After establishing the diagnosis, both pharmacological and, if needed, non-pharmacological treatment should be initiated as soon as possible. Treatment approach is dependent on how the patient presents. For example: inadequate oxygenation, life-threatening arrhythmias, low blood pressure (<90 mmHg) or cardiogenic shock, acute coronary syndrome and acute mechanical causes all require different management strategies.
Despite improvements in treatment, acute heart failure continues to have high rates of morbidity and mortality. Seeking to address this, the European Society of Cardiology – Acute Cardiovascular Care Association recently called for greater interdisciplinary care. The recommendations highlight the fragmentation of care many patients experience as a consequence of the multiple specialities involved in their management. The recommendations stress that an integrated care plan, based on the hospital’s resources and experience, is essential to drive improved and consistent care. While the recommendations made the call for greater interdisciplinary care, it also highlighted a series of gaps that require improvement. These included the need for early diagnosis and treatment, identification of an appropriate disposition for the majority of patients who do not require treatment in the intensive care unit at presentation, improvement in the diagnosis of accompanying acute myocardial infarction, and better assessment of intravascular volume status, which many physicians continue to perform suboptimally (Mueller et al., 2017).
In addition to provision of timely and effective treatment through interdisciplinary care, the inclusion of comprehensive inpatient monitoring is essential to optimising the management of patients with acute heart failure. The Acute Heart Failure Committee of the Heart Failure Association of the European Society of Cardiology recently released a statement outlining a recommended approach to utilising monitoring tools to enable improved decision making (Figure 13). With physicians under pressure to reduce hospital length of stay while preventing subsequent hospital visits, morbidity and mortality, the use of improved monitoring techniques may help them to achieve these goals (Harjola et al., 2018).
Intravenous loop diuretics (e.g. furosemide) are the cornerstone of treatment of congestion in patients with acute heart failure and are recommended for all patients with signs or symptoms of fluid overload. A furosemide bolus dose of 20–40 mg is recommended (Felker et al., 2011; Harjola et al., 2017; Shah et al., 2017). Guidelines recommend that treatment should be initiated as soon as possible, and early treatment has been shown to improve patient outcomes (Ponikowski et al., 2016; Mueller et al., 2017). A prospective study of 1,291 acute heart failure patients revealed that the mean door-to-furosemide (i.e. time from arrival at the emergency department to receival of first dose of furosemide) in the centre was 90 minutes. However, patients who received early treatment (door-to-furosemide <60 minutes) had significantly lower in-hospital mortality than patients who did not receive early treatment (2.3% vs. 6.0%, p=0.002), and this remained significant in multivariate analysis (OR 0.39, 95% CI 0.20–0.76, p=0.006) (Matsue et al., 2017). However, not all patients respond equally to loop diuretics and treatment may need to be modified. Analysis of patient data from the NHLBI Heart Failure Network ROSE-AHF and CARRESS-HF trials revealed that patients with a reduced fluid output, weight loss and response to diuretics was associated with increased 6-day mortality. Interestingly, elevated baseline cystatin C, a biomarker for renal dysfunction, was associated with a reduced diuretic response and, therefore, patients with renal insufficiency require higher doses of loop diuretics to achieve therapeutic decongestion (Kiernan et al., 2018).
Table 2. Positive inotropes and/or vasopressors used to treat acute heart failure
Intravenous vasodilators (nitrates, nitroprusside) are also helpful in relieving symptoms in patients with a systolic blood pressure > 90 mmHg. Vasodilators are often used in acute heart failure for patients who are hypertensive or have pulmonary oedema (Shah et al., 2017). However, robust data on their effect on outcomes are limited (Wakai et al., 2013; Harjola et al., 2017).
Positive inotropic agents (dopamine, dobutamine, milrinone, levosimendan) "should be reserved for patients with a severe reduction in cardiac output resulting in compromised vital organ perfusion", according to the current European guidelines (Ponikowski et al., 2016; Harjola et al., 2017). It is further stated that levosimendan should be preferred over dobutamine to reverse the effect of beta-blockade (Mebazaa et al., 2009). Some of the pharmacological differences observed between levosimendan and other inotropic agents are believed to be a consequence of it acting as a calcium sensitiser, rather than a calcium mobiliser, meaning cardiomyocytes are not exposed to high levels of ionic calcium and the resulting increase in myocardial oxygen consumption (Alternberger et al. 2018). The recommended dose of levosimendan is an optional bolus of 12 μg/kg over 10 min, followed by a continuous infusion of 0.1 μg/kg/min, which can be decreased to 0.05 or increased to 0.2 μg/kg/min (Ponikowski et al., 2016).
A position paper from 35 European experts examined the role of levosimendan – aiming to compile the evidence behind it and its potential use in less established settings. They noted that levosimendan improved left ventricular diastolic function, attenuated cardiac remodelling, increased coronary blood flow, helped to improve ventriculo-arterial coupling (the relationship between the myocardial contractility and arterial afterload), and may have a protective effect on the myocardium against ischaemia as investigated in animal models and some clinical studies with a limited number of patients (Papp et al., 2012). Clinical trials demonstrated beneficial anti-inflammatory effects in heart failure patients. They suggested that more evidence was required, but from these physiological findings as well as other data demonstrating the impact on organ systems, the drug is expected to have beneficial effects on other conditions associated with acute heart failure (Farmakis et al., 2016). A meta-analysis examining the use of levosimendan in patients with acute right heart failure indicated that levosimendan has short-term efficacy, increasing ejection fraction and tricuspid annular plane systolic excursion while significantly reducing systemic pulmonary artery pressure and pulmonary vascular resistance (Qiu et al., 2017). Another meta-analysis in patients with acute decompensated heart failure showed that treatment with levosimendan reduced brain natriuretic peptide versus control groups (except dopamine) and improved LVEF and increased heart rate compared with before administration (Zhou et al., 2018). It is believed to confer these effects by increasing the sensitivity of cardiomyocyte troponin C fibres to ionic calcium and by acting on potassium-dependent ATP channels on cardiac mitochondria and vascular smooth muscle cells (Altenberger et al., 2018).
Another position paper by a panel of 34 European experts recommend the use of levosimendan in patients with acute heart failure and/or cardiogenic shock complicating acute coronary syndrome depending on the presence of congestion, levels of blood pressure and heart rate, and the extent of cardiac ischemia. Levosimendan can be used alone or in combination with other agents, but it requires continuous monitoring due to the risk of hypotension (Nieminen MS et al., 2016).
In patients with cardiogenic shock unresponsive to inotropic agents, an intravenous vasopressor (noradrenaline preferably, or dopamine) can be given (De Backer et al., 2010).
When vasopressors or inotropic agents are used, blood pressure and ECG should be closely monitored, as they may cause arrhythmias or ischaemia. Levosimendan has been used in cardiogenic shock whenever blood pressure is ensured by noradrenaline.
Mechanical circulatory support, extracorporeal oxygenation (ECMO), ultrafiltration, and renal replacement therapy may be useful in selected patients. Short-term mechanical support can be considered in patients with cardiogenic shock refractory to other treatments (Ponikowski et al., 2016).
Oxygen is commonly used in patients with dyspnoea, however, supplemental oxygen has been shown to cause a fall in cardiac output and increase systemic vascular resistance and cardiac filling pressures. Therefore, it should be reserved for patients who experience hypoxaemia. Instead, non-invasive positive pressure ventilation can reduce dyspnoea, heart rate, hypercapnia, and in-hospital mortality (Shah et al., 2017).
Ultrafiltration (UF) can remove excess salt and fluid even if patients are resistant to high doses of diuretics. However, clinical studies of its use have shown mixed results with recent trials suggesting that UF offers no advantages over adjustable diuretic treatment, but with an increased number of adverse events. ESC guidelines recommend UF be considered in patients who fail diuretic therapy (Shah et al., 2017). The Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF) study indicated that UF was no more efficacious than an aggressive, urine-output guided pharmacological protocol for decongestion (Bart et al., 2012). However, to address issues with patient drop-out and treatment cross-over, a per-protocol analysis of the CARRESS-HF study was performed including only patients who were randomised to UF and had UF output collected or who were randomised to pharmacological treatment and had urine but not UF output collected. In this patient population, UF was associated with significantly higher cumulative fluid loss (P=0.003), net fluid loss (P=0.001) and relative reduction in weight (P=0.02) compared to the pharmacological treatment arm. UF was also associated with higher serum creatinine and blood urea nitrogen by 72 hours, lower serum sodium by 48 hours and increased plasma renin activity by 96 hours. However, no differences were observed in 60-day outcomes (Grodin et al., 2018).
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