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The feasibility and value of linking electrocardiogram (ECG) data to longitudinal population-level administrative health data to facilitate the development of a learning healthcare system has not been fully explored. We developed ECG-based machine learning models to predict risk of mortality among patients presenting to an emergency department or hospital for any reason. Using the 12-lead ECG traces and measurements from 1,605,268 ECGs from 748,773 healthcare episodes of 244,077 patients (2007–2020) in Alberta, Canada, we developed and validated ResNet-based Deep Learning (DL) and gradient boosting-based XGBoost (XGB) models to predict 30-day, 1-year, and 5-year mortality. The models for 30-day, 1-year, and 5-year mortality were trained on 146,173, 141,072, and 111,020 patients and evaluated on 97,144, 89,379, and 55,650 patients, respectively. In the evaluation cohort, 7.6%, 17.3%, and 32.9% patients died by 30-days, 1-year, and 5-years, respectively. ResNet models based on ECG traces alone had good-to-excellent performance with area under receiver operating characteristic curve (AUROC) of 0.843 (95% CI: 0.838–0.848), 0.812 (0.808–0.816), and 0.798 (0.792–0.803) for 30-day, 1-year and 5-year prediction, respectively; and were superior to XGB models based on ECG measurements with AUROC of 0.782 (0.776–0.789), 0.784 (0.780–0.788), and 0.746 (0.740–0.751). This study demonstrates the validity of ECG-based DL mortality prediction models at the population-level that can be leveraged for prognostication at point of care.

With recent advances in the pharmacological management of type 2 diabetes mellitus (T2DM), there is a growing need to understand which patients optimally benefit from these novel therapies. Various clinical clustering methodologies have emerged that utilise data-agnostic strategies to categorise patients that have similar clinical characteristics and outcomes; broadly, this characterisation is termed phenotyping. In patients with T2DM, we aimed to describe patient characteristics from phenotype studies, their cardiovascular risk profiles and the impact of antihyperglycemic treatment. Numerous phenotypic studies have been undertaken that have utilised a combination of clinical, biochemical, imaging and genetic variables. Each of these has produced phenotypes that display a spectrum of cardiovascular risk. Studies that aimed to describe pathophysiological phenotypes generally identified five phenotypes: autoimmune phenotype, insulin-related phenotypes (including permutations of insulin deficiency and resistance), obesity phenotype, ageing phenotype, and a sex-related phenotype. Studies examining risk profiles have demonstrated that across such phenotypes there is a spectrum of risk for diabetic complications. Few studies have examined treatment effects across these phenotypes, and thus provide little insights towards making phenotype-guided treatment decisions Clustering analyses in patients with T2DM have identified distinct phenotypes with unique risk profiles. Further studies are needed that harness the use of clinical, biochemical, imaging and genetic data to explore therapeutic heterogeneity and response to antihyperglycemic treatment across the spectrum of patient phenotypes.

This study examined the prevalence of pre-hypertension (PHT) and hypertension (HT) in urban youth, and assessed the effects of sodium intake and obesity on blood pressure (BP) by ethnicity. A convenience sample of 557 multiethnic youth, aged 11–23 years, was recruited from 12 schools and institutions in Edmonton, Alberta, Canada. Participants were divided by self-identified ethnicity into four groups (Indigenous, African and Middle Eastern (AME), Asian, and European). Between October 2013 and March 2014, one-on-one interviews were conducted to collect data on demographics, physical activity, diet, and Body Mass Index (BMI). BP was obtained at two different times during the interview and measured a third time in cases of high variability. The standard deviation scores (SDS) of systolic BP (SBP) and diastolic BP (DBP) were used to estimate associations with sodium intake (per 1000 mg/day). Overall, 18.2% and 5.4% of the participants had PHT and HT, respectively. Indigenous and AME participants showed the highest rates of PHT (23.1%). Indigenous and European participants showed higher rates of HT (8.3% and 5.3%, respectively) than other ethnic groups (AME = 4.4%, Asian = 3.9%). There was a positive association between 1000 mg/day increase in sodium intake and SDS of SBP by 0.041 (95% CI 0.007–0.083; p = 0.04) among pre-hypertensive participants. Over 85% of participants exceeded the recommended dietary sodium intake. Mean BMI and dietary sodium intake were higher among pre-hypertensive participants (4219 mg/day) than normotensive (3475 mg/day). The prevalence of HT varied by ethnicity. High dietary sodium intake was of concern. There is a need for culturally-tailored, population-based interventions to reduce sodium intake.

Patients hospitalized for heart failure (HF) remain at high risk for early readmission. A post hoc analysis was performed of the biomarker substudy of the ASCEND-HF trial. An in-hospital congestion score was derived using orthopnea, pedal edema, and NT-proBNP levels. Its added prognostic value beyond traditional risk factors was assessed by determining the net reclassification index (NRI). Study participants (n = 884) had a median age (years) of 67 (55–77), 68% were male, and the median (25th–75th) ejection fraction (%) was 26 (20–40). After adjustment, increasing congestion score was associated with 30-day all-cause mortality or HF hospitalization (odds ratio = 1.51, 95% confidence interval [CI] 1.28–1.77, p

Background Global longitudinal strain (GLS), most commonly measured at the endocardium, has been shown to be superior to left ventricular (LV) ejection fraction (LVEF) for the identification of systolic dysfunction and prediction of outcomes in heart failure (HF). We hypothesized that strains measured at different myocardial layers (endocardium = ENDO, epicardium = EPI, average = AVE) will have distinct diagnostic and predictive performance for patients with HF. Methods Layer-specific GLS, layer-specific global circumferential strain (GCS) and global radial strain (GRS) were evaluated by cardiovascular magnetic resonance imaging (CMR) feature tracking in the Alberta HEART study. A total of 453 subjects consisted of healthy controls (controls, n = 77), at-risk for HF (at-risk, n = 143), HF with preserved ejection fraction (HFpEF, n = 87), HF with mid-range ejection fraction (HFmrEF, n = 88) and HF with reduced ejection fraction (HFrEF, n = 58). For outcomes analysis, CMR-derived imaging parameters were adjusted with a base model that included age and N-terminal prohormone of b-type natriuretic peptide (NT-proBNP) to test their independent association with 5-year all-cause mortality. Results GLS_EPI distinguished all groups with preserved LVEF (controls − 16.5 ± 2.4% vs. at-risk − 15.5 ± 2.7% vs. HFpEF − 14.1 ± 3.0%, p Conclusion Global strains measured on endocardium, epicardium or averaged across the wall thickness are not equivalent for the identification of systolic dysfunction or outcomes prediction in HF. The endocardium-specific strains were shown to have poorest all-around performance. GLS_AVE and GRS were the only CMR parameters to be significantly associated with 5-year all-cause mortality in multivariable analysis. GLS_EPI and GRS, as well as the difference in endocardial and epicardial strains, were sensitive to systolic dysfunction among HF patients with normal LVEF (> 55%), in whom lower strains were associated with increased concentricity.

Introduction TRV027, a 'biased' ligand of the angiotensin II type 1 receptor (AT1R), did not affect a composite clinical outcome at 30 days in a phase 2b acute heart failure (AHF) trial (BLAST-AHF).Methods Post-hoc analyses from BLAST-AHF (n = 618) examined the effects of TRV027 by baseline systolic blood pressure (SBP) on changes in renal function and 180-day outcomes. Interactions between baseline SBP and select endpoints were identified utilizing a subpopulation treatment effect pattern plots (STEPP) analysis, then grouping of patients by SBP tertile: = 127 to = 140 mmHg.Results A trend towards increased creatinine in the first 3 days was noted in the lower SBP tertile, while in those in the higher two tertiles, TRV027, especially the 1 mg/h dose, reduced creatinine at days 5 and 30. Beneficial effects on 180-day all-cause mortality and cardiovascular (CV) death or readmission were observed in the two higher SBP tertiles (SBP >= 127 mmHg) in the TRV027 1 mg/h dose group (all-cause mortality HR 0.39, 95% CI 0.14-1.06, p = 0.056; CV death or HF/RF rehospitalization HR 0.53, 95% CI 0.28-1.01, p = 0.049), while more adverse outcomes were observed in patients in the lower SBP tertile.Conclusions This post-hoc analysis of the BLAST-AHF study suggests contrasting effects of TRV027 by baseline SBP, with trends towards lower 180-day event rates in patients enrolled with higher baseline SBP, especially when given lower doses of TRV027.

Cognitive impairment (CI) is common in older adults with heart failure (HF). The prevalence of CI is higher among patients with HF than in those without. The spectrum of CI in HF is similar to that observed in the general population and may range from delirium to isolated memory or non-memory-related deficits to dementia. Both HF with reduced ejection fraction and HF with preserved ejection fraction have been associated with defects in different domains of cognition. Numerous risk factors have been shown to contribute to CI in HF. Additionally, various pathophysiological mechanisms related to HF can contribute to cognitive decline. These conditions are not routinely screened for in clinical practice settings with HF populations, and guidelines on optimal assessment strategies are lacking. Validated tools and criteria should be used to differentiate acute cognitive decline (delirium) from chronic cognitive decline such as mild cognitive impairment and dementia. CI in HF has been associated with higher rates of disability and impairment in self-care activities that may in turn increase healthcare cost, hospital readmission and mortality. Early detection of CI may improve clinical outcomes in older adults with HF. Appropriate HF management strategies may also help to reduce CI in patients with HF, and future research is needed to develop and test newer and more effective interventions to improve outcomes in patients with HF and CI.

Eplerenone has been demonstrated as being cost effective for the treatment of patients with systolic heart failure (HF) and mild symptoms in several jurisdictions; however, its cost effectiveness is unknown in the context of Alberta, Canada.We used a discrete-event simulation model to compare costs and outcomes between standard care and standard care plus eplerenone for the treatment of HF with mild symptoms. We used Alberta data (whenever possible) together with a healthcare perspective, a lifetime horizon, and 3 % annual discount rate for analyses.Clinically, eplerenone prevented HF hospitalizations, atrial fibrillations, and cardiovascular (CV) deaths, but incurred more adverse events and device implantations than standard care. The remaining life of patients receiving eplerenone was 7.08 versus 5.83 years for those receiving standard care. Eplerenone gained 1.25 life-years and 1.18 quality-adjusted life-years (QALYs), with an incremental cost of $Can7200. Therefore, the incremental cost-effectiveness ratio (ICER) was $Can5700 per life-year gained and $Can6100 per QALY gained.Given the most cited ICER threshold is $Can50,000, the use of eplerenone as an adjunct to standard care for treating patients with systolic HF and mild symptoms is cost effective in the context of Alberta. Eplerenone would cost the Alberta health system about $Can4.6 million a year in drug costs. Incorporating reductions in health services utilization associated with eplerenone, the budget impact is smaller. For the first year, the use of eplerenone is cost saving and for 5 years the cost is approximately $Can6 million.

The CKD-EPI equation is more accurate than the MDRD equation in the general population. We performed this study to establish whether chronic kidney disease (CKD) is commonly recognized by clinicians and whether the CKD-EPI equation improves prognosis estimation in patients with chronic cardiovascular disease (CVD). We analyzed data on 12394 CVD patients consecutively examined at the Cardiovascular Center of Trieste (Italy) between November 2009 and October 2013. The outcomes were all-cause death and a composite outcome of death/hospitalization for CV events (D+cvH). CKD-EPI formula reclassified 1786 (14.4 %) patients between KDIGO categories compared to the MDRD: 2.3 % (n = 280) placed in a lower risk and 12.1 % (n = 1506) into a higher risk group. CKD, defined as eGFR-CKD-EPI formula 60 but eGFR-CKD-EPI formula

Dietary management of heart failure (HF) has largely been focused on sodium and fluid restrictions. Although safety and efficacy of these interventions in HF remain unclear, a daily sodium intake between 2000 and 3000 mg/day appears to be safe in these patients. Ongoing clinical research will inform on the safety and efficacy of a more restrictive sodium intake to less than 1500 mg/day. Data shows that routine fluid restriction in HF regardless of symptoms may be unnecessary; however, in patients with signs of congestion, fluid restriction to 2.0 L/day may be advisable. Recently, more attention has been paid to other nutritional aspects of HF beyond sodium and fluid intake, although there is still little evidence available to guide nutritional management of HF. Assuring that patients meet daily requirements for key micronutrients, such as calcium, magnesium, potassium, folate, vitamin E, vitamin D, zinc, and thiamine, is essential in order to prevent deficiencies. More appropriate macronutrient composition of the diet is still to be determined; however, a diet containing 50-55% carbohydrates, 25-30% fat, and 15-20% protein seems acceptable for patients with HF with or without non-end-stage renal disease. Additionally, increased protein intake may be considered in malnourished/cachectic patients. Consulting a registered dietitian is especially helpful for patients with recent HF exacerbations or for patients with multiple comorbidities who may need to follow several dietary restrictions and may benefit of individualized dietary counseling in order to ensure appropriate intake of energy, protein, and micronutrients. Today, there are still several knowledge gaps in guiding the dietary management of HF. In this article, we review current recommendations for the dietary management of HF and the evidence supporting this practice.

Patients with atrial fibrillation (AF) and heart failure (HF) are at risk for stroke, and progress in anticoagulation has led to new options for these patients. Patients in sinus rhythm may benefit from antiplatelet agents or anticoagulants, but much work remains to establish efficacy and safety. Additional progress is needed, including better tools for risk stratification and clarity regarding the need for antiplatelet agents in combination with anticoagulants for those with other vascular diseases. Clinical Pharmacology & Therapeutics (2013); 94 4, 435–438. doi:10.1038/clpt.2013.133

Patients who survive a myocardial infarction (MI) are at increased risk of sudden death due to fatal ventricular arrhythmias. Implantable cardioverter-defibrillators (ICDs) reduce mortality in appropriately selected patients with heart failure and left ventricular dysfunction, regardless of etiology. Post hoc analyses from landmark trials have evaluated the effect of time (both since MI and duration of nonischemic cardiomyopathy) before ICD implantation on the efficacy of ICD therapy. Time remains a clinically important variable in the decision of if and when to implant an ICD. Future trials should focus on invasive and/or noninvasive risk stratification of patients with ischemic and nonischemic cardiomyopathy for better identification of those who would benefit from early ICD implantation, and those in whom a watch and wait approach is appropriate.

Coronary plaque rupture is associated with a systemic inflammatory response. The relationship between baseline N-terminal pro B-type natriuretic peptide (NT-proBNP), a prognostic marker in patients with acute coronary syndromes, and systemic inflammatory mediators in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) is not well described. Of 5,745 STEMI patients treated with primary PCI in the APEX-AMI trial, we evaluated the relationship between baseline NT-proBNP levels and baseline levels of inflammatory markers and markers of myonecrosis in a subset of 772 who were enrolled in a biomarker substudy. Spearman correlations (r (s)) were calculated between baseline NT-proBNP levels and a panel of ten systemic inflammatory biomarkers. Interleukin (IL)-6, a pro-inflammatory cytokine, was significantly positively correlated with NT-proBNP (r (s) = 0.317, P0.001). In a sensitivity analysis excluding all heart failure patients, the correlation between baseline IL-6 and NT-proBNP remained significant (n = 651, r (s) = 0.296, P0.001). A positive association was also observed with high sensitivity C-reactive protein (r (s) = 0.377, P0.001) and there was a weak negative correlation with the anti-inflammatory cytokine IL-10 (r (s) = -0.109, P = 0.003). No other significant correlations were observed among the other testes inflammatory cytokines and chemokines. In STEMI patients undergoing primary PCI, the pro-inflammatory cytokine IL-6 was modestly correlated with baseline NT-proBNP levels. This relationship remained significant in patients without heart failure. This finding is consistent with pre-clinical and clinical research suggesting that systemic inflammation may influence NT-proBNP expression independently of myocardial stretch.

Heart disease is important in elderly patients. The treatment of myocardial infarction and heart failure are particularly important and will continue to play an important role across the globe. Advances in treatment of myocardial infarction have made tremendous inroads in the short and long term survival of patients, young and old, however, many currently employed strategies have not been tested in patients who are elderly, who paradoxically, form a growing subset of patients with heart disease. A similar paradigm exists in heart failure for both diagnosis and treatment. Attention to this issue is important when selecting treatment strategies and a focus on the goals of care is critical when decisions for care must be undertaken.