Global lessons from deaths from heart failure in UK hospitals

The National Confidential Enquiry into Patient Outcome and Death (NCEPOD) has recently published a review of the care received by patients who died in UK hospitals following an admission with acute heart failure (HF).1 A sample of up to six adults who died during an admission to each hospital in the UK in 2016 was selected, with a total of 603 deaths being examined in detail by a multidisciplinary group of case reviewers. Various aspects of care, both organisational and clinical, were reviewed and graded as either good practice, room for improvement or less than satisfactory

Inter-study repeatability of circumferential strain and diastolic strain rate by CMR tagging, feature tracking and tissue tracking in ST-segment elevation myocardial infarction

Strain assessment allows accurate evaluation of myocardial function and mechanics in ST-segment elevation myocardial infarction (STEMI). Strain using cardiovascular magnetic resonance (CMR) has traditionally been assessed with tagging but limitations of this technique have led to more widespread use of alternative methods, which may be more robust. We compared the inter-study repeatability of circumferential global peak-systolic strain (Ecc) and peak-early diastolic strain rate (PEDSR) derived by tagging with values obtained using novel cine-based software: Feature Tracking (FT) (TomTec, Germany) and Tissue Tracking (TT) (Circle cvi42, Canada) in patients following STEMI. Twenty male patients (mean age 56 ± 10 years, mean infarct size 13.7 ± 7.1% of left ventricular mass) were randomised to undergo CMR 1–5 days post-STEMI at 1.5 T or 3.0 T, repeated after ten minutes at the same field strength. Ecc and PEDSR were assessed using tagging, FT and TT. Inter-study repeatability was evaluated using Bland–Altman analyses, coefficients of variation (CoV) and intra-class correlation coefficient (ICC). Ecc (%) was significantly lower with tagging than with FT or TT at 1.5 T (− 9.5 ± 3.3 vs. − 17.5 ± 3.8 vs. −15.5 ± 5.2, respectively, p < 0.001) and 3.0 T (− 13.1 ± 1.8 vs. − 19.4 ± 2.9 vs. − 17.3 ± 2.1, respectively, p = 0.001). This was similar for PEDSR (.s−1): 1.5 T (0.6 ± 0.2 vs. 1.5 ± 0.4 vs. 1.0 ± 0.4, for tagging, FT and TT respectively, p < 0.001) and 3.0 T (0.6 ± 0.2 vs. 1.5 ± 0.3 vs. 0.9 ± 0.3, respectively, p < 0.001). Inter-study repeatability for Ecc at 1.5 T was good for tagging and excellent for FT and TT: CoV 16.7%, 6.38%, and 8.65%, respectively. Repeatability for Ecc at 3.0 T was good for all three techniques: CoV 14.4%, 11.2%, and 13.0%, respectively. However, repeatability of PEDSR was generally lower than that for Ecc at 1.5 T (CoV 15.1%, 13.1%, and 34.0% for tagging, FT and TT, respectively) and 3.0 T (CoV 23.0%, 18.6%, and 26.2%, respectively). Following STEMI, Ecc and PEDSR are higher when measured with FT and TT than with tagging. Inter-study repeatability of Ecc is good for tagging, excellent for FT and TT at 1.5 T, and good for all three methods at 3.0 T. The repeatability of PEDSR is good to moderate at 1.5 T and moderate at 3.0 T. Cine-based methods to assess Ecc following STEMI may be preferable to tagging

A novel form of glycolytic metabolism‐dependent cardioprotection revealed by PKCα and β inhibition

Background Hyperglycaemia has a powerful association with adverse prognosis for patients with acute coronary syndromes (ACS). Previous work shows high glucose prevents ischaemic preconditioning and causes electrical and mechanical disruption via PKCα/β activation. The aims of this study were to: 1) determine whether the adverse clinical association of hyperglycaemia in ACS can be replicated in preclinical cellular models of ACS. 2) Ascertain the importance of PKCα/β activation to the deleterious effect of glucose. Methods Freshly isolated rat, guinea pig or rabbit cardiomyocytes were exposed to simulated ischaemia after incubation in the presence of normal (5 mm) or high (20 mm) glucose in the absence or presence of small molecule or tat‐peptide‐linked PKCαβ inhibitors. In each of the 4 conditions, the following hallmarks of cardioprotection were recorded using electrophysiology or fluorescent imaging: cardiomyocyte contraction & survival, action potential stability & time to failure, intracellular calcium & ATP, mitochondrial depolarisation, ischaemia‐sensitive leak current and time to Kir6.2 opening. Results High glucose alone resulted in decreased cardiomyocyte contraction and survival, however, imparted cardioprotection in the presence of PKCα/β inhibitors. This cardioprotective phenotype displayed improvements in all measured parameters and decreased myocardium damage during whole heart coronary ligation experiments. Conclusions High glucose is deleterious to cellular and whole‐heart models of simulated ischaemia, in keeping with the clinical association of hyperglycaemia with adverse outcome in ACS. PKCαβ inhibition revealed high glucose to show a cardioprotective phenotype in this setting. This study suggests the potential for therapeutic application of PKCαβ inhibition in ACS associated with hyperglycaemia

16-year trends in 30-day cause specific readmissions following hospitalisation for heart failure in england by sex, socioeconomic status and ethnicity.

Background: Reducing the high cost and burden of early readmissions after hospitalisation for HF has become a health policy priority of recent years, yet prior trend data are conflicting and UK data are scarce. This study investigates 16-year trends in 30-day cause-specific readmissions after hospitalisation for heart failure (HF), by gender, socioeconomic status and ethnicity. Methods: Using Hospital Episodes Statistics linked to socioeconomic and death data, we identified index admissions for HF in England (2002-2018). Trends in 30-day cause-specific readmissions by gender, socioeconomic status and ethnicity were estimated and patient characteristics of readmission were identified. Results: There were 698.983 index admissions for HF, median age 81 years [IQR 14], 50% male, 82% White, 3.1% South Asian, 1.7% Black, 16% most and 22% least affluent. In hospital deaths occurred in 108.798 patients (16%), but reduced from 20% to 12% over time (Figure 1a). A further 31.178 deaths (5%) occurred by 30 days. Between 2002-2006 and 2014-2018, age adjusted 30-day readmissions for any cause increased from 19% to 22%, an average increase of 1.4% (95% CI 1.3, 1.5) per annum. Readmissions for HF (6%) and ‘other CVD’ (3%) remained stable but readmissions for non-CVD causes increased from 10% to 13% at a rate of 2.6% (2.4, 2.7) per annum (Figure 1). Rates were similar by gender but there were diverging trends by ethnicity. Black groups experienced a 50% increase in readmissions for HF (6% to 9%, interaction-p 0.03) and South Asian groups had more rapidly increasing rates of readmissions for non-CVD causes (interaction-p 0.04). Non-CVD readmissions (12%) were also more prominent in the least (15%; 15, 15) compared to the most affluent group (12%; 12, 12) (see Table). Strongest predictors for HF readmission were Black ethnicity and CKD, whilst cardiac procedures and cardiologist care during the index admission were protective. For non-CVD readmissions, strongest predictors were non-CVD comorbidities (Cancer, COPD, CVA and depression), whilst cardiologist care was protective. Conclusions: In HF, despite readmission reduction policies, 30-day readmissions have been increasing. This change is driven by non-cardiovascular causes and impacts the least affluent and ethnic minority groups the most. Readmission reduction programmes require close consideration of patient factors and a multidisciplinary approach to specialist non-cardiovascular care. </p

Symptoms and signs in patients with heart failure: Association with 3-month hospitalisation and mortality

Objectives: To determine the association between symptoms and signs reported in primary care consultations following a new diagnosis of heart failure (HF), and 3-month hospitalisation and mortality. Design: Nested case-control study with density-based sampling. Setting: Clinical Practice Research Datalink, linked to hospitalisation and mortality (1998-2020). Participants: Database cohort of 86 882 patients with a new HF diagnosis. In two separate analyses for (1) first hospitalisation and (2) death, we compared the 3-month history of symptoms and signs in cases (patients with HF with the event), with their respective controls (patients with HF without the respective event, matched on diagnosis date (& plusmn;1 month) and follow-up time). Controls could be included more than once and later become a case. Main outcome measures: All-cause, HF and non-cardiovascular disease (non-CVD) hospitalisation and mortality. Results: During a median follow-up of 3.22 years (IQR: 0.59-8.18), 56 677 (65%) experienced first hospitalisation and 48 146 (55%) died. These cases were matched to 356 714 and 316 810 HF controls, respectively. For HF hospitalisation, the strongest adjusted associations were for symptoms and signs of fluid overload: pulmonary oedema (adjusted OR 3.08; 95% CI 2.52, 3.64), shortness of breath (2.94; 2.77, 3.11) and peripheral oedema (2.16; 2.00, 2.32). Generic symptoms also showed significant associations: depression (1.50; 1.18, 1.82), anxiety (1.35; 1.06, 1.64) and pain (1.19; 1.10, 1.28). Non-CVD hospitalisation had the strongest associations with chest pain (2.93; 2.77, 3.09), fatigue (1.87; 1.73, 2.01), general pain (1.87; 1.81, 1.93) and depression (1.59; 1.44, 1.74). Conclusions: In the primary care HF population, routinely recorded cardiac and non-specific symptoms showed differential risk associations with hospitalisation and mortality. & copy; Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ

Peritoneal Ultrafiltration for Heart Failure: Lessons from a Randomised Controlled Trial

Peritoneal ultrafiltration (PuF) has been employed for severe heart failure (HF), but evidence for its benefit is lacking. The Peritoneal Dialysis for Heart Failure (PDHF) study was a multicenter prospective randomized controlled trial which aimed to investigate this issue. The trial stopped early due to inadequate recruitment. We describe methods, trial activity, and lessons learned.The trial aimed to recruit 130 participants with severe diuretic-resistant HF (New York Heart Association [NYHA] 3/4) and chronic kidney disease (CKD) stage 3/4 on optimal medical treatment for ≥ 4 weeks from 6 UK centers. Participants were randomized to either continuation of conventional HF treatment or to additionally receiving PuF (1 overnight exchange using Icodextrin dialysate). Primary outcome was change in 6-minute walk test (6MWT) between baseline and 28 weeks (end of trial). Secondary outcomes were changes in patient reported quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire, short form 36 (SF 36) health survey results, hospitalization, and mortality.Over a 2-year period, 290 patients were screened from which only 20 met inclusion criteria and 10 were recruited. Reasons for ineligibility were fluctuating estimated glomerular filtration rate (eGFR), suboptimal HF treatment, frailty, and patients being too unwell for randomization. Barriers to recruitment included patient frailty, with some participants considered only when they were at end of life, unwillingness to engage in an invasive therapy, and suboptimal coordination between cardiology and renal services. This is a challenging patient group in which to perform research, and lessons learned from the peritoneal dialysis (PD)-HF trial will be helpful in the planning of future studies in this area.</p

Combined use of trimethylamine N-oxide with BNP for risk stratification in heart failure with preserved ejection fraction: findings from the DIAMONDHFpEF study

Circulating levels of Trimethylamine N-oxide (TMAO), a gut microbiome-mediated metabolite related to Western diet1, 2 , have been shown to be associated with risk stratification and outcome in patients with heart failure (HF) with reduced ejection fraction (HFrEF) 3-6 . The aim of the present study was to assess the associations between TMAO with outcomes in patients with HF with preserved ejection fraction (HFpEF)

Effects of Serelaxin in Patients with Acute Heart Failure

BACKGROUND Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. METHODS In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTS A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONS In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778. opens in new tab.

Differential left ventricular and left atrial remodelling in heart failure with preserved ejection fraction patients with and without diabetes

Background: Attempts to characterize cardiac structure in heart failure with preserved ejection fraction (HFpEF) in people with type 2 diabetes (T2D) have yielded inconsistent findings. We aimed to determine whether patients with HFpEF and T2D have a distinct pattern of cardiac remodelling compared with those without diabetes and whether remodelling was related to circulating markers of inflammation and fibrosis and clinical outcomes. Methods: We recruited 140 patients with HFpEF (75 with T2D and 65 without). Participants underwent comprehensive cardiovascular phenotyping, including echocardiography, cardiac magnetic resonance imaging and plasma biomarker profiling. Results: Patients with T2D were younger (age 70 ± 9 versus 75 ± 9y, p = 0.002), with evidence of more left ventricular (LV) concentric remodelling (LV mass/volume ratio 0.72 ± 0.15 versus 0.62 ± 0.16, p = 0.024) and smaller indexed left atrial (LA) volumes (maximal LA volume index 48 ± 20 versus 59 ± 29 ml/m2, p = 0.004) than those without diabetes. Plasma biomarkers of inflammation and extracellular matrix remodelling were elevated in those with T2D. Overall, there were 45 hospitalizations for HF and 22 deaths over a median follow-up period of 47 months [interquartile range (IQR) 38–54]. There was no difference in the primary composite endpoint of hospitalization for HF and mortality between groups. On multivariable Cox regression analysis, age, prior HF hospitalization, history of pulmonary disease and LV mass/volume were independent predictors of the primary endpoint. Conclusions: Patients with HFpEF and T2D have increased concentric LV remodelling, smaller LA volumes and evidence of increased systemic inflammation compared with those without diabetes. This suggests the underlying pathophysiology for the development of HFpEF is different in patients with and without T2D. ClinicalTrials.gov identifier: NCT03050593

Rationale and design of the United Kingdom Heart Failure with Preserved Ejection Fraction Registry

Objective: Heart failure with preserved ejection fraction (HFpEF) is a common heterogeneous syndrome that remains imprecisely defined and consequently has limited treatment options and poor outcomes. Methods: The UK Heart Failure with Preserved Ejection Fraction Registry (UK HFpEF) is a prospective data-enabled cohort and platform study. The study will develop a large, highly characterised cohort of patients with HFpEF. A biobank will be established. Deep clinical phenotyping, imaging, multiomics and centrally held national electronic health record data will be integrated at scale, in order to reclassify HFpEF into distinct subgroups, improve understanding of disease mechanisms and identify new biological pathways and molecular targets. Together, these will form the basis for developing diagnostics and targeted therapeutics specific to subgroups. It will be a platform for more effective and efficient trials, focusing on subgroups in whom targeted interventions are expected to be effective, with consent in place to facilitate rapid recruitment, and linkage for follow-up. Patients with a diagnosis of HFpEF made by a heart failure specialist, who have had natriuretic peptide levels measured and a left ventricular ejection fraction >40% are eligible. Patients with an ejection fraction between 40% and 49% will be limited to no more than 25% of the cohort. Conclusions: UK HFpEF will develop a rich, multimodal data resource to enable the identification of disease endotypes and develop more effective diagnostic strategies, precise risk stratification and targeted therapeutics. Trial registration number: NCT05441839.</p