May 2021 at a glance: focus on acute heart failure and heart failure with preserved ejection fraction

Congestion is the main cause of hospitalization for acute heart failure (HF).1, 2 It can be detected by biomarkers and imaging tools for the diagnosis, prognostic evaluation and, possibly, to guide treatment, in patients with acute HF.3-7 Pellicori et al.8 reviewed ultrasound methods for the detection and quantification of congestion, including imaging of the heart, lungs (B-lines), kidneys (intrarenal venous flow) and venous system (inferior vena cava and internal jugular vein diameter). Organ injury may be a major mechanism of the deleterious effects of congestion in patients with acute HF.6 Kozhuharov et al.9 studied patients presenting to the emergency department with acute dyspnoea and showed that plasma levels of cardiac myosin-binding protein C (cMyC), a marker of myocardial injury, were higher in those with acute HF and were a marker of increased risk of all-cause mortality [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.66-2.89; P < 0.001 for patients above median cMyC concentrations]. Congestion relief has an impact on the prognostic value of markers of kidney function.6 In a prospective, single-centre study, 215 patients with acute HF were divided into four profiles based on their estimated glomerular filtration rate (eGFR) (preserved vs. impaired) and spot urine sodium (sodium excreter vs. non-excreter). Both sodium non-excreter profiles were associated with an increased risk of in-hospital worsening HF, use of inotropes and readmissions due to acute HF. The preserved eGFR/non-excreter profile had the highest 1-year mortality and was an independent predictor of poor outcome at multivariable aanalysis.10 Relief of congestion is the cornerstone of acute HF medical treatment.6, 11 In pre-clinical HF models, the novel dual acting vasopressin V1a/V2 receptor antagonist pecavaptan showed a better haemodynamic response compared to the V2 receptor selective antagonist tolvaptan.12 Sodium–glucose co-transporter 2 inhibitors have now a central role in HF treatment.13 The EMPULSE trial is a randomized, double-blind, parallel-group, placebo-controlled multinational trial to assess the effects of in-hospital initiation of empagliflozin in patients admitted for acute HF, regardless of diabetes history or left ventricular ejection fraction (LVEF).14 Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome.15 Many of these patients have impaired exercise capacity. Wolsk et al.16 analysed data from three previous studies, including 108 patients with HFpEF and 42 healthy controls who underwent exercise invasive haemodynamic assessment. Up to 56% of HFpEF patients showed chronotropic incompetence and had a smaller increase in stroke volume index during exercise compared with healthy subjects (4 ± 10 mL/m2 vs. 24 ± 12 mL/m2, P < 0.0001). Coronary microvascular dysfunction (CMD) is common in HFpEF patients but it has not been fully explored yet.17 Fifty-one patients with unexplained symptoms during effort, non-obstructive coronary artery disease and LVEF ≥50%, of whom 22 with HFpEF and 29 without HFpEF, underwent haemodynamic exercise assessment and concurrent coronary reactivity testing. At peak exercise, both endothelium-independent and endothelium-dependent CMD were associated with higher pulmonary capillary wedge pressure (PCWP). Only endothelium-independent CMD was associated with higher PCWP at rest and had a negative correlation with maximal exercise capacity.18 Serum potassium concentration has been largely associated with outcome in patients with HF and reduced ejection fraction but not in HFpEF.19, 20 In a post-hoc analysis of the PARAGON-HF [Prospective Comparison of ARNI (angiotensin receptor–neprilysin inhibitor) with ARB (angiotensin-receptor blockers) Global Outcomes in HFpEF) trial, hypo- and hyperkalaemia led to an increased risk of the composite endpoint of total HF hospitalizations or cardiovascular death, compared with normokalaemia (adjusted HR for hypokalaemia 1.55, 95% CI 1.30–1.85; P < 0.001, and for hyperkalaemia HR 1.21, 95% CI 1.02–1.44; P = 0.025). Hypokalaemia had the stronger association with all-cause and cardiovascular mortality, especially in patients with impaired kidney function.21 More than half of HFpEF patients present atrial fibrillation (AF).22, 23 Sugumar et al.24 studied 20 patients with HFpEF with exercise right heart catheterization after AF ablation. The patients remaining without AF had a significant reduction in peak exercise PCWP (29 ± 4 to 23 ± 2 mmHg, P < 0.01) and improvement in quality of life, compared with those with AF recurrence. Left atrial shunting represents an option for symptomatic HF patients with elevated PCWP. Results of the first-in-man study investigating the Atrial Flow Regulator for left atrial shunting in symptomatic HF patients (PRELIEVE study) are reported in this issue. Atrial Flow Regulator reduced rest PCWP at 3 months by 5 (−12, 0) mmHg (P = 0.0003, median Q1, Q3). No stroke, shunt occlusion, or new right HF was reported during the 1-year follow-up.25 Inhaled or intravenous sodium nitrite, as compared to placebo, was able to improve skeletal muscle oxygen conductance and oxygen delivery through an increase in cardiac output in patients with HFpEF.26 Nitric oxide deserves further investigation as a treatment to improve quality of life and exercise capacity of these patients.27