Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF). However, their effects on cardiac structure and function in HFrEF are uncertain. Methods: We designed a multicenter randomized, double-blind, placebo-controlled trial to investigate the cardiac effects of empagliflozin in patients in NYHA functional class II to IV with a left ventricular (LV) ejection fraction ≤40% and type 2 diabetes or prediabetes. Patients were randomized 1:1 to empagliflozin 10 milligrams once daily or placebo, stratified by age (<65 and ≥65 years) and glycemic status (diabetes or prediabetes). The co-primary outcomes were change from baseline to 36 weeks in LV end-systolic volume indexed to body surface area (LVESVi) and LV global longitudinal strain (LV GLS) measured using cardiovascular magnetic resonance (CMR). Secondary efficacy outcomes included other CMR measures (LVEDVi, LVEF), diuretic intensification, symptoms (Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS)), 6-minute walk distance (6MWD), B-lines on lung ultrasound and biomarkers (including NT-proBNP). Results: From April 2018 to August 2019, 105 patients were randomized: 77 (73.3%) male, mean age 68.7 [SD 11.1] years, 82 (78.1%) diabetes and 23 (21.9%) prediabetes, mean LVEF 32.5% [9.8%], and 81 (77.1%) NYHA II and 24 (22.9%) NYHA III. Patients received standard treatment for HFrEF. Compared with placebo, empagliflozin reduced LVESVi by 6.0 (-10.8 to -1.2) ml/m 2 (p=0.015). There was no difference in LV GLS. Empagliflozin reduced LVEDVi by 8.2 (-13.7 to -2.6) ml/m 2 (p=0.0042) and reduced NT-proBNP by 28 (2 to 47) %, p=0.038. There were no between-group differences in other CMR measures, KCCQ-TSS, 6MWD or B-lines. Conclusions: The SGLT2 inhibitor empagliflozin reduced LV volumes in patients with HFrEF and type 2 diabetes or prediabetes. Favorable reverse LV remodeling may be a mechanism by which SGLT2 inhibitors reduce HF hospitalization and mortality in HFrEF. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique Identifier: NCT03485092.

Background: The selection of patients for cardiac transplantation is notoriously difficult. We have demonstrated that N-terminal brain natriuretic peptide (NT-proBNP) is a powerful predictor of mortality in advanced heart failure and is superior to the traditional markers of chronic heart failure (CHF) severity. However, the comparative prognostic power of endothelin-1 (Et-1), adrenomedullin (Adm) and tumour necrosis factor-alpha (TNF-a) in this patient group is unknown. Methods and results: We prospectively studied 150 consecutive patients with advanced CHF referred for consideration of cardiac transplantation. Blood samples for NT-proBNP, Et-1, Adm and TNF-a analysis were taken at recruitment and patients followed up for a median of 666 days. The primary endpoint of all-cause mortality was reached in 25 patients and the secondary endpoint of all-cause mortality or urgent cardiac transplantation in 29 patients. The median values for NT-proBNP, Et-1, Adm and TNF-a were 1494 pg/ml [interquartile range 530-3930], 0.39 fmol/ml [0.10-1.24], 94 pg/ml and 2.0 pg/ml [0-18.5] respectively. The only univariate and multivariate predictor of all-cause mortality (v 2 =26.95, pb0.0001), or the secondary endpoint of all-cause mortality or urgent transplantation (v 2 =31.23, pb0.0001), was an NT-proBNP concentration above the median value. Conclusion: A single measurement of NT-proBNP in patients with advanced CHF can help identify patients at the highest risk of death, and is a better prognostic marker than Et-1, Adm and TNF-a.

SummaryPrevalence of heart failure is increasing, especially in the elderly population. Noncardiac comorbidities complicate heart failure care and are increasingly common in elderly patients with reduced or preserved ejection fraction heart failure, owing to prolongation of patient's lives by advances in chronic heart failure (CHF) management. Common comorbidities include respiratory disease, renal dysfunction, anemia, arthritis, obesity, diabetes mellitus, cognitive dysfunction, and depression. These conditions contribute to the progression of the disease and may alter the response to treatment, partly as polypharmacy is inevitable in these patients. Cardiologists and other physicians caring for patients with CHF need to be vigilant to comorbid conditions that complicate the care of these patients. There is now more guidance on management of noncardiac comorbidities in heart failure, and this article contains a comprehensive review of the most recent updates on management of noncardiac comorbidities in CHF.

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A 73-year-old woman presented with acute shortness of breath and exacerbation of chronic back pain. She was diagnosed with pulmonary oedema and a non-ST-elevation myocardial infarction following chest X-ray, ECG and high sensitivity troponin levels. She subsequently underwent coronary angioplasty with deployment of drug-eluting stents to her circumflex and left anterior descending arteries and was started on aspirin and clopidogrel for her dual antiplatelet therapy. Unfortunately, following the procedure, she gradually lost power and sensation in both lower limbs. MRI of her spine confirmed an extradural haematoma causing thoracic cord compression. She was managed conservatively following discussions with neurosurgeons and developed further complications secondary to her immobility.