Aims Despite well-established benefits of sacubitril/valsartan for cardiac reverse remodelling and the prognosis of patients with heart failure with reduced ejection fraction (HFrEF), there are some patients with limited therapeutic response, even with optimal therapy. We assessed the treatment response to sacubitril/valsartan in patients with HFrEF, focusing on the association between reverse remodelling and the prognosis. Methods and results Using a retrospective cohort of consecutive patients with HFrEF treated with sacubitril/valsartan, we compared the time trajectory of cardiac function in 415 patients (1258 echocardiograms), according to the occurrence of cardiovascular death and hospitalization for HF during a median follow-up of 19.1 (interquartile range, 10.9-27.6) months. A higher sacubitril/valsartan dose was associated with a better prognosis, whereas advanced age, diabetes, left ventricular (LV) hypertrophy, left atrial enlargement, and pulmonary hypertension were associated with a worse prognosis. Patients without an event (n = 337; 81.2%) showed LV reverse remodelling (LV ejection fraction ≥45% or LV end-systolic volume reduction by 15% from baseline), which was typically observed within 6 months of sacubitril/valsartan treatment. Reverse remodelling achievement was significantly associated with a better prognosis. However, patients without reverse remodelling had a worse prognosis, as poor as that in patients with HFrEF not treated with sacubitril/valsartan. Conclusions In patients with HFrEF treated with sacubitril/valsartan, LV reverse remodelling reflects the treatment response and predicts the prognosis, whereas a lack of reverse remodelling indicates the lack of treatment benefits. Prediction and assessment of reverse remodelling may facilitate the selection of patients with greater benefits by sacubitril/valsartan.

Although both diabetes mellitus (DM) and underweight are associated with increased risk of tuberculosis (TB), there are limited data evaluating TB risk while considering two factors simultaneously—body mass index (BMI) and DM. A retrospective cohort study was performed with 10,087,903 participants of the Korean National Health Screening Program in 2009. The cohort was followed up to the date of TB incidence, death, or until December 31, 2018. We compared the incidence and risk of TB according to BMI category and DM. During the 7.3-year follow-up duration, the incidence of TB was 0.92 per 1,000 person-years in the normal weight without DM, 2.26 in the normal weight with DM, 1.80 in the underweight without DM, and 5.35 in the underweight with DM. Compared to the normal weight without DM, the normal weight with DM, the underweight without DM, and the underweight with DM showed a 1.51-fold (95% CI, 1.46–1.57), a 2.21-fold (95% CI, 2.14–2.28), and a 3.24-fold (95% CI, 2.95–3.56) increased risk of TB, respectively. However, compared to the normal weight without DM, the severely obese without DM and those with DM showed a 0.37 (95% CI, 0.36–0.38) and a 0.42 (95% CI, 0.36–0.48)-fold decreased risk of TB, respectively. There was no significant joint effect of BMI and DM on the risk of incident TB in the overall population; a synergistic effect of underweight and DM was evident in participants <65 years of age, current smokers, and heavy drinkers. In conclusion, being underweight or DM individually increases the risk of incident TB. Based on our study results, a focused screening of incident TB in patients with DM may be beneficial.

Angiotensin receptor-neprilysin inhibitor (ARNI) and sodium–glucose co-transporter-2 inhibitor (SGLT2i) have shown benefits in diabetic patients with heart failure with reduced ejection fraction (HFrEF). However, their combined effect has not been revealed. We retrospectively identified diabetic patients with HFrEF who were prescribed an ARNI and/or SGLT2i. The patients were divided into groups treated with both ARNI and SGLT2i (group 1), ARNI but not SGLT2i (group 2), SGLT2i but not ARNI (group 3), and neither ARNI nor SGLT2i (group 4). After propensity score-matching, the occurrence of hospitalization for heart failure (HHF), cardiovascular mortality, and changes in echocardiographic parameters were analyzed. Of the 206 matched patients, 92 (44.7%) had to undergo HHF and 43 (20.9%) died of cardiovascular causes during a median 27.6 months of follow-up. Patients in group 1 exhibited a lower risk of HHF and cardiovascular mortality compared to those in the other groups. Improvements in the left ventricular ejection fraction and E/e′ were more pronounced in group 1 than in groups 2, 3 and 4. These echocardiographic improvements were more prominent after the initiation of ARNI, compare to the initiation of SGLT2i. In diabetic patients with HFrEF, combination of ARNI and SGT2i showed significant improvement in cardiac function and prognosis. ARNI-SGLT2i combination therapy may improve the clinical course of HFrEF in diabetic patients.