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Acute heart failure (AHF) is frequent and life-threatening disease. However, innovative AHF therapies have remained limited, and care is based on experts' opinion. Temporal trends and benefits of long-term oral cardiovascular medications on AHF outcomes remain uncertain.

Aims Dipeptidyl peptidase 3 (DPP3) is a protease involved in the degradation of cardiovascular mediators. Its administration has been shown to be associated with impaired cardiac contraction and kidney haemodynamics while its inhibition restored cardiac contraction in a pre‐clinical model of severe heart failure in mice. Circulating DPP3 (cDPP3) was found to be elevated in shock. The present study aims to assess the association between cDPP3 and worsening haemodynamics, namely refractory shock, in a cohort of cardiogenic shock (CS). Methods and results This is an ancillary study of OptimaCC, a prospective, double‐blind, multicentre, randomized study assessing efficacy and safety of catecholamines in 57 patients with CS after acute myocardial infarction. cDPP3 was measured in plasma at inclusion, 24 h, 48 h, and 72 h, and haemodynamic and biological parameters were recorded at inclusion. cDPP3 values were higher in refractory CS than non‐refractory CS at inclusion (median [interquartile range]; 76.1 [37.9–238.7] ng/mL vs. 32.8 [23.9–47.6] ng/mL, P = 0.014), at 24 h (P < 0.001) and up to 48 h (P = 0.027). Furthermore, cDPP3 at inclusion discriminated CS patients who did develop refractory shock vs. non‐refractory with an area under the curve of 0.73 (95% confidence interval [CI] 0.55–0.92). The high cDPP3 group (cDPP3 ≥59.1 ng/mL) at inclusion had a higher Simplified Acute Physiology Score II (SAPS II), lower cardiac index and lower estimated glomerular filtration rate. More importantly, in CS patients with high cDPP3 at inclusion, those who rapidly decreased cDPP3 at 24 h exhibited a striking reduction in the occurrence of refractory shock and death. Conclusion In CS patients, cDPP3 gives an early prediction of outcome, including development of refractory status and/or survival. Clinical Trial Registration: http://clinicaltrials.gov Identifier NCT01367743

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Objective To compare the clinical characteristics and outcomes of patients with acute heart failure (AHF) according to clinical profiles based on congestion and perfusion determined in the emergency department (ED). Methods and results Overall, 11 261 unselected AHF patients from 41 Spanish EDs were classified according to perfusion (normoperfusion = warm; hypoperfusion = cold) and congestion (not = dry; yes = wet). Baseline and decompensation characteristics were recorded as were the main wards to which patients were admitted. The primary outcome was 1‐year all‐cause mortality; secondary outcomes were need for hospitalisation during the index AHF event, in‐hospital all‐cause mortality, prolonged hospitalisation, 7‐day post‐discharge ED revisit for AHF and 30‐day post‐discharge rehospitalisation for AHF. A total of 8558 patients (76.0%) were warm + wet, 1929 (17.1%) cold + wet, 675 (6.0%) warm + dry, and 99 (0.9%) cold + dry; hypoperfused (cold) patients were more frequently admitted to intensive care units and geriatrics departments, and warm + wet patients were discharged home without admission. The four phenotypes differed in most of the baseline and decompensation characteristics. The 1‐year mortality was 30.8%, and compared to warm + dry, the adjusted hazard ratios were significantly increased for cold + wet (1.660; 95% confidence interval 1.400–1.968) and cold + dry (1.672; 95% confidence interval 1.189–2.351). Hypoperfused (cold) phenotypes also showed higher rates of index episode hospitalisation and in‐hospital mortality, while congestive (wet) phenotypes had a higher risk of prolonged hospitalisation but decreased risk of rehospitalisation. No differences were observed among phenotypes in ED revisit risk. Conclusions Bedside clinical evaluation of congestion and perfusion of AHF patients upon ED arrival and classification according to phenotypic profiles proposed by the latest European Society of Cardiology guidelines provide useful complementary information and help to rapidly predict patient outcomes shortly after ED patient arrival.

Aims Patients admitted for acute heart failure (HF) are at high risk of readmission and death, especially in the 90 days following discharge. We aimed to assess the safety and efficacy of early optimization of oral HF therapy with beta‐blockers (BB), angiotensin‐converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) or angiotensin receptor–neprilysin inhibitors (ARNi), and mineralocorticoid receptor antagonists (MRA) on 90‐day clinical outcomes in patients admitted for acute HF. Methods In a multicentre, randomized, open‐label, parallel‐group study, a total of 900 patients will be randomized in a 1:1 ratio to either ‘usual care’ or ‘high‐intensity care’. Patients enrolled in the usual care arm will be discharged and managed according to usual clinical practice at the site. In the high‐intensity care arm, doses of oral HF medications – including a BB, ACEi or ARB, and MRA – will be up‐titrated to 50% of recommended doses before discharge and to 100% of recommended doses within 2 weeks of discharge. Up‐titration will be delayed if the patients develop worsening symptoms and signs of congestion, hyperkalaemia, hypotension, bradycardia, worsening of renal function or significant increase in N‐terminal pro‐B‐type natriuretic peptide between visits. The primary endpoint is 90‐day all‐cause mortality or HF readmission. Conclusions STRONG‐HF is the first study to assess whether rapid up‐titration of evidence‐based guideline‐recommended therapies with close follow‐up in a large cohort of patients discharged from an acute HF admission is safe and can affect adverse outcomes during the first 90 days after discharge. Clinical Trial Registration: http://ClinicalTrials.gov Identifier NCT03412201.

The mechanism of radiation-induced dysfunction in rat submandibular glands was investigated at the cellular level. After X irradiation (single dose, 15 Gy), a vacuolation in the acinar cells or an enlargement of the acinar lumen was observed as a typical morphological change for 2 weeks. As observed using a video-enhanced contrast differential interference contrast (VEC-DIC) microscope, exocytosis and shrinkage of the acinar cells induced by application of pilocarpine (100 microM) were markedly suppressed for 5 days and then recovered to 80% of the control levels. Using an immunohistochemical method, no significant change was observed in amylase distribution, but a marked loss of aquaporin 5 was found in the acinar cells after the irradiation. The extent and time course of pilocarpine-induced mobilization of intracellular Ca(2+) did not change after the irradiation. We conclude that radiation-induced dysfunction in the salivary glands is due to an impairment of exocytosis and a reduction of water secretion. The loss of aquaporin 5 and possibly other membrane-fusion proteins in acinar cells may be the major mechanism underlying such a dysfunction.

Over the last 30 years, many medicine development programmes in acute and chronic heart failure (HF) with preserved ejection fraction (HFpEF) have failed, in contrast to those in HF with reduced ejection fraction (HFrEF). We explore how the neutral results in larger HF trials may be attributable to chance and/or the dilution of statistical power.