Acute heart failure (AHF) is a common but serious condition associated with high morbidity and mortality. Unfortunately, the number of patients presenting with AHF is increasing, and most of these patients present with acute decompensated heart failure (ADHF) or acute on chronic heart failure (HF). Following diuretic treatment, most patients are discharged, but there are some patients who show signs and symptoms of worsening HF, which can result in escalation of therapy. Dr Nap referred to a recent study that showed that the patients who fare the worst are those with ADHF and signs of hypoperfusion and congestion; these signs can determine prognosis and affect renal, hepatic and pulmonary function, resulting in a multisystem disorder.1
Dr Nap recapped the pathophysiology of ADHF, which includes reduced left ventricular (LV) function and activation of the sympathetic nervous and renin–angiotensin systems. This, in turn, triggers neurohumoral activation and has a detrimental effect on renal function, increasing central venous pressure and wedge pressures.2,3 This leads to ventricular remodelling and dilated ventricles, and Dr Nap presented the pressure–volume loops that illustrate this advanced stage of morbidity. As congestion prevails and other organs become involved, ADHF becomes a multisystem disorder. Cardiogenic shock (CS) represents an advanced state of morbidity along this pathophysiological pathway of end organ hypoperfusion caused by reduced cardiac output and blood pressure.4
Dr Nap proceeded with reference to the Society for Cardiovascular Angiography and Intervention (SCAI) SHOCK criteria for defining the stages of CS severity from A to E.5 Higher SCAI SHOCK stages are associated with higher risks of mortality. This clinical classification of CS can help guide therapy, indicate prognosis and determine the effect of intervention. Due to the tendency of patients to spiral down the stages of CS severity, there is a time limit for intervention, without which the patient may otherwise deteriorate, and there is then the risk that haemodynamic derangement will become a metabolic derangement.
Dr Nap provided an overview of the treatment recommendations and their classifications as per the 2021 European Society of Cardiology guidelines and the 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines.6,7 Intravenous inotropic support is recommended for patients in CS (class of recommendation [COR] 1/level of evidence [LOE] B-NR) to maintain systemic perfusion and preserve end organ performance. For COR 2a/LOE B-NR in patients in CS, temporary mechanical circulatory support (MCS) is reasonable when end organ failure cannot be maintained by pharmacological means to support cardiac function. Both US and EU guidelines (COR IIa, LOE C) recommend short-term MCS in patients with CS or as a bridge-to-recovery, bridge-to-decision or bridge-to-bridge, and further indications include treatment of the cause of CS or long-term MCS or transplantation.6,7 Dr Nap suggested it may be appropriate to start patients with CS on MCS rather than inotropes, but there has been no randomised control trial showing inotropes have a positive effect on survival. He referred to a study that found that primary circulatory support with an intra-aortic balloon pump showed a significant increased in improved organ perfusion assessed by venous oxygen saturation (SvO2), compared with inotropes in decompensated HF and low output.8
Dr Nap explained that this context led to the hypothesis that the UNLOAD-HF trial is going to test: primary introduction of Impella in patients with ADHF with evidence of perfusion (SCAI CS Stages B and C) will result in superior outcomes compared with patients treated with standard treatment with inotropes. The primary endpoints at 60 days will be: all-cause mortality; worsening HF (to SCAI Stages D or E); the need for mechanical ventilation; and other organ failure (e.g. intubation, renal transplant and rehospitalisation/urgent hospital visit). Key secondary endpoints at 48 hours will be pulmonary capillary wedge pressure (PCWP) + right atrial pressure <30 mmHg; PCWP –25 mmHg; and PCWP –5 mmHg.
The study is a prospective randomised controlled open-label multicentre two-arm trial. One arm is Impella ± standard therapy with inotropes (intervention arm); the other arm is treatment with inotropes alone (control). The study is a two-stage design: Stage 1 includes two groups of 77 patients and Stage 2 includes two groups of 228 patients. Intention-to-treat and protocol analyses will be performed.
Inclusion criteria are ADHF (non-acute coronary syndrome) and evidence of reduced LV ejection fraction <35%; persistent signs and symptoms of congestion and evidence of SCAI criteria for CS Stages B–C with the presence of any of the following: hypotension (SBP <90 mmHg or mean arterial pressure <60 mmHg or vasoactive agents to maintain normotension); oliguria (≤0.5 ml/kg/h, ≤720 ml/24 h); lactate >2.0 mmol/l; increase in creatinine ≥0.3 mg/dl during the first 24 hours or amino-l-transferase >200 U/l. All patients must be 18–75 years of age.
Exclusion criteria include acute coronary syndrome, haemodynamic parameters/biochemistry as defined for SCAI CS Stages D or E; bradycardia and atrioventricular blocks necessitating pacemaker implantation; contraindications for Impella CP; bleeding diathesis or known coagulopathy; and inability to provide informed consent. Patients will be randomised into one of the two arms (either Impella ± inotropes or inotropes alone) and all patients will receive a pulmonary artery catheter to monitor pressures. Following the trial, patients will be weaned and commenced on guideline-directed medical therapy.
Dr Nap summarised his presentation by confirming that ADHF is a serious condition with a high morbidity and mortality characterised by congestion, impaired cardiac output/cardiac index and high filling pressures. Unloading is an attractive treatment option in patients with HF-CS and the UNLOAD-HF trial aims to assess whether LV unloading reduces clinical events in ADHF SCAI shock Stages B–C compared with standard treatment with inotropes.