A global perspective of racial differences and outcomes in patients presenting with acute heart failure.

Important racial differences in characteristics, treatment, and outcomes of patients with acute heart failure (AHF) have been described. The objective of this analysis of the International Registry to assess medical Practice with longitudinal observation for Treatment of Heart Failure (REPORT-HF) registry was to investigate racial differences in patients with AHF according to country income level.

Left atrial structure and function in heart failure with reduced (HFrEF) versus preserved ejection fraction (HFpEF): systematic review and meta-analysis.

Left atrial (LA) structure and function in heart failure with reduced (HFrEF) versus preserved ejection fraction (HFpEF) is only established in small studies. Therefore, we conducted a systematic review of LA structure and function in order to find differences between patients with HFrEF and HFpEF. English literature on LA structure and function using echocardiography was reviewed to calculate pooled prevalence and weighted mean differences (WMD). A total of 61 studies, comprising 8806 patients with HFrEF and 9928 patients with HFpEF, were included. The pooled prevalence of atrial fibrillation (AF) was 34.4% versus 42.8% in the acute inpatient setting, and 20.1% versus 33.1% in the chronic outpatient setting when comparing between HFrEF and HFpEF. LA volume index (LAVi), LA reservoir global longitudinal strain (LAGLSR), and E/e' was 59.7 versus 52.7 ml/m2, 9.0% versus 18.9%, and 18.5 versus 14.0 in the acute inpatient setting, and 48.3 versus 38.2 ml/m2, 12.8% versus 23.4%, and 16.9 versus 13.5 in the chronic outpatient setting when comparing HFrEF versus HFpEF, respectively. The relationship between LAVi and LAGLSR was significant in HFpEF, but not in HFrEF. Also, in those studies that directly compared patients with HFrEF versus HFpEF, those with HFrEF had worse LAGLSR [WMD = 16.3% (22.05,8.61); p < 0.001], and higher E/e' [WMD = -0.40 (-0.56, -0.24); p < 0.05], while LAVi was comparable. When focusing on acute hospitalized patients, E/e' was comparable between patients with HFrEF and HFpEF. Despite the higher burden of AF in HFpEF, patients with HFrEF had worse LA global function. Left atrial myopathy is not specifically related to HFpEF.

Differences in Presentation, Management and Outcomes in Women and Men Presenting to an Emergency Department With Possible Cardiac Chest Pain.

BACKGROUND: Research suggests that female patients with acute coronary syndrome (ACS) experience delays in emergency department (ED) management and are less likely to receive guideline-based treatments and referrals for follow-up testing. Women are often found to have poorer clinical outcomes in comparison to men. This study aimed to assess current sex differences in the presentation, management and outcomes of patients with undifferentiated chest pain presenting to a tertiary ED. METHODS: Data were analysed from two prospective studies conducted at a single Australian site between 2007 and 2014. Eligible patients were those of 18 years of age or older presenting with at least 5 minutes of chest pain or other symptoms for which the treating physician planned to investigate for possible ACS. Presenting symptoms, ED time measures, follow-up testing and outcomes, including 30-day ACS and mortality, were measured and compared between male and female patients. RESULTS: Of 2349 (60% men) patients presenting with chest pain, 153 men and 51 women were diagnosed with ACS within 30days . Presenting symptoms were similar in men and women with confirmed ACS. Time from symptom onset to ED presentation, time spent in the ED and total time in hospital were similar between the sexes. Male and female patients had similar rates of follow-up provocative testing. After adjustment for clinical factors, the odds of undergoing angiography were 1.8 (95% CI: 1.36-2.40) times higher for men than women. Of those undergoing coronary angiography within 30 days, a smaller proportion of women, compared to men, received revascularisation. Within 30 days, three (0.2%) male and one (0.1%) female patient died. CONCLUSION: Minimal sex differences were observed in the contemporary emergency management of patients presenting with suspected ACS. Thirty-day outcomes were similarly low in men and women despite lower rates of coronary angiography and revascularisation in women. Further research is required to replicate these results in different hospital systems and cultural settings.

Artificial intelligence innovation in healthcare: Relevance of reporting guidelines for clinical translation from bench to bedside.

Artificial intelligence (AI) and digital innovation are transforming healthcare. Technologies such as machine learning in image analysis, natural language processing in medical chatbots and electronic medical record extraction have the potential to improve screening, diagnostics and prognostication, leading to precision medicine and preventive health. However, it is crucial to ensure that AI research is conducted with scientific rigour to facilitate clinical implementation. Therefore, reporting guidelines have been developed to standardise and streamline the development and validation of AI technologies in health. This commentary proposes a structured approach to utilise these reporting guidelines for the translation of promising AI techniques from research and development into clinical translation, and eventual widespread implementation from bench to bedside.

Epidemiology and Clinical Features of Heart Failure with Preserved Ejection Fraction.

Heart failure (HF) with preserved ejection (HFpEF) constitutes a large and growing proportion of patients with HF around the world, and is now responsible for more than half of all HF cases in ageing societies. While classically described as a condition of elderly, hypertensive women, recent studies suggest heterogeneity in clinical phenotypes involving differential characteristics and pathophysiological mechanisms. Despite a paucity of disease-modifying therapy for HFpEF, an understanding of phenotypic similarities and differences among patients with HFpEF around the world provides the foundation to recognise the clinical condition for early treatment, as well as to identify modifiable risk factors for preventive intervention. This review summarises the epidemiology of HFpEF, its common clinical features and risk factors, as well as differences by age, comorbidities, race/ethnicity and geography.

Subclinical vasculopathy and skeletal muscle metrics in the singapore longitudinal ageing study.

Frailty is associated with future cardiovascular events in older adults. This cross-sectional study examined the relationship between subclinical vasculopathy with measures of skeletal muscle mass and function. Asymptomatic community-dwelling Asians ≥55 years underwent assessments for subclinical vasculopathy (carotid intima-media thickness (cIMT), aortic and carotid stiffness, and endothelial function), muscle mass (calf circumference adjusted for body mass index) and function (knee extension strength, 6-meter fast gait speed). Multivariable regression analyses for associates of muscle mass/function controlled for demographics and cardiometabolic risk factors. Among 336 participants (median age 62 years, 55.1% male, 3.6% sarcopenia), cIMT, aortic and carotid stiffness inversely correlated with muscle mass, strength and gait speed; cIMT remained independently associated with gait speed (ß=-0.26) in multivariable analyses. Age and sex significantly modified the relationship between subclinical vasculopathy and muscle mass/function. Associations, only found in those aged ≥70, included cIMT with gait speed (ß=-0.48) and knee strength (ß=-9.33), and aortic augmentation index and aortic stiffness composite z-score with gait speed (ß=-0.11 and ß=-0.19 respectively). Among males, cIMT correlated with gait speed (ß=-0.31). The association of subclinical vasculopathy with skeletal muscle mass and function in asymptomatic adults ≥55 years is best reflected by cIMT. The roles of mediating pathways deserve further evaluation.

Outcome trends in people with heart failure, type 2 diabetes mellitus and chronic kidney disease in the UK over twenty years.

BACKGROUND: Heart failure (HF) together with type 2 diabetes (T2D) and chronic kidney disease (CKD) are major pandemics of the twenty first century. It is not known in people with new onset HF, what the distinct and combined associations are between T2D and CKD comorbidities and cause-specific hospital admissions and death, over the past 20 years. METHODS: An observational study using the UK Clinical Practice Research Datalink linked to the Hospital Episode Statistics in England (1998-2017). Participants were people aged ≥30 years with new onset HF. Exposure groups were HF with: (i) no T2D and no CKD (reference group); (ii) CKD-only (estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2); (iii) T2D-only; (iv) T2D and CKD. CKD severity groups were: CKD-3a (eGFR 45-59); CKD-3b (30-44); CKD-4 (15-29); CKD-5 (<15). Outcomes were cardiovascular and non-cardiovascular hospitalisations and all-cause death. FINDINGS: In 87,709 HF patients (mean age, 78 years; 49% female), 40% had CKD-only, 12% T2D-only, and 16% both. Age-standardised first-year CVD hospitalisation rates were significantly higher in HF patients with CKD-only (46.4; 95% CI 44.9,47.9 per 100 person years) and T2D-only (49.2; 46.7,58.8) than in the reference group (35.1; 34.0,36.1); the highest rate was in patients with T2D-CKD-5: 89.1 (65.8,112.4). Similar patterns were observed for non-CVD hospitalisations and deaths. Group differences remained significant after adjustment for potential confounders. Median survival was highest in the reference (4.4 years) and HF-T2D-only (4.1 years) groups, compared to HF-CKD-only (2.2 years). HF-T2D-CKD group survival ranged from 2.8 (CKD-3a) to 0.7 years (CKD-5). Over time, CVD hospitalisation rates significantly increased for HF-CKD-only (+26%) and reduced (-24%) for HF-T2D-only groups; no reductions were observed in any of the HF-T2D-CKD groups. Trends were similar for non-CVD hospitalisations and death: whilst death rates significantly reduced for HF-T2D-only (-37%), improvement was not observed in any of the T2D-CKD groups. INTERPRETATION: In a cohort of people with new onset HF, hospitalisations and deaths are high in patients with T2D or CKD, and worst in those with both comorbidities. Whilst outcomes have improved over time for patients with HF and comorbid T2D, similar trends were not seen in those with comorbid CKD. Strategies to prevent and manage CKD in people with HF are urgently needed. FUNDING: NIHR fellowship [reference: NIHR 30011].

Machine learning versus classical electrocardiographic criteria for echocardiographic left ventricular hypertrophy in a pre-participation cohort.

BACKGROUND: Classical electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH) are well studied in older populations and patients with hypertension. Their utility in young pre-participation cohorts is unclear. AIMS: We aimed to develop machine learning models for detection of echocardiogram-diagnosed LVH from ECG, and compare these models with classical criteria. METHODS: Between November 2009 and December 2014, pre-participation screening ECG and subsequent echocardiographic data was collected from 17 310 males aged 16 to 23, who reported for medical screening prior to military conscription. A final diagnosis of LVH was made during echocardiography, defined by a left ventricular mass index >115 g/m2. The continuous and threshold forms of classical ECG criteria (Sokolow-Lyon, Romhilt-Estes, Modified Cornell, Cornell Product, and Cornell) were compared against machine learning models (Logistic Regression, GLMNet, Random Forests, Gradient Boosting Machines) using receiver-operating characteristics curve analysis. We also compared the important variables identified by machine learning models with the input variables of classical criteria. RESULTS: Prevalence of echocardiographic LVH in this population was 0.82% (143/17310). Classical ECG criteria had poor performance in predicting LVH. Machine learning methods achieved superior performance: Logistic Regression (area under the curve [AUC], 0.811; 95% confidence interval [CI], 0.738-0.884), GLMNet (AUC, 0.873; 95% CI, 0.817-0.929), Random Forest (AUC, 0.824; 95% CI, 0.749-0.898), Gradient Boosting Machines (AUC, 0.800; 95% CI, 0.738-0.862). CONCLUSIONS: Machine learning methods are superior to classical ECG criteria in diagnosing echocardiographic LVH in the context of pre-participation screening.

An East-West comparison of self-care barriers in heart failure.

BACKGROUND: Barriers in heart failure self-care contribute to heart failure hospitalizations, but geographic differences have not been well-studied. We aimed to compare self-care barriers in heart failure patients managed at tertiary centers in an Eastern (Singapore) versus a Western (USA) nation. METHODS: Acute heart failure patients were prospectively assessed with a standardized instrument comprising of 47 distinct self-care barriers. The multi-equation generalized structural equation model was used to evaluate for geographic differences in barriers experienced, and association of barriers with outcomes. RESULTS: Patient-related factors accounted for six out of 10 most prevalent self-care barriers among the 90 patients, with a median number of 11 barriers reported per patient. The Western patients reported a higher level of barriers when compared with their Eastern counterparts (median (interquartile range) 15 (9-24) versus 9 (4-16), p=0.001), after adjusting for demographics and co-morbidities. Many of these differences could be explained by geographic differences between the countries. There was no significant difference identified in all-cause mortality (19.4% versus 10.2%) and heart failure re-hospitalization (41.9% versus 45.8%) at six months between the groups. CONCLUSIONS: Self-care barriers are highly prevalent among acute heart failure patients, and differ substantially between East and West, but were not associated with geographic differences in outcomes.

The Singapore Heart Failure Risk Score: Prediction of Survival in Southeast Asian Patients.

INTRODUCTION: Numerous heart failure risk scores have been developed but there is none for Asians. We aimed to develop a risk calculator, the Singapore Heart Failure Risk Score, to predict 1- and 2-year survival in Southeast Asian patients hospitalised for heart failure. MATERIALS AND METHODS: Consecutive patients admitted for heart failure were identified from the Singapore Cardiac Databank Heart Failure registry. The follow-up was 2 to 4 years and mortality was obtained from national registries. RESULTS: The derivation (2008-2009) and 2 validation cohorts (2008-2009, 2013) included 1392, 729 and 804 patients, respectively. Ten variables were ultimately included in the risk model: age, prior myocardial infarction, prior stroke, atrial fibrillation, peripheral vascular disease, systolic blood pressure, QRS duration, ejection fraction and creatinine and sodium levels. In the derivation cohort, predicted 1- and 2-year survival was 79.1% and 68.1% compared to actual 1- and 2-year survival of 78.2% and 67.9%. There was good agreement between the predicted and observed mortality rates (Hosmer-Lemeshow statistic = 14.36, P = 0.073). C-statistics for 2-year mortality in the derivation and validation cohorts were 0.73 (95% CI, 0.70-0.75) and 0.68 (95% CI, 0.64-0.72), respectively. CONCLUSION: We provided a risk score based on readily available clinical characteristics to predict 1- and 2-year survival in Southeast Asian patients hospitalised for heart failure via a simple online risk calculator, the Singapore Heart Failure Risk Score.

Cornell product is an ECG marker of heart failure with preserved ejection fraction.

OBJECTIVE: ECG markers of heart failure (HF) with preserved ejection fraction (HFpEF) are lacking. We hypothesised that the Cornell product (CP) is a risk marker of HFpEF and has prognostic utility in HFpEF. METHODS: CP =[(amplitude of R wave in aVL+depth of S wave in V3)×QRS] was measured on baseline 12-lead ECG in a prospective Asian population-based study of 606 healthy controls (aged 55±10 years, 45% men), 221 hypertensive controls (62±9 years, 58% men) and 242 HFpEF (68±12 years, 49% men); all with EF ≥50% and followed for 2 years for all-cause mortality and HF hospitalisations. RESULTS: CP increased across groups from healthy controls to hypertensive controls to HFpEF, and distinguished between HFpEF and hypertension with an optimal cut-off of ≥1800 mm*ms (sensitivity 40%, specificity 85%). Age, male sex, systolic blood pressure (SBP) and heart rate were independent predictors of CP ≥1800 mm*ms, and CP was associated with echocardiographic E/e' (r=0.27, p<0.01) and left ventricular mass index (r=0.46, p<0.01). Adjusting for clinical and echocardiographic variables and log N-terminal pro B-type natriuretic peptide (NT-proBNP), CP ≥1800 mm*ms was significantly associated with HFpEF (adjusted OR 2.7, 95% CI 1.0 to 7.0). At 2-year follow-up, there were 29 deaths and 61 HF hospitalisations, all within the HFpEF group. Even after adjusting for log NT-proBNP, clinical and echocardiographic variables, CP ≥1800 mm*ms remained strongly associated with a higher composite endpoint of all-cause mortality and HF hospitalisations (adjusted HR 2.1, 95% CI 1.2 to 3.5). CONCLUSION: The Cornell product is an easily applicable ECG marker of HFpEF and predicts poor prognosis by reflecting the severity of diastolic dysfunction and LV hypertrophy.

Prescribing patterns of evidence-based heart failure pharmacotherapy and outcomes in the ASIAN-HF registry: a cohort study.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), ß blockers, and mineralocorticoid receptor antagonists (MRAs) are of proven benefit and are recommended by guidelines for management of patients with heart failure and reduced ejection fraction (HFrEF). We aimed to examine the first prospective multinational data from Asia on prescribing patterns of guideline-directed medical therapies and analyse its effect on outcomes. METHODS: In the prospective multinational ASIAN-HF registry (with enrolment from 46 centres in 11 countries in Asia), we enrolled patients aged 18 years or older, with symptomatic heart failure (stage C, with at least one episode of decompensated heart failure in the past 6 months that resulted in admission to hospital or was treated in an outpatient clinic) and left ventricular systolic dysfunction (ejection fraction ≤40% on baseline echocardiography, consistent with 2016 European Society of Cardiology guidelines). We excluded patients with heart failure caused by severe valvular heart disease, life-threatening comorbidity with a life expectancy of less than 1 year, who were unable or unwilling to give consent, or who had concurrent participation in a clinical trial. Patients were followed up for 3 years for the outcomes of death and cause-specific admittance to hospital. Primary outcomes were uptake of guideline-directed medical therapies (as proportions) by therapeutic class, achieved doses as proportions of guideline-recommended doses, and their association with 1-year composite outcome of all-cause death or admittance to hospital because of heart failure. This study is registered with ClinicalTrials.gov, number NCT01633398. FINDINGS: Between Oct 1, 2012, and Dec 31, 2015, we enrolled 5276 patients with HFrEF (mean age 59·6 years [SD 13·2], 77% men, body-mass index 24·9 kg/m2 [5·1], 33% New York Heart Association class III or IV). Follow-up data were available for 4544 (90%) of 5061 eligible patients taking medication for heart failure, with median follow-up of 417 days (IQR 214-735). ACE inhibitors or ARBs were prescribed to 3868 (77%) of 5005 patients, ß blockers to 3975 (79%) of 5061, and MRAs to 2998 (58%) of 5205, with substantial regional variation. Guideline-recommended dose was achieved in only 17% of cases for ACE inhibitors or ARB, 13% for ß blockers, and 29% for MRAs. Country (all three drug classes), increasing body-mass index (ACE inhibitors or ARBs and MRAs), and in-patient recruitment (ACE inhibitors or ARBs and ß blockers) were associated with attainment of guideline-recommended dose (all p<0·05). When adjusted for indication bias, increasing drug doses, from low dose (1-<25% of guideline-recommended dose) upwards were associated with lower hazards of a 1-year composite outcome for ACE inhibitors or ARBs and ß blockers compared with non-users. The lowest adjusted hazards were in the group that attained guideline-recommended doses above 50% (hazard ratio [HR] 0·54, 95% CI 0·50-0·58 for ACE inhibitors or ARBs [50-99·9%]; HR 0·47, 0·46-0·50 for ß blockers, and HR 0·77, 0·72-0·81 for MRAs [≥100%]). INTERPRETATION: Guideline-directed medical therapies at recommended doses are underutilised in patients with HFrEF. Improved uptake and uptitration of guideline-directed medical therapies are needed for better patient outcomes. FUNDING: National Medical Research Council (Singapore), A*STAR Biomedical Research Council ATTRaCT program, Boston Scientific Investigator Sponsored Research program, and Bayer.

Real-world use and modeled impact of glucose-lowering therapies evaluated in recent cardiovascular outcomes trials: An NCDR® Research to Practice project.

Aims Recent trials (EMPA-REG OUTCOME and Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results [LEADER]) have shown improved cardiovascular (CV) mortality with specific currently available glucose-lowering medications (empagliflozin and liraglutide, respectively), but were limited to selected patient populations. We sought to evaluate the current use and potential real-world impact of empagliflozin (and other sodium-glucose co-transporter 2 inhibitors [SGLT2is]) and liraglutide (and other glucagonlike peptide-1 receptor agonist [GLP-1 RAs]) among patients in the Diabetes Collaborative Registry (DCR). Methods and results We evaluated 182,525 patients from the DCR - a large, US-based outpatient registry of individuals with type 2 diabetes from 313 sites that included cardiology, endocrinology and primary care practices. Among these patients, 26.2% met major eligibility criteria for EMPA-REG OUTCOME and 48.0% met major eligibility criteria for LEADER. Of these potentially eligible patients, only a small minority were actually prescribed these agents: 5.2% on an SGLT2i and 6.0% on a GLP-1 RA, respectively. Patients receiving these studied medications or medication classes, in general, had lower CV disease burden compared with those not on these agents. Assuming similar risk reductions as in the clinical trials, if all potentially trial-eligible patients in the DCR were treated for 1 year with empagliflozin (or other SGLT2is, assuming a class effect) or liraglutide (or other GLP-1 RAs, assuming a class effect), this may have prevented 354 CV deaths, 231 heart failure hospitalizations, 329 CV deaths and 247 myocardial infarctions, respectively. Conclusion In a large, US-based outpatient registry, we found a significant number of patients would have been potentially eligible for glucose-lowering agents that demonstrated CV benefit in recent clinical trials. In view of these findings, a broader and better-targeted use of these medications in evidence-based patient populations should be considered.

Diabetic cardiomyopathy: An expression of stage B heart failure with preserved ejection fraction.

Heart failure is now recognized as a progressive disease in which patients transition through the stages of being at risk of heart failure (stage A), to asymptomatic structural heart disease (stage B), to clinical manifestations of heart failure (stage C) and finally end-stage or refractory heart failure (stage D). This review outlines the key role of diabetes mellitus as a stage A risk factor for heart failure with preserved ejection fraction, and asymptomatic diabetic cardiomyopathy, referring to the presence of left ventricular diastolic dysfunction in diabetic patients without coronary artery disease, hypertension or other potential aetiologies, as an expression of stage B heart failure with preserved ejection fraction at high risk of transitioning to symptomatic stage C heart failure with preserved ejection fraction. The data presented call for better recognition of the unique phenotype of diabetic cardiomyopathy with preserved ejection fraction and elevated diastolic stiffness as a manifestation of stage B heart failure with preserved ejection fraction that should be targeted for risk management and preventive strategies.