Association of Medication Intensity and Stages of Airflow Limitation With the Risk of Hospitalization or Death in Patients With Heart Failure and Chronic Obstructive Pulmonary Disease.

Importance: In heart failure (HF), chronic obstructive pulmonary disease (COPD) increases the risk of poor outcomes, but the effect of COPD severity is unknown. This information is important for early intervention tailored to the highest-risk groups. Objectives: To determine the associations between COPD medication intensity or stage of airflow limitation and the risk of hospitalization or death in patients with HF. Design, Setting, and Participants: This UK population-based, nested case-control study with risk-set sampling used the Clinical Practice Research Datalink linked to Hospital Episode Statistics between January 1, 2002, to January 1, 2014. Participants included patients aged 40 years and older with a new diagnosis of HF in their family practice clinical record. Data analysis was conducted from 2017 to 2018. Exposures: In patients with HF, those with COPD were compared with those without it. International COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD]) guidelines were used to stratify patients with COPD by 7 medication intensity levels and 4 airflow limitation severity stages using automatically recorded prescriptions and routinely requested forced expiratory volume in 1 second (FEV1) data. Main Outcomes and Measures: First all-cause admission or all-cause death. Results: There were 50 114 patients with new HF (median age, 79 years [interquartile range, 71-85 years]; 46% women) during the study period. In patients with HF, COPD (18 478 [13.8%]) was significantly associated with increased mortality (adjusted odds ratio [AOR], 1.31; 95% CI, 1.26-1.36) and hospitalization (AOR, 1.33; 95% CI, 1.26-1.39). The 3 most severe medication intensity levels showed significantly increasing mortality associations from full inhaler therapy (AOR, 1.17; 95% CI, 1.06-1.29) to oral corticosteroids (AOR, 1.69; 95% CI, 1.57-1.81) to oxygen therapy (AOR, 2.82; 95% CI, 2.42-3.28). The respective estimates for hospitalization were AORs of 1.17 (95% CI, 1.03-1.33), 1.75 (95% CI, 1.59-1.92), and 2.84 (95% CI, 1.22-3.63). Availability of spirometry data was limited but showed that increasing airflow limitation was associated with increased risk of mortality, with the following AORs: FEV1 80% or more, 1.63 (95% CI, 1.42-1.87); FEV1 50% to 79%, 1.69 (95% CI, 1.56-1.83); FEV1 30% to 49%, 2.21 (95% CI, 2.01-2.42); FEV1 less than 30%, 2.93 (95% CI, 2.49-3.43). The strength of associations between FEV1 and hospitalization risk were similar among stages ranging from FEV1 80% or more (AOR, 1.48; 95% CI, 1.31-1.68) to FEV1 less than 30% (AOR, 1.73; 95% CI, 1.40-2.12). Conclusions and Relevance: In the UK HF community setting, increasing COPD severity was associated with increasing risk of mortality and hospitalization. Prescribed COPD medication intensity and airflow limitation provide the basis for targeting high-risk groups

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)

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

Leg Ischaemia Management collaboration (LIMb): study protocol for a prospective cohort study at a single UK centre

Introduction Severe limb ischaemia (SLI) is the end-stage of peripheral arterial occlusive disease where the viability of the limb is threatened. Around 25% of patients with SLI will ultimately require a major lower limb amputation which has a substantial adverse impact on quality of life. A newly established rapid-access vascular limb salvage clinic and modern revascularisation techniques may reduce amputation rate. The aim of this study is to investigate the 12-month amputation rate in a contemporary cohort of patients and compare this to a historical cohort. Secondary aims are to investigate the use of frailty and cognitive assessments, and cardiac MRI in risk-stratifying patients with SLI undergoing intervention and establish a biobank for future biomarker analyses. Methods & analysis This single-centre prospective cohort study will recruit patients aged 18-110 years presenting with SLI. Those undergoing intervention will be eligible to undergo additional venepuncture (for biomarker analysis) and/or cardiac MRI. Those aged ≥65 years and undergoing intervention will also be eligible to undergo additional frailty and cognitive assessments. Follow-up will be at 12 and 24 months and subsequently via data-linkage with NHS digital to 10 years post-recruitment. Those undergoing cardiac MRI and/or frailty assessments will receive additional follow-up during the first 12 months to investigate for peri-operative myocardial infarction and frailty related outcomes, respectively. A sample size of 420 patients will be required to detect a 10% reduction in amputation rate in comparison to a similar sized historical cohort, with 90% power and 5% type-I error rate. Statistical analysis of this comparison will be by adjusted and unadjusted logistic regression analyses. Ethics & dissemination Ethical approval for this study has been granted by the UK National Research Ethics Service (19/LO/0132). Results will be disseminated to participants, via scientific meetings, peerreviewed medical journals and social media. Study registration ClinicalTrials.gov [NCT04027244

Proenkephalin and prognosis in heart failure with preserved ejection fraction: a GREAT network study.

BACKGROUND: Proenkephalin (PENK), a stable endogenous opioid biomarker related to renal function, has prognostic utility in acute and chronic heart failure. We investigated the prognostic utility of PENK in heart failure with preserved ejection fraction (HFpEF), and its relationship to renal function, Body Mass Index (BMI), and imaging measures of diastolic dysfunction. METHODS: In this multicentre study, PENK was measured in 522 HFpEF patients (ejection fraction > 50%, 253 male, mean age 76.13 ± 10.73 years) and compared to 47 age and sex-matched controls. The primary endpoint was 2-years composite of all-cause mortality and/or heart failure rehospitalisation (HF). A subset (n = 163) received detailed imaging studies. RESULTS: PENK levels were raised in HFpEF (median [interquartile range] 88.9 [62.1-132.0]) compared to normal controls (56.3 [47.9-70.5]). PENK was correlated to urea, eGFR, Body Mass Index and E/e' (rs 0.635, - 0.741, - 0.275, 0.476, respectively, p < 0.0005). During 2 years follow-up 144 patients died and 220 had death/HF endpoints. Multivariable Cox regression models showed PENK independently predicted 2 year death/HF [hazard ratio (for 1 SD increment of log-transformed biomarker) HR 1.45 [95% CI 1.12-1.88, p = 0.005]], even after adjustment for troponin (HR 1.59 [1.14-2.20, p = 0.006]), and Body Mass Index (HR 1.63 [1.13-2.33, p = 0.009]). PENK showed no interaction with ejection fraction status for prediction of poor outcomes. Net reclassification analyses showed PENK significantly improved classification of death/HF outcomes for multivariable models containing natriuretic peptide, troponin and Body Mass Index (p < 0.05 for all). CONCLUSIONS: In HFpEF, PENK levels are related to BMI, and measures of diastolic dysfunction and are prognostic for all-cause mortality and heart failure rehospitalisation