Association Between Type 2 Diabetes and Changes in Myocardial Structure, Contractile Function, Energetics, and Blood Flow Before and After Aortic Valve Replacement in Patients With Severe Aortic Stenosis.

BACKGROUND: Type 2 diabetes (T2D) is associated with an increased risk of left ventricular dysfunction after aortic valve replacement (AVR) in patients with severe aortic stenosis (AS). Persistent impairments in myocardial energetics and myocardial blood flow (MBF) may underpin this observation. Using phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance, this study tested the hypothesis that patients with severe AS and T2D (AS-T2D) would have impaired myocardial energetics as reflected by the phosphocreatine to ATP ratio (PCr/ATP) and vasodilator stress MBF compared with patients with AS without T2D (AS-noT2D), and that these differences would persist after AVR. METHODS: Ninety-five patients with severe AS without coronary artery disease awaiting AVR (30 AS-T2D and 65 AS-noT2D) were recruited (mean, 71 years of age [95% CI, 69, 73]; 34 [37%] women). Thirty demographically matched healthy volunteers (HVs) and 30 patients with T2D without AS (T2D controls) were controls. One month before and 6 months after AVR, cardiac PCr/ATP, adenosine stress MBF, global longitudinal strain, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and 6-minute walk distance were assessed in patients with AS. T2D controls underwent identical assessments at baseline and 6-month follow-up. HVs were assessed once and did not undergo 6-minute walk testing. RESULTS: Compared with HVs, patients with AS (AS-T2D and AS-noT2D combined) showed impairment in PCr/ATP (mean [95% CI]; HVs, 2.15 [1.89, 2.34]; AS, 1.66 [1.56, 1.75]; P<0.0001) and vasodilator stress MBF (HVs, 2.11 mL min g [1.89, 2.34]; AS, 1.54 mL min g [1.41, 1.66]; P<0.0001) before AVR. Before AVR, within the AS group, patients with AS-T2D had worse PCr/ATP (AS-noT2D, 1.74 [1.62, 1.86]; AS-T2D, 1.44 [1.32, 1.56]; P=0.002) and vasodilator stress MBF (AS-noT2D, 1.67 mL min g [1.5, 1.84]; AS-T2D, 1.25 mL min g [1.22, 1.38]; P=0.001) compared with patients with AS-noT2D. Before AVR, patients with AS-T2D also had worse PCr/ATP (AS-T2D, 1.44 [1.30, 1.60]; T2D controls, 1.66 [1.56, 1.75]; P=0.04) and vasodilator stress MBF (AS-T2D, 1.25 mL min g [1.10, 1.41]; T2D controls, 1.54 mL min g [1.41, 1.66]; P=0.001) compared with T2D controls at baseline. After AVR, PCr/ATP normalized in patients with AS-noT2D, whereas patients with AS-T2D showed no improvements (AS-noT2D, 2.11 [1.79, 2.43]; AS-T2D, 1.30 [1.07, 1.53]; P=0.0006). Vasodilator stress MBF improved in both AS groups after AVR, but this remained lower in patients with AS-T2D (AS-noT2D, 1.80 mL min g [1.59, 2.0]; AS-T2D, 1.48 mL min g [1.29, 1.66]; P=0.03). There were no longer differences in PCr/ATP (AS-T2D, 1.44 [1.30, 1.60]; T2D controls, 1.51 [1.34, 1.53]; P=0.12) or vasodilator stress MBF (AS-T2D, 1.48 mL min g [1.29, 1.66]; T2D controls, 1.60 mL min g [1.34, 1.86]; P=0.82) between patients with AS-T2D after AVR and T2D controls at follow-up. Whereas global longitudinal strain, 6-minute walk distance, and NT-proBNP all improved after AVR in patients with AS-noT2D, no improvement in these assessments was observed in patients with AS-T2D. CONCLUSIONS: Among patients with severe AS, those with T2D demonstrate persistent abnormalities in myocardial PCr/ATP, vasodilator stress MBF, and cardiac contractile function after AVR; AVR effectively normalizes myocardial PCr/ATP, vasodilator stress MBF, and cardiac contractile function in patients without T2D.

Outcomes following cardiac resynchronisation therapy in older people.

INTRODUCTION: Older patients may be less likely to receive cardiac resynchronisation therapy (CRT) for the management of heart failure. We aimed to describe the differences in clinical response, complications, and subsequent outcomes following CRT implantation compared to younger patients. METHODS: We conducted a retrospective cohort study of unselected, consecutive patients implanted with CRT devices between March 2008 and July 2017. We recorded complications, symptomatic and echocardiographic response, hospitalisation for heart failure, and all-cause mortality comparing patients aged <70, 70-79 and ≥ 80 years. RESULTS: Five hundred and seventy-four patients (median age 76 years [interquartile range 68-81], 73.3% male) received CRT. At baseline, patients aged ≥80 years had worse symptoms, were more likely to have co-morbidities, and less likely to be receiving comprehensive medical therapy, although left ventricular function was similar. Older patients were less likely to receive CRT-defibrillators compared to CRT-pacemakers. Complications were infrequent and not more common in older patients. Age was not a predictor of symptomatic or echocardiographic response to CRT (67.2%, 71.2% and 62.6% responders in patients aged <70, 70-79 and ≥ 80 years, respectively; P = 0.43), and time to first heart failure hospitalisation was similar across age groups (P = 0.28). Ten-year survival was lower for older patients (49.9%, 23.9% and 6.8% in patients aged <70, 70-79 and ≥ 80 years, respectively; P < 0.001). CONCLUSIONS: The benefits of CRT on symptoms and left ventricular function were not different in older patients despite a greater burden of co-morbidities and less optimal medical therapy. These findings support the use of CRT in an ageing population.

'Acute Heart Failure': Should We Abandon the Term Altogether?

PURPOSE OF REVIEW: The distinction between 'acute' and 'chronic' heart failure persists. Our review aims to explore whether reclassifying heart failure decompensation more accurately as an event within the natural history of chronic heart failure has the potential to improve outcomes. RECENT FINDINGS: Although hospitalisation for worsening heart failure confers a poor prognosis, much of this reflects chronic disease severity. Most patients survive hospitalisation with most deaths occurring in the post-discharge 'vulnerable phase'. Current evidence supports four classes of medications proven to reduce cardiovascular mortality for those who have heart failure with a reduced ejection fraction, with recent trials suggesting worsening heart failure events are opportunities to optimise these therapies. Abandoning the term 'acute heart failure' has the potential to give greater priority to initiating proven pharmacological and device therapies during decompensation episodes, in order to improve outcomes for those who are at the greatest risk.

Suboptimal Dosing of ß-Blockers in Chronic Heart Failure: A Missed Opportunity?

BACKGROUND: The evidence base for the benefits of ß-blockers in heart failure with reduced ejection fraction (HFrEF) suggests that higher doses are associated with better outcomes. OBJECTIVES: The aim of this study was to report the proportion of patients receiving optimized doses of ß-blockers, outcomes, and factors associated with suboptimal dosing. METHODS: This was a prospective cohort study of 390 patients with HFrEF undergoing clinical and echocardiography assessment at baseline and at 1 year. RESULTS: Two hundred thirty-seven patients (61%) were receiving optimized doses (≥5-mg/d bisoprolol equivalent), 72 (18%) could not be up-titrated (because of heart rate < 60 beats/min or systolic blood pressure <100 mm Hg), and the remaining 81 (21%) should have been. Survival was similarly reduced in those who could not and should have been receiving 5 mg/d or greater, and patient factors did not explain the failure to attain optimized dosing. CONCLUSIONS: Many patients with HFrEF are not receiving optimal dosing of ß-blockers, and in around half, there was no clear contraindication in terms of heart rate or blood pressure.

Personalized Rate-Response Programming Improves Exercise Tolerance After 6 Months in People With Cardiac Implantable Electronic Devices and Heart Failure: A Phase II Study.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is characterized by blunting of the positive relationship between heart rate and left ventricular (LV) contractility known as the force-frequency relationship (FFR). We have previously described that tailoring the rate-response programming of cardiac implantable electronic devices in patients with HFrEF on the basis of individual noninvasive FFR data acutely improves exercise capacity. We aimed to examine whether using FFR data to tailor heart rate response in patients with HFrEF with cardiac implantable electronic devices favorably influences exercise capacity and LV function 6 months later. METHODS: We conducted a single-center, double-blind, randomized, parallel-group trial in patients with stable symptomatic HFrEF taking optimal guideline-directed medical therapy and with a cardiac implantable electronic device (cardiac resynchronization therapy or implantable cardioverter-defibrillator). Participants were randomized on a 1:1 basis between tailored rate-response programming on the basis of individual FFR data and conventional age-guided rate-response programming. The primary outcome measure was change in walk time on a treadmill walk test. Secondary outcomes included changes in LV systolic function, peak oxygen consumption, and quality of life. RESULTS: We randomized 83 patients with a mean±SD age 74.6±8.7 years and LV ejection fraction 35.2±10.5. Mean change in exercise time at 6 months was 75.4 (95% CI, 23.4 to 127.5) seconds for FFR-guided rate-adaptive pacing and 3.1 (95% CI, -44.1 to 50.3) seconds for conventional settings (analysis of covariance; P=0.044 between groups) despite lower peak mean±SD heart rates (98.6±19.4 versus 112.0±20.3 beats per minute). FFR-guided heart rate settings had no adverse effect on LV structure or function, whereas conventional settings were associated with a reduction in LV ejection fraction. CONCLUSIONS: In this phase II study, FFR-guided rate-response programming determined using a reproducible, noninvasive method appears to improve exercise time and limit changes to LV function in people with HFrEF and cardiac implantable electronic devices. Work is ongoing to confirm our findings in a multicenter setting and on longer-term clinical outcomes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02964650.

Impact of the COVID-19 pandemic on the management of chronic heart failure.

The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented challenge. Meeting this has resulted in changes to working practices and the impact on the management of patients with heart failure with reduced ejection fraction (HFrEF) is largely unknown. We performed a retrospective, observational study contrasting patients diagnosed with HFrEF attending specialist heart failure clinics at a UK hospital, whose subsequent period of optimisation of medical therapy was during the COVID-19 pandemic, with patients diagnosed the previous year. The primary outcome was the change in equivalent dosing of ramipril and bisoprolol at 6-months. Secondary outcomes were the number and type of follow-up consultations, hospitalisation for heart failure and all-cause mortality. In total, 60 patients were diagnosed with HFrEF between 1 December 2019 and 30 April 2020, compared to 54 during the same period of the previous year. The absolute number of consultations was higher (390 vs 270; p = 0.69), driven by increases in telephone consultations, with a reduction in appointments with hospital nurse specialists. After 6-months, we observed lower equivalent dosing of ramipril (3.1 ± 3.0 mg vs 4.4 ± 0.5 mg; p = 0.035) and similar dosing of bisoprolol (4.1 ± 0.5 mg vs 4.9 ± 0.5 mg; p = 0.27), which persisted for ramipril (mean difference 1.0 mg, 95% CI 0.018-2.09; p = 0.046) and bisoprolol (mean difference 0.52 mg, 95% CI -0.23-1.28; p = 0.17) after adjustment for baseline dosing. We observed no differences in the proportion of patients who died (5.0% vs 7.4%; p = 0.59) or were hospitalised with heart failure (13.3% vs 9.3%; p = 0.49). Our study suggests the transition to telephone appointments and re-deployment of heart failure nurse specialists was associated with less successful optimisation of medical therapy, especially renin-angiotensin inhibitors, compared with usual care.

Advanced care planning during the COVID-19 pandemic: ceiling of care decisions and their implications for observational data.

BACKGROUND: Observational studies investigating risk factors in coronavirus disease 2019 (COVID-19) have not considered the confounding effects of advanced care planning, such that a valid picture of risk for elderly, frail and multi-morbid patients is unknown. We aimed to report ceiling of care and cardiopulmonary resuscitation (CPR) decisions and their association with demographic and clinical characteristics as well as outcomes during the COVID-19 pandemic. METHODS: Retrospective, observational study conducted between 5th March and 7th May 2020 of all hospitalised patients with COVID-19. Ceiling of care and CPR decisions were documented using the Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) process. Unadjusted and multivariable regression analyses were used to determine factors associated with ceiling of care decisions and death during hospitalisation. RESULTS: A total of 485 patients were included, of whom 409 (84·3%) had a documented ceiling of care; level one for 208 (50·9%), level two for 75 (18·3%) and level three for 126 (30·8%). CPR decisions were documented for 451 (93·0%) of whom 336 (74·5%) were 'not for resuscitation'. Advanced age, frailty, White-European ethnicity, a diagnosis of any co-morbidity and receipt of cardiovascular medications were associated with ceiling of care decisions. In a multivariable model only advanced age (odds 0·89, 0·86-0·93 p < 0·001), frailty (odds 0·48, 0·38-0·60, p < 0·001) and the cumulative number of co-morbidities (odds 0·72, 0·52-1·0, p = 0·048) were independently associated. Death during hospitalisation was independently associated with age, frailty and requirement for level two or three care. CONCLUSION: Ceiling of care decisions were made for the majority of patients during the COVID-19 pandemic, broadly in line with known predictors of poor outcomes in COVID-19, but with a focus on co-morbidities suggesting ICU admission might not be a reliable end-point for observational studies where advanced care planning is routine.

Long-term Outcomes Are Poor in Intravenous Drug Users Following Infective Endocarditis, Even After Surgery.

BACKGROUND: Previous studies of outcomes in people who inject drugs (PWID) with infective endocarditis (IE) have often been retrospective, have had small sample sizes, and the duration of follow-up has been short and limited to patients who were operated on. METHODS: PWID treated for IE between 1 January 2006 and 31 December 2016 were identified from a prospectively collected database. PWID hospitalized with other infections acted as a novel comparison group. Outcomes were all-cause mortality, cause of death, relapse, recurrence, and reoperation. RESULTS: There were 105 episodes of IE in 92 PWID and 112 episodes of other infections in 107 PWID in whom IE was suspected but rejected. Survival at 30 days for the IE group was 85%, and 30-day survival following surgery was 96%. The most common pathogens were Staphylococcus species (60%) and Streptococcus species (30%). The surgical intervention rate was 47%. Survival for the IE group at 1, 3, 5, and 10 years was 74%, 63%, 58%, and 44%, respectively. This was significantly lower compared with the comparator group of other infections in PWID (P = .0002). Mortality was higher in patients who required surgery compared with those who did not (hazard ratio, 1.8 [95% confidence interval, .95-3.3]). The commonest cause of death was infection (66%), usually a further episode of IE (55%). CONCLUSIONS: Although early survival was good, long-term life expectancy was low. This was attributable to ongoing infection risk, rather than other factors known to affect prognosis in PWID. Surgery conferred no long-term survival advantage. More efforts are needed to reduce reinfection risk following an episode of IE in PWID.While early survival for people who inject drugs (PWID) with infective endocarditis is good, long-term survival is poor due to ongoing infection risk. Surgery conferred no long-term survival advantage, so more efforts are needed to reduce reinfection risks for PWID.

The Surprise Question and clinician-predicted prognosis: systematic review and meta-analysis.

BACKGROUND: The Surprise Question, 'Would you be surprised if this person died within the next year?' is a simple tool that can be used by clinicians to identify people within the last year of life. This review aimed to determine the accuracy of this assessment, across different healthcare settings, specialties, follow-up periods and respondents. METHODS: Searches were conducted of Medline, Embase, AMED, PubMed and the Cochrane Central Register of Controlled Trials, from inception until 01 January 2024. Studies were included if they reported original data on the ability of the Surprise Question to predict survival. For each study (including subgroups), sensitivity, specificity, positive and negative predictive values and accuracy were determined. RESULTS: Our dataset comprised 56 distinct cohorts, including 68 829 patients. In a pooled analysis, the sensitivity of the Surprise Question was 0.69 ((0.64 to 0.74) I2=97.2%), specificity 0.69 ((0.63 to 0.74) I2=99.7%), positive predictive value 0.40 ((0.35 to 0.45) I2=99.4%), negative predictive value 0.89 ((0.87 to 0.91) I2=99.7%) and accuracy 0.71 ((0.68 to 0.75) I2=99.3%). The prompt performed best in populations with high event rates, shorter timeframes and when posed to more experienced respondents. CONCLUSIONS: The Surprise Question demonstrated modest accuracy with considerable heterogeneity across the population to which it was applied and to whom it was posed. Prospective studies should test whether the prompt can facilitate timely access to palliative care services, as originally envisioned. PROSPERO REGISTRATION NUMBER: CRD32022298236.

Is conduction system pacing a panacea for pacemaker therapy?

INTRODUCTION: While supported by robust evidence and decades of clinical experience, right ventricular apical pacing for bradycardia is associated with a risk of progressive left ventricular dysfunction. Cardiac resynchronization therapy for heart failure with reduced ejection fraction can result in limited electrical resynchronization due to anatomical constraints and epicardial stimulation. In both settings, directly stimulating the conduction system below the atrio-ventricular node (either the bundle of His or the left bundle branch area) has potential to overcome these limitations. Conduction system pacing has met with considerable enthusiasm in view of the more physiological electrical conduction pattern, is rapidly becoming the preferred option of pacing for bradycardia, and is gaining momentum as an alternative to conventional biventricular pacing. AREAS COVERED: This article provides a review of the current efficacy and safety data for both people requiring treatment for bradycardia and the management of heart failure with conduction delay and discusses the possible future roles for conduction system pacing in routine clinical practice. EXPERT OPINION: Conduction system pacing might be the holy grail of pacemaker therapy without the disadvantages of current approaches. However, hypothesis and enthusiasm are no match for robust data, demonstrating at least equivalent efficacy and safety to standard approaches.

Diabetes mellitus does not alter mortality or hospitalisation risk in patients with newly diagnosed heart failure with preserved ejection fraction: Time to rethink pathophysiological models of disease progression.

INTRODUCTION: Type 2 diabetes is a common and adverse prognostic co-morbidity for patients with heart failure with reduced ejection fraction (HFrEF). The effect of diabetes on long-term outcomes for heart failure with preserved ejection fraction (HFpEF) is less established. METHODS: Prospective cohort study of patients referred to a regional HF clinic with newly diagnosed with HFrEF and HFpEF according to the 2016 European Society of Cardiology guidelines. The association between diabetes, all-cause mortality and hospitalisation was quantified using Kaplan-Meier or Cox regression analysis. RESULTS: Between 1st May 2012 and 1st May 2013, of 960 unselected consecutive patients referred with suspected HF, 464 and 314 patients met the criteria for HFpEF and HFrEF respectively. Within HFpEF and HFrEF groups, patients with diabetes were more frequently male and in both groups patients with diabetes were more likely to be treated with ß-adrenoceptor antagonists and angiotensin converting enzyme inhibitors. After adjustment for age, sex, medical therapy and co-morbidities, diabetes was associated with increased mortality in individuals with HFrEF (HR 1.46 95% CI: 1.05-2.02; p = .023), but not in those with HFpEF (HR 1.26 95% CI 0.92-1.72; p = .146). CONCLUSION: In unselected patients with newly diagnosed HF, diabetes is not an adverse prognostic marker in patients with HFpEF, but is in HFrEF.

Studying Adipose Endothelial Cell/Adipocyte Cross-Talk in Human Subcutaneous Adipose Tissue.

Microvascular endothelial cells (MVECs) have many critical roles, including control of vascular tone, regulation of thrombosis, and angiogenesis. Significant heterogeneity in endothelial cell (EC) genotype and phenotype depends on their vascular bed and host disease state. The ability to isolate MVECs from tissue-specific vascular beds and individual patient groups offers the opportunity to directly compare MVEC function in different disease states. Here, using subcutaneous adipose tissue (SAT) taken at the time of insertion of cardiac implantable electronic devices (CIED), we describe a method for the isolation of a pure population of functional human subcutaneous adipose tissue MVEC (hSATMVEC) and an experimental model of hSATMVEC-adipocyte cross-talk. hSATMVEC were isolated following enzymatic digestion of SAT by incubation with anti-CD31 antibody-coated magnetic beads and passage through magnetic columns. hSATMVEC were grown and passaged on gelatin-coated plates. Experiments used cells at passages 2-4. Cells maintained classic features of EC morphology until at least passage 5. Flow cytometric assessment showed 99.5% purity of isolated hSATMVEC, defined as CD31+/CD144+/CD45-. Isolated hSATMVEC from controls had a population doubling time of approximately 57 h, and active proliferation was confirmed using a cell proliferation imaging kit. Isolated hSATMVEC function was assessed using their response to insulin stimulation and angiogenic tube-forming potential. We then established an hSATMVEC-subcutaneous adipocyte co-culture model to study cellular cross-talk and demonstrated a downstream effect of hSATMVEC on adipocyte function. hSATMVEC can be isolated from SAT taken at the time of CIED insertion and are of sufficient purity to both experimentally phenotype and study hSATMVEC-adipocyte cross-talk.

Sodium-glucose cotransporter 2 inhibitors influence skeletal muscle pathology in patients with heart failure and reduced ejection fraction.

AIMS: Patients with heart failure and reduced ejection fraction (HFrEF) exhibit skeletal muscle pathology, which contributes to symptoms and decreased quality of life. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve clinical outcomes in HFrEF but their mechanism of action remains poorly understood. We aimed, therefore, to determine whether SGLT2i influence skeletal muscle pathology in patients with HFrEF. METHODS AND RESULTS: Muscle biopsies from 28 male patients with HFrEF (New York Heart association class I-III) treated with SGLT2i (>12 months) or without SGLT2i were compared. Comprehensive analyses of muscle structure (immunohistochemistry), transcriptome (RNA sequencing), and metabolome (liquid chromatography-mass spectrometry) were performed, and serum inflammatory profiling (ELISA). Experiments in mice (n = 16) treated with SGLT2i were also performed. Myofiber atrophy was ~20% less in patients taking SGLT2i (p = 0.07). Transcriptomics and follow-up measures identified a unique signature in patients taking SGLT2i related to beneficial effects on atrophy, metabolism, and inflammation. Metabolomics identified influenced tryptophan metabolism in patients taking SGLT2i: kynurenic acid was 24% higher and kynurenine was 32% lower (p < 0.001). Serum profiling identified that SGLT2i treatment was associated with lower (p < 0.05) pro-inflammatory cytokines by 26-64% alongside downstream muscle interleukin (IL)-6-JAK/STAT3 signalling (p = 008 and 0.09). Serum IL-6 and muscle kynurenine were correlated (R = 0.65; p < 0.05). Muscle pathology was lower in mice treated with SGLT2i indicative of a conserved mammalian response to treatment. CONCLUSIONS: Treatment with SGLT2i influenced skeletal muscle pathology in patients with HFrEF and was associated with anti-atrophic, anti-inflammatory, and pro-metabolic effects. These changes may be regulated via IL-6-kynurenine signalling. Together, clinical improvements following SGLT2i treatment in patients with HFrEF may be partly explained by their positive effects on skeletal muscle pathology.

Improving the management of left ventricular thrombus in a tertiary cardiology centre: a quality improvement project.

Left ventricular (LV) thrombus is an increasingly recognised complication following anterior myocardial infarction and non-ischaemic cardiomyopathy. Whilst vitamin K antagonists (VKA) remain the only approved therapeutic option to reduce the risk of systemic thromboembolism including stroke, the off-label use of direct oral anticoagulants (DOACs) is becoming an attractive alternative.We aimed to improve the diagnosis and management of LV thrombus at a tertiary cardiology centre using quality improvement methodology. Outcomes included increasing the use of DOACs from 25% to 70% over a period of 1 year and shorten length of time from diagnosis to repeat imaging to within 3-6 months as recommended by guidelines.During the first Plan-Do-Study-Action (PDSA) cycle, we identified 84 patients diagnosed with LV thrombus between 1 December 2012 and 30 June 2018. The majority (74%) were prescribed VKA. Repeat imaging occurred in 89% of patients, but only 55% using the same modality. The mean duration between diagnosis and repeat imaging was 233±251 days. There were no significant differences between VKA and DOAC in terms of thrombus resolution, systemic embolisation or clinically significant bleeding. We published trust-wide guidelines on the management of LV thrombus with recommendations supporting the use of DOACs and appropriate follow-up imaging. A second PDSA cycle undertaken between 1 October 2019 and 31 March 2020 identified a further 20 patients. DOAC use increased to 70% and 70% of patients underwent follow-up imaging following a mean duration of 140±61 days, although in only 36% using the same modality.Using quality improvement methodology, we confirmed safe and efficient use of DOAC in the setting of LV thrombus. We published trust guidelines supporting their use, which was associated with an increase in DOAC use and in earlier follow-up imaging in line with our recommendations.

Clinical implications and risk factors for QRS prolongation over time in heart failure patients.

BACKGROUND: QRS prolongation is an established prognostic marker in heart failure (HF). In contrast, the role of QRS width progression over time has been incompletely explored. The current study investigates the role of QRS width progression over time on clinical status and identifies underlying predictors. METHODS: Datasets of ≥ 2 consecutive visits from 100 attendees to our HF clinic between April and August 2021 were analysed for changes in QRS complex duration. RESULTS: In total 240 datasets were stratified into tertiles based on change in QRS duration (mm/month) (1st tertile: - 1.65 [1.50] 'regression'; 2nd tertile 0.03 [0.19] 'stable', 3rd tertile 3.57 [10.11] 'progression'). The incidence of the combined endpoint HF hospitalisation and worsening of symptomatic heart failure was significantly higher in the group with QRS width progression (3rd tertile) compared with the stable group (2nd tertile; log-rank test: p = 0.013). These patients were characterised by higher plasma NT-pro-BNP levels (p = 0.008) and higher heart rate (p = 0.007). A spline-based prediction model identified patients at risk of QRS width progression when NT-pro-BNP and heartrate were > 837 pg/ml and > 83/bpm, respectively. These markers were independent of guideline-directed medical HF therapy. Patients beyond both thresholds had a 14-fold increased risk of QRS width progression compared to those with neither or either alone (HR: 14.2 [95% 6.9 - 53.6]; p < 0.0001, p for interaction = 0.016). CONCLUSIONS: This pilot study demonstrates that QRS width progression is associated with clinical deterioration of HF. NTproBNP plasma levels and heart rate indicate patients at risk QRS width progression, independently of HF therapy.

Guideline-directed medical therapy is similarly effective in heart failure with mildly reduced ejection fraction.

AIMS: Current guidelines recommend that disease-modifying pharmacological therapies may be considered for patients who have heart failure with mildly reduced ejection fraction (HFmrEF). We aimed to describe the characteristics, outcomes, provision of pharmacological therapies and dose-related associations with mortality risk in HFmrEF. METHODS AND RESULTS: We explored data from two prospective observational studies, which permitted the examination of the effects of pharmacological therapies across a broad spectrum of left ventricular ejection fraction (LVEF). The combined dataset consisted of 2388 unique patients, with a mean age of 73.7 ± 13.2 years of whom 1525 (63.9%) were male. LVEF ranged from 5 to 71% (mean 37.2 ± 12.8%) and 1504 (63.0%) were categorised as having reduced ejection fraction (HFrEF), 421 (17.6%) as HFmrEF and 463 (19.4%) as preserved ejection fraction (HFpEF). Patients with HFmrEF more closely resembled HFrEF than HFpEF. Adjusted all-cause mortality risk was lower in HFmrEF (hazard ratio [HR] 0.86 (95% confidence interval [CI] 0.74-0.99); p = 0.040) and in HFpEF (HR 0.61 (95% CI 0.52-0.71); p < 0.001) compared to HFrEF. Adjusted all-cause mortality risk was lower in patients with HFrEF and HFmrEF who received the highest doses of beta-blockers or renin-angiotensin inhibitors. These associations were not evident in HFpEF. Once adjusted for relevant confounders, each mg equivalent of bisoprolol (HR 0.95 [95% CI 0.91-1.00]; p = 0.047) and ramipril (HR 0.95 [95%CI 0.90-1.00]; p = 0.044) was associated with incremental reductions in mortality risk in patients with HFmrEF. CONCLUSIONS: Pharmacological therapies were associated with lower mortality risk in HFmrEF, supporting guideline recommendations which extend the indications of these agents to all patients with LVEF < 50%. HFmrEF more closely resembles HFrEF in terms of clinical characteristics and outcomes. Pharmacological therapies are associated with lower mortality risk in HFmrEF and HFrEF, but not in HFpEF.