September 2021 at a glance: focus on biomarkers, sex differences and adherence to medical treatment.

Abstract

Biomarkers represent useful tools in the management of patients with heart failure (HF). 1-3 Antigen carbohydrate 125 (CA125) is a novel marker of congestion, inflammation and right-sided HF. It emerged as an affordable and widely available tool for tailoring HF therapies and prognostic stratification, since high serum levels are associated with an increased risk of death and HF hospitalization.4 The role of cardiac troponin in HF is well-established.5 In the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction (EMPEROR-Reduced), increasing levels of high-sensitivity cardiac troponin T (hs-cTnT) were associated with higher rates of comorbidities (i.e. diabetes and atrial fibrillation), more advanced New York Heart Association functional class, decreased renal function, higher concentrations of natriuretic peptides and worse clinical course. However, empagliflozin reduced the primary endpoint of cardiovascular death or HF hospitalization, regardless of baseline hs-cTnT levels,6 confirming the role of sodium–glucose co-transporter 2 (SGLT2) inhibitors as an essential treatment for patients with HF with reduced ejection fraction (HFrEF).7-9 Sex-based differences exist among patients with HF.10, 11 In the Effects of High-Dose versus Low-Dose Losartan on Clinical Outcomes in Patients with Heart Failure (HEAAL) trial, women appeared to respond similarly to low and high doses of losartan, whereas men had more benefits with high doses. However, women were older compared with men and more frequently presented severe symptoms and renal dysfunction.12 Sex differences were also investigated in the Patient-centered Care Transitions in Heart Failure: A Pragmatic Cluster Randomized (PACT-HF) study, enrolling 986 patients with the aim to test the effect of a patient-centred transitional care model. Such model improved discharge preparedness, transition quality, and the health-related quality of life both at 6 weeks and 6 months, with no differences between men and women. Women had a lower quality of life score at discharge, but experienced more benefits from treatment compared with men.13 Dietary interventions are related to HF incidence and outcome.14, 15 A meta-analysis, including 122 randomized controlled trials and 176 097 participants, summarized and confirmed the impact of nutritional and dietary interventions on HF-related outcomes. In particular, coenzyme Q10 was associated with lower all-cause mortality, whereas Mediterranean diet was related with a lower risk of developing HF.16 Ergoreflex is a cardiorespiratory reflex activated during physical effort. HF patients often develop skeletal myopathy,17 which is associated with increasing ergoreflex sensitivity and dyspnoea on effort. Exercise training represents a valuable strategy to reduce such sensitivity and increase exercise tolerance.18 Among the quality of life measures tested in the PARALLAX trial (a randomized controlled trial of sacubitril/valsartan vs. individualized medical therapy in heart failure with mildly reduced and preserved ejection fraction), the Short Form Health Survey-36 physical functioning score was the most closely correlated with 6-min walk test (6MWT). A modest correlation was found between 6MWT and Kansas City Cardiomyopathy Questionnaire clinical summary score. Many factors were associated with worse values in both quality of life and exercise capacity (i.e. female sex, higher body mass index, higher levels of N-terminal pro-B-type natriuretic peptide and coronary artery disease).19 Adherence to guideline-directed medical therapy (GDMT) improves outcome in patients with HFrEF.20, 21 However, GDMT remains suboptimal in a large proportion of patients.22 A recent multinational observational study confirmed strong patterns of GDMT low-titration in HF patients. Target dose of angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers, beta-blockers, and angiotensin receptor–neprilysin inhibitors, was achieved in 15%, 10%, 12%, and 30% of patients, respectively. An early discontinuation of therapy was frequently observed, with ACEi being the most withdrawn agent (55% at 12 months), followed by mineralocorticoid receptor antagonists (MRA) (40% at 12 months).23 Bhatt et al.24 evaluated the effects of both sacubitril/valsartan and enalapril on co-prescribed beta-blockers and MRA in the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HH) trial. Sacubitril/valsartan did not influence beta-blocker treatment nor MRA initiation, but led to fewer MRA discontinuation compared to enalapril. The coronavirus disease 2019 (COVID-19) pandemic represented a great burden for the HF community.25-30 Management of heart transplant recipients require even tighter precautionary measures in this historical era.31 In a prospective single centre cohort study, including heart transplant recipients, short-term immunogenicity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine has been evaluated. Only 15% of patients displayed the presence of anti-spike IgG antibodies after the first dose, and a total of 49% responded to the full two-dose vaccine schedule. Older age and anti-metabolite-based immunosuppression were associated with lower immunogenicity.32