Temporal trends in mortality, heart failure hospitalisation, and stroke in heart failure patients with and without atrial fibrillation: a nationwide study from 1997-2018 on 152,059 patients.

AIMS: We aimed to investigate temporal trends in all-cause mortality, heart failure (HF) hospitalisation, and stroke from 1997 to 2018 in patients diagnosed with both HF and atrial fibrillation (AF). METHODS AND RESULTS: From Danish nationwide registers, we identified 152 059 patients with new-onset HF between 1997 and 2018. Patients were grouped according to year of new-onset HF and AF-status: Prevalent AF (n = 34 734), New-onset AF (n = 12 691), and No AF (n = 104 634). Median age decreased from 76 to 73 years between 1997 and 2018. The proportion of patients with prevalent or new-onset AF increased from 24.7% (n = 9256) to 35.8% (n = 14 970). Five-year risk of all-cause mortality went from 69.1% (CI: 67.9%-70.2%) to 51.3% (CI: 49.9%-52.7%), 62.3% (CI: 60.5%-64.4%) to 43.0% (CI: 40.5%-45.5%), and 61.9% (CI: 61.3%-62.4%) to 36.7% (CI: 35.9%-37.6%) for the Prevalent AF, New-onset AF and No AF-group, respectively. Minimal changes were observed in the risk of HF-hospitalisation. Five-year stroke risk decreased from 8.5% (CI: 7.8%-9.1%) to 5.0% (CI: 4.4%-5.5%) for the prevalent AF group, 8.2% (CI: 7.2%-9.2%) to 4.6% (CI: 3.7%-5.5%) for new-onset AF, and 6.3% (CI: 6.1%-6.6%) to 4.9% (CI: 4.6%-5.3%) for the No AF group. Simultaneously, anticoagulant therapy increased for patients with prevalent (from 42.7% to 93.1%) and new-onset AF (from 41.9% to 92.5%). CONCLUSION: From 1997 to 2018, we observed an increase in patients with HF and co-existing AF. Mortality decreased for all patients, regardless of AF-status. Anticoagulation therapy increased, and stroke risk for patients with AF was reduced to a similar level as patients without AF in 2013-2018.

Prognosis of acute coronary syndrome stratified by cancer type and status - a nationwide cohort study.

BACKGROUND: To investigated the prognosis of the most prevalent cancers (breast-, gastrointestinal-, and lung cancer), according to cancer status (i.e., active-, non-active-, history of-, and no cancer), following first-time of acute coronary syndrome (ACS). METHODS: Danish nationwide registers were used to identify patients with first-time ACS from 2000-2018. Patients were stratified according to cancer type and status. Hazard ratios (HR) estimated by adjusted Cox regression models for 1year all-cause mortality reported. Further absolute risks of 1year cardiovascular versus non-cardiovascular death and 30-day cumulative incidence of coronary angiograms (CAG) was estimated, using the Aalen-Johansen non-parametric method, with competing risk of death. RESULTS: We identified 150,478 (95.7%) with no cancer, 2,370 (1.5%) with history of cancer, 2,712 (1.7%) with non-active cancer and 1,704 (1.1%) with active cancer. Cancer patients were older with more comorbidities than patients with no cancer. When compared with no cancer, we found HRs (95% confidence intervals) of 1.71 (1.44-2.02), 2.47 (2.23-2.73) and 4.22 (3.87-4.60) correspondingly for active breast-, gastrointestinal-, and lung cancer. Increased HRs were also found for non-active cancers, but not for history of cancer. Cardiovascular disease was the leading cause of death in all patients. Among patients with active breast-, gastrointestinal-, and lung cancer 43%, 43%, and 31% underwent CAG, correspondingly, compared with 77% of patients without cancer. CONCLUSIONS: Active- and non-active cancers were associated with an increased 1-year all-cause mortality compared with patients with history of cancer and no cancer. Cardiovascular disease was the leading cause of death; notably CAG was less frequently performed in cancer patients.

The effect of empagliflozin on contractile reserve in heart failure: Prespecified sub-study of a randomized, double-blind, and placebo-controlled trial.

BACKGROUND: Sodium-glucose co-transporter-2 inhibitors improve cardiac structure but most studies suggest no change in left ventricular (LV) systolic function at rest. Whether sodium-glucose co-transporter-2 inhibitors improve LV contractile reserve is unknown. We investigated the effect of empagliflozin on LV contractile reserve in patients with heart failure (HF) and reduced ejection fraction. METHODS: Prespecified sub-study of the Empire HF trial, a double-blind, placebo-controlled, and randomized trial. Patients with LV ejection fraction (LVEF) ≤ 40% on guideline-directed HF therapy were randomized (1:1) to empagliflozin 10 mg or placebo for 12 weeks. The treatment effect on contractile reserve was assessed by low dose dobutamine stress echocardiography. RESULTS: In total, 120 patients were included. The mean age was 68 (SD 10) years, 83% were male, and the mean LVEF was 38 (SD 10) %. Respectively 60 (100%) and 59 (98%) patients in the empagliflozin and placebo groups completed stress echocardiography. No statistically significant effect of empagliflozin was observed for the contractile reserve assessed by LV-GLS (adjusted mean absolute change, empagliflozin vs placebo, 0.7% [95% confidence interval {CI} -0.5 to 2.0, P = .25]) or LVEF (adjusted mean absolute change, empagliflozin vs placebo, 2.2% [95% CI -1.4 to 5.8, P = .22]) from baseline to 12 weeks. LV-GLS contractile reserve was associated with accelerometer-measured daily activity level (coefficient -24 accelerometer counts [95% CI -46 to -1.8, P = .03]). CONCLUSIONS: Empagliflozin for 12 weeks added to guideline-directed HF therapy did not improve LV contractile reserve in patients with HF and reduced ejection fraction.

The effect of empagliflozin on growth differentiation factor 15 in patients with heart failure: a randomized controlled trial (Empire HF Biomarker).

BACKGROUND: Plasma growth differentiation factor-15 (GDF-15) biomarker levels increase in response to inflammation and tissue injury, and increased levels of GDF-15 are associated with increased risk of mortality in patients with heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter-2 (SGLT2) inhibitors, which improve outcome in HFrEF, have been shown to increase plasma GDF-15 in diabetic patients. We aimed to investigate the effect of empagliflozin on GDF-15 in HFrEF patients. METHODS: This Empire HF Biomarker substudy was from the multicentre, randomized, double-blind, placebo-controlled Empire HF trial that included 190 patients from June 29, 2017, to September 10, 2019. Stable ambulatory HFrEF patients with ejection fraction of ≤ 40% were randomly assigned (1:1) to empagliflozin 10 mg once daily, or matching placebo for 12 weeks. Changes from baseline to 12 weeks in plasma levels of GDF-15, high-sensitive C-reactive protein (hsCRP), and high-sensitive troponin T (hsTNT) were assessed. RESULTS: A total of 187 patients who were included in this study, mean age was 64 ± 11 years; 85% male, 12% with type 2 diabetes, mean ejection fraction 29 ± 8, with no differences between the groups. Baseline median plasma GDF-15 was 1189 (918-1720) pg/mL with empagliflozin, and 1299 (952-1823) pg/mL for placebo. Empagliflozin increased plasma GDF-15 compared to placebo (adjusted between-groups treatment effect; ratio of change (1·09 [95% confidence interval (CI), 1.03-1.15]: p = 0.0040). The increase in plasma GDF15 was inversely associated with a decrease in left ventricular end-systolic (R = - 0.23, p = 0.031), and end-diastolic volume (R = - 0.29, p = 0.0066). There was no change in plasma hsCRP (1.09 [95%CI, 0.86-1.38]: p = 0.48) or plasma hsTNT (1.07 [95%CI, 0.97-1.19]: p = 0.18) compared to placebo. Patients with diabetes and treated with metformin demonstrated no increase in plasma GDF-15 with empagliflozin, p for interaction = 0·01. CONCLUSION: Empagliflozin increased plasma levels of GDF-15 in patients with HFrEF, with no concomitant increase in hsTNT nor hsCRP. TRIAL REGISTRATION: The Empire HF trial is registered with ClinicalTrials.gov, NCT03198585.

Rapid Rule-Out of Myocardial Infarction After 30 Minutes as an Alternative to 1 Hour: The RACING-MI Cohort Study.

STUDY OBJECTIVE: The aim of this study was to investigate whether myocardial infarction can be safely ruled in or out after 30 minutes as an alternative to 1 hour. METHODS: This was a prospective, single-center clinical study enrolling patients admitted to the emergency department. Patients with chest pain suggestive of myocardial infarction were eligible for inclusion. There was no walk-in to the emergency department, and patients with highly elevated out-of-hospital troponin were transferred directly to an invasive heart center. High-sensitivity troponin I was measured at admission (0 hour), 30 minutes, 1 hour, and 3 hours. Diagnostic performance was assessed using the sensitivity and negative predictive value (primary endpoints) as measures of ability to rule out myocardial infarction. Specificity and positive predictive value of myocardial infarction were used as measures for the ability to rule in myocardial infarction (secondary endpoints). RESULTS: In total, 1,003 patients qualified for analysis. Median age was 64 (interquartile range 52 to 74) years, and 42% were women. Myocardial infarction was confirmed in 9% of patients. In the validation cohort (n=503), the 0-h/30-min algorithm assigned 242 (48%) patients to rule out, 54 (11%) to rule in, and 207 (41%) to the observational zone. This resulted in a sensitivity of 100% (92.0% to 100%), negative predictive value of 100% (95% confidence interval 98.5% to 100%), specificity of 96.7% (94.7% to 98.2%), and positive predictive value of 72.2% (58.4% to 83.5%). In comparison, the 0-h/1-h algorithm performed with a sensitivity of 100% (92.0% to 100%), negative predictive value of 100% (98.5% to 100%), specificity of 97.2% (95.2% to 98.5%), and positive predictive value of 75.5% (61.7% to 86.2%). CONCLUSION: The accelerated 0-h/30-min algorithm allowed for safe rule-out of myocardial infarction 30 minutes after admission. The rule-in ability of the 0-h/30-min algorithm was comparable to that of the 0-h/1h algorithm.