/e' with natriuretic peptide levels., Conclusions: Compared with averaging of multiple beats in patients with AF, the index-beat approach improves reproducibility and saves time without a negative impact on validity, potentially improving the diagnosis and classification of heart failure in patients with AF., Competing Interests: Competing interests: KVB reports she was the research fellow for the RATE-AF trial funded by a National Institute for Health Research (NIHR) Career Development Fellowship awarded to DK. SG: none directly relevant to this work; funding through the BigData@Heart Innovative Medicines Initiative (grant no 116074). GL: none directly relevant to this work; consultant for Bayer/Janssen, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Novartis, Verseon and Daiichi Sankyo; and speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim and Daiichi Sankyo; no fees are directly received personally. PK reports grants from NIHR, European Union and British Heart Foundation, during the conduct of the study; grants and non-financial support from the European Union, British Heart Foundation, Leducq Foundation, Medical Research Council (UK) and German Centre for Heart Research, from several drug and device companies active in atrial fibrillation, and has received honoraria from several such companies, outside the submitted work; in addition, PK is listed as inventor on two patents held by the University of Birmingham (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783). JC: none directly relevant to this work; reports grants and personal fees from Bayer, Boehringer Ingelheim, Daiichi Sankyo and Pfizer/BMS; and personal fees from Medtronic, Boston Scientific and Abbott. KR reports grants from NIHR Oxford Biomedical Research Centre, University of Oxford; grants from UKRI’s Global Challenge Research Fund (ESRC), PEAK Urban Programme Grant Ref: ES/P011055/1; grants from the British Heart Foundation (grant numbers: FS/19/36/34346 and PG/18/65/33872); grants from Oxford Martin School, University of Oxford, during the conduct of the study; and personal fees from PLOS Medicine and from BMJ Heart, outside the submitted work. DK reports grants from the National Institute for Health Research (NIHR CDF-2015-08-074 and NIHR HTA-130280), the British Heart Foundation (PG/17/55/33087 and AA/18/2/34218), the European Society of Cardiology supported by educational grants from Boehringer Ingelheim/BMS-Pfizer Alliance/Bayer/Daiichi Sankyo/Boston Scientific, the NIHR/University of Oxford Biomedical Research Centre and British Heart Foundation/University of Birmingham Accelerator Award (STEEER-AF NCT04396418), EU/EFPIA Innovative Medicines Initiative (BigData@Heart 116074) and IRCCS San Raffaele/Menarini (Beta-blockers in Heart Failure Collaborative Group NCT0083244), in addition to personal fees from Bayer (Advisory Board), AtriCure (Speaker fees), Amomed (Advisory Board), Protherics Medicines Development (Advisory Board) and Myokardia (Advisory Board), all outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Cardiac parasympathetic control has prognostic significance in heart failure, but the control mechanisms of this system remain poorly defined. We have demonstrated previously a facilitatory role for nitric oxide (NO) in the parasympathetic control of heart rate in young healthy human subjects. In view of the complex abnormalities of regional NO activity observed in chronic heart failure, we now aim to establish if this mechanism is active in subjects with this condition. Groups of 12 heart failure patients [NYHA class II-III; mean age 52 years (range 38-67 years)] and 12 age/sex-matched healthy control subjects [mean age 50 years (range 36-62 years)] were studied. Heart rate variability and baroreflex sensitivity were measured during inhibition of endogenous NO production with N(G)-monomethyl-l-arginine (l-NMMA; 3 mg.h(-1).kg(-1)) and during administration of an equipressor dose of the control vasoconstrictor phenylephrine (12-36 microg.h(-1).kg(-1)). Basal levels of nitrate+nitrite were measured in the plasma as an indication of systemic NO production. In the heart failure patients, despite an equal rise in blood pressure with both drugs, high-frequency indices of heart rate variability increased less with l-NMMA than with phenylephrine: RMSSD (root mean square of successive RR-interval differences) increased by 4+/-2 compared with 26+/-8 ms (P<0.001) and high-frequency power increased by 97+/-62 compared with 1372+/-861 ms(2) (P<0.001). The increases in cross-spectral baroreflex sensitivity were also lower with l-NMMA than with phenylephrine [high-frequency alpha-index, 2.2+/-1.3 and 12.6+/-3.8 ms/mmHg respectively (P<0.001); low-frequency alpha-index, 1.3+/-0.9 and 4.3+/-1.7 ms/mmHg respectively (P<0.05)]. Healthy subjects showed a similar discrepancy in the response of high-frequency indices of heart rate variability to the two drugs, although baroreflex sensitivity responses were significantly different only for the high-frequency alpha-index. Levels of plasma nitrate+nitrite were significantly higher in the heart failure patients compared with controls. These data demonstrate that baroreflex-mediated cardiac parasympathetic activation in human heart failure, as in health, is dependent upon endogenous NO synthesis.

Aims: This study aimed to examine if the cardiac changes associated with uraemic cardiomyopathy are reversed by renal transplantation. Methods and results: MEDLINE, Embase, OpenGrey, and the Cochrane Library databases were searched from 1950 to March 2020. The primary outcome measure was left ventricular mass index. Secondary outcome measures included left ventricular dimensions and measures of diastolic and systolic function. Studies were included if they used any imaging modality both before and after successful renal transplantation. Data were analysed through meta‐analysis approaches. Weight of evidence was assessed through the Grading of Recommendations Assessment, Development and Evaluation system. Twenty‐three studies used echocardiography, and three used cardiac magnetic resonance imaging as their imaging modality. The methodological quality of the evidence was generally poor. Four studies followed up control groups, two using cardiac magnetic resonance imaging and two using echocardiography. Meta‐analysis of these studies indicated that there was no difference in left ventricular mass index between groups following transplantation {standardized mean difference −0.07 [95% confidence interval (CI) −0.41 to 0.26]; P = 0.67}. There was also no difference observed in left ventricular ejection fraction [mean difference 0.39% (95% CI −4.09% to 4.87%); P = 0.86] or left ventricular end‐diastolic volume [standardized mean difference −0.24 (95% CI −0.94 to 0.45); P = 0.49]. Inconsistent reporting of changes in diastolic dysfunction did not allow for any meaningful analysis or interpretation. Conclusions: The evidence does not support the notion that uraemic cardiomyopathy is reversible by renal transplantation. However, the evidence is limited by methodological weaknesses, which should be considered when interpreting these findings. [ABSTRACT FROM AUTHOR]

Importance: There is little evidence to support selection of heart rate control therapy in patients with permanent atrial fibrillation, in particular those with coexisting heart failure.Objective: To compare low-dose digoxin with bisoprolol (a β-blocker).Design, Setting, and Participants: Randomized, open-label, blinded end-point clinical trial including 160 patients aged 60 years or older with permanent atrial fibrillation (defined as no plan to restore sinus rhythm) and dyspnea classified as New York Heart Association class II or higher. Patients were recruited from 3 hospitals and primary care practices in England from 2016 through 2018; last follow-up occurred in October 2019.Interventions: Digoxin (n = 80; dose range, 62.5-250 μg/d; mean dose, 161 μg/d) or bisoprolol (n = 80; dose range, 1.25-15 mg/d; mean dose, 3.2 mg/d).Main Outcomes and Measures: The primary end point was patient-reported quality of life using the 36-Item Short Form Health Survey physical component summary score (SF-36 PCS) at 6 months (higher scores are better; range, 0-100), with a minimal clinically important difference of 0.5 SD. There were 17 secondary end points (including resting heart rate, modified European Heart Rhythm Association [EHRA] symptom classification, and N-terminal pro-brain natriuretic peptide [NT-proBNP] level) at 6 months, 20 end points at 12 months, and adverse event (AE) reporting.Results: Among 160 patients (mean age, 76 [SD, 8] years; 74 [46%] women; mean baseline heart rate, 100/min [SD, 18/min]), 145 (91%) completed the trial and 150 (94%) were included in the analysis for the primary outcome. There was no significant difference in the primary outcome of normalized SF-36 PCS at 6 months (mean, 31.9 [SD, 11.7] for digoxin vs 29.7 [11.4] for bisoprolol; adjusted mean difference, 1.4 [95% CI, -1.1 to 3.8]; P = .28). Of the 17 secondary outcomes at 6 months, there were no significant between-group differences for 16 outcomes, including resting heart rate (a mean of 76.9/min [SD, 12.1/min] with digoxin vs a mean of 74.8/min [SD, 11.6/min] with bisoprolol; difference, 1.5/min [95% CI, -2.0 to 5.1/min]; P = .40). The modified EHRA class was significantly different between groups at 6 months; 53% of patients in the digoxin group reported a 2-class improvement vs 9% of patients in the bisoprolol group (adjusted odds ratio, 10.3 [95% CI, 4.0 to 26.6]; P < .001). At 12 months, 8 of 20 outcomes were significantly different (all favoring digoxin), with a median NT-proBNP level of 960 pg/mL (interquartile range, 626 to 1531 pg/mL) in the digoxin group vs 1250 pg/mL (interquartile range, 847 to 1890 pg/mL) in the bisoprolol group (ratio of geometric means, 0.77 [95% CI, 0.64 to 0.92]; P = .005). Adverse events were less common with digoxin; 20 patients (25%) in the digoxin group had at least 1 AE vs 51 patients (64%) in the bisoprolol group (P < .001). There were 29 treatment-related AEs and 16 serious AEs in the digoxin group vs 142 and 37, respectively, in the bisoprolol group.Conclusions and Relevance: Among patients with permanent atrial fibrillation and symptoms of heart failure treated with low-dose digoxin or bisoprolol, there was no statistically significant difference in quality of life at 6 months. These findings support potentially basing decisions about treatment on other end points.Trial Registration: ClinicalTrials.gov Identifier: NCT02391337 and clinicaltrialsregister.eu Identifier: 2015-005043-13. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is associated with accelerated cardiovascular disease and heart failure. Endothelial nitric oxide synthase (eNOS) Glu298Asp single nucleotide polymorphism (SNP) genotype has been associated with a worse phenotype amongst patients with established heart failure and in patients with progression of their renal disease. The association of a cardiac functional difference in non-dialysis CKD patients with no known previous heart failure, and eNOS gene variant is investigated. Methods: 140 non-dialysis CKD patients, who had cardiac magnetic resonance (CMR) imaging and tissue doppler echocardiography as part of two clinical trials, were genotyped for eNOS Glu298Asp SNP retrospectively. Results: The median estimated glomerular filtration rate (eGFR) was 50mls/min and left ventricular ejection fraction (LVEF) was 74% with no overt diastolic dysfunction in this cohort. There were significant differences in LVEF across eNOS genotypes with GG genotype being associated with a worse LVEF compared to other genotypes (LVEF: GG 71%, TG 76%, TT 73%, p = 0.006). After multivariate analysis, (adjusting for age, eGFR, baseline mean arterial pressure, contemporary CMR heart rate, total cholesterol, high sensitive C-reactive protein, body mass index and gender) GG genotype was associated with a worse LVEF, and increased LV end-diastolic and systolic index (p = 0.004, 0.049 and 0.009 respectively). Conclusions: eNOS Glu298Asp rs1799983 polymorphism in CKD patients is associated with relevant sub-clinical cardiac remodelling as detected by CMR. This gene variant may therefore represent an important genetic biomarker, and possibly highlight pathways for intervention, in these patients who are at particular risk of worsening cardiac disease as their renal dysfunction progresses. [ABSTRACT FROM AUTHOR]

Background: Mitral regurgitation (MR) is common following myocardial infarction (MI). However, the subsequent trajectory of MR, and its impact on long-term outcomes are not well understood. This study aimed to examine the change in MR severity and associated clinical outcomes following MI. Methods: Records of patients admitted to a single centre between 2016 and 2017 with acute MI treated by percutaneous coronary intervention (PCI) were retrospectively examined. Results: 294/1000 consecutive patients had MR on baseline (pre-discharge) transthoracic echocardiography (TTE), of whom 126 (mean age: 70.9 ± 11.4 years) had at least one follow-up TTE. At baseline, most patients had mild MR (n = 94; 75%), with n = 30 (24%) moderate and n = 2 (2%) severe MR. Significant improvement in MR was observed at the first follow-up TTE (median 9 months from baseline; interquartile range: 3–23), with 36% having reduced severity, compared to 10% having increased MR severity (p < 0.001). Predictors of worsening MR included older age (mean: 75.2 vs. 66.7 years; p = 0.003) and lower creatinine clearance (mean: 60 vs. 81 mL/min, p = 0.015). Change in MR severity was significantly associated with prognosis: 16% with improving MR reached the composite endpoint of death or heart failure hospitalisation at 5 years, versus 44% (p = 0.004) with no change, and 59% (p < 0.001) with worsening MR. Conclusions: Of patients with follow-up TTE after MI, MR severity improved from baseline in approximately one-third, was stable in around half, with the remainder having worsening MR. Patients with persistent or worsening MR had worse clinical outcomes than those with improving MR. [ABSTRACT FROM AUTHOR]

Chronic kidney disease is associated with elevated cardiovascular risk, and heart failure and arrhythmias are the biggest causes of cardiovascular death in this population. Increased arterial stiffness is a hallmark of chronic kidney disease and is associated with adverse alterations in cardiac structure and function that may predispose to an increased risk of cardiovascular death. These changes are already apparent in early kidney disease, which is highly prevalent in the developed world. The mechanisms underlying increased arterial stiffness in chronic kidney disease are undoubtedly complex, but an understanding is paramount to enable the development of novel therapeutic strategies to prevent or reverse this pathophysiology and therefore reduce the cardiovascular disease burden in this high-risk cohort. [ABSTRACT FROM AUTHOR]

There is substantial animal data suggesting that nitric oxide (NO) has an important role as a modulator of cardiac autonomic control with a net vagotonic and sympatholytic role. Recent human work would support this concept. This study investigated the effects of the NO donor glyceryl trinitrate (GTN) upon measures of cardiac vagal activity in heart failure. Twelve stable chronic heart failure patients were studied in a randomised double blind, placebo controlled crossover study to assess the effects of chronic treatment with transdermal GTN (10 mg per day) on heart rate variability (HRV) measures of cardiac vagal activity. No significant difference between GTN and placebo was observed in mean arterial blood pressure and most measures of HRV and baroreflex sensitivity (BRS). BRS measured by the alpha-LF index showed a small rise. In conclusion, chronic GTN administration does not produce a significant increase in HRV measures of cardiac vagal activity in patients with heart failure. [ABSTRACT FROM AUTHOR]