January 2017 at a Glance: Oncology, Diabetes and Antidiabetic Treatment, Pulmonary Hypertension

Cardiovascular toxicity is among the most frequent adverse effects of cancer treatment and it may lead to premature death in cancer survivors. Cardio-oncology is now a major topic. Medical cancer therapy and radiation therapy may cause or accelerate the development of all the major cardiovascular diseases, including coronary artery disease, valve disease, arrhythmias, hypertension, thromboembolism, stroke. Development of myocardial dysfunction and heart failure (HF) has a major role. We are therefore proud to share with the European Heart Journal the publication of the recent ESC position paper on cancer treatment and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines.1 All the different cardiovascular complications of cancer treatment are considered, including their mechanisms, diagnosis, prevention and treatment. Targher et al. describe the clinical characteristics and prognosis of the diabetic patients hospitalized for acute HF enrolled in the ESC-HFA HF Long-Term Registry.2 Among the 6926 hospitalized for acute HF, 3422 (49.4%) were diabetics. Diabetes was independently associated with increased in-hospital and one-year mortality. In addition, independently of the diabetic status, blood glucose levels measured at the time of admission were predictive of increased mortality and this relation was maintained after adjustment for other variables for in-hospital, but not post-discharge, mortality.2 Empagliflozin, an inhibitor of the sodium-glucose cotransporter 2, has had favourable effects on HF events and mortality in a randomised, controlled, multicentre trial in diabetics at high cardiovascular risk.3 Consistently, the recent ESC guidelines state that it should be administered to delay the onset of HF in type 2 diabetic patients.4 We are proud to host in our journal a comprehensive review of the effects of antidiabetic drugs on the clinical course of HF.5 All the different glucose-lowering agents are considered and their effects on HF clinical course are shown and compared.5 This review can be a reference for clinical practice and future research. Glucagon-like peptide-1 analogues are another class of antidiabetic drugs that can improve cardiovascular outcomes in diabetic patients. These effects seem, however, independent of HF progression.5 We report in this issue the results of LIVE, an investigator-driven, double-blinded, multicentre placebo controlled trial of liraglutide versus placebo in 241 patients with HF and reduced ejection fraction (HFrEF). Liraglutide did not cause significant changes from baseline at week 24 in left ventricular (LV) EF, primary endpoint of the study, and in LV volumes with a small reduction in left atrial volume and an improvement in parameters of LV diastolic function. Heart rate increased by 7 bpm and there were more adverse events with liraglutide versus placebo.6 The interaction of diabetes with cardiac resynchronization therapy (CRT) in the Echo-CRT trial was examined by Nägele et al.7 A significant treatment interaction was observed with an increased risk of events, deaths and HF hospitalizations, in the CRT-ON versus the CRT-OFF group, in the non-diabetic patients and no difference in the diabetics. The significance of this interaction was reduced at multivariable analysis and was mainly observed for HF hospitalizations.7 The diastolic pulmonary pressure gradient (DPG), calculated as the difference between the diastolic pulmonary artery pressure and the mean pulmonary artery wedge pressure (PAWP), is used as an index of combined post- and pre-capillary pulmonary hypertension. However, some recent studies did not show a prognostic value of DPG and this may be caused by the patients having negative DPG values.8 Nagy et al. hypothesised that negative DPG may be caused by large V-waves in the PAWP tracings, caused by mitral regurgitation.9 In their analysis of 316 patients who underwent right heart catheterization and echocardiography, 48% of the 256 patients with pulmonary artery hypertension had negative DPG values. Among them, those with normal to low pulmonary vascular resistance had a significant inverse correlation between V-wave amplitude and the DPG values showing the important role of mitral regurgitation. Patients with a negative DPG had a better two-year outcome than those with positive values.9 Biering-Sørensen et al. studied 85 patients with dyspnoea, LVEF >50% and no significant valve disease who underwent speckle-tracking echocardiography followed by right heart catheterization and cardiopulmonary exercise testing.10 Resting longitudinal strain was lower and circumferential was higher in the patients with exercise-induced increase in PAWP and their ratio was the best predictor of an exercise-induced increase in pulmonary venous pressures.10 These data show that early abnormalities of LV systolic function may contribute to, or cause, symptoms in patients with preserved LVEF. Bendopnea, e.g. dyspnoea when bending forward, has recently been described in patients with HF.11 It was present in 49% of the 250 patients with decompensated HF studied by Baeza-Trinidad et al.12 Patients with bendopnea were more symptomatic, with larger left atria, high pulmonary artery pressure and poorer outcomes.12 Liu et al. studied the effects of sildenafil in HF patients with preserved EF in a 12-week double-blind placebo-controlled trial.13 Sildenafil did not change measurements of cardiac structure and function at echocardiography, decreased exercise heart rate and systolic blood pressure, and did not change the ventilator response to exercise, which decreased on placebo.13 It has been hypothesised that sacubitril/valsartan may increase beta-amyloid deposits in the brain with an increased risk of cognitive impairment.14 An analysis from PARADIGM-HF shows the lack of this risk, at least for the follow-up duration, with no difference in the number of these episodes compared with enalapril and with other previous trials.15, 16