The terms CPAP and NPPV are sometimes used interchangeably, but they are different. With noninvasive CPAP, an interface (usually a face mask) is used to apply a pressure greater than atmospheric to the proximal airway throughout spontaneous breathing, thus splinting open the upper airway, increasing lung volume and intra-thoracic pressure. The work of breathing is entirely assumed by the patient and the tidal ventilation is completely dependent on the respiratory muscles. NPPV differs from CPAP because it has two pressure levels, an inspiratory positive airway pressure (which provides mechanical breaths) and an expiratory positive airway pressure, acting as positive end-expiratory pressure (PEEP).

Acute cardiogenic pulmonary edema is characterized by an increase in left ventricle filling pressures, causing a rise in pulmonary capillary pressure, and thereafter fluid overload toward the pulmonary interstitial compartment and alveolar spaces [12]. All these factors lead to an increase in airway resistance, a decrease in lung diffusion capacity, a drop in functional residual capacity, and an increased intrapulmonary shunt effect. Hypoxemia develops, associated with an increase in respiratory effort.

The application of intrathoracic positive pressure in patients with ACPE, particularly with PEEP, has the following cardiovascular effects: (a) a decrease in venous return and in right ventricle preload; (b) a decrease in transmural pressure (transmural pressure = intraventricular pressure − intrathoracic pressure); and (c) a reduction in left ventricle afterload [13–15]. Cardiac output and myocardial contractility may increase. Moreover, the application of positive pressure produces also respiratory effects. In particular, it favors alveolar recruitment and increases functional residual capacity, lung compliance, and alveolar ventilation, with a reduction of the intrapulmonary shunt and respiratory effort, thus improving oxygenation [16].

Compared with conventional oxygen therapy, the application of NIV (both CPAP and NPPV) [17–20] was associated with faster clinical (reduction of respiratory frequency and of dyspneic sensation) and blood gas improvements (increased PaO₂, reduction of PaCO₂ and acidosis) [21]. NPPV has the potential advantage over CPAP of assisting the respiratory muscles during inspiration, resulting in faster alleviation of dyspnea [22–24].

In a retrospective observational study in consecutive patients admitted for ACPE, neither acidemia nor the type of acidosis on admission was a risk factor for adverse outcome in ACPE patients treated with CPAP [25]. Similar results were reported by our group [26] in 65 consecutive patients with ACPE treated with NIV, characterized by a more severe hemodynamic impairment as inferred by the high percentage of devices used and administration of inotropes.

CPAP was reported to improve survival and avoid intubation in ACPE patients compared with conventional treatment plus oxygen therapy [8, 27–35], and five systematic reviews [6–8, 31, 36] consistently demonstrated a significant reduction in endotracheal intubation with both types of NIV.

The 3CPO trial (Three Interventions in Cardiogenic Pulmonary Oedema), a large randomized controlled trial including 1069 patients, showed no difference in short- or long-term mortality rates between standard oxygen therapy and NIV treatments in patients presenting to emergency departments with severe ACPE [21]. This finding was not confirmed in a subsequent meta-analysis [9] (including the 3CPO and five meta-analyses) [6, 8, 33, 37], which reported a significant mortality benefit of NPPV in ACPE (fixed effect model, risk ratio 0.75, CI 0.61–0.92).

In a Cochrane review [38], including 21 studies and 1,071 subjects, NIV, compared with standard care, significantly reduced the need for endotracheal intubation, with a RR of 0.53 (95 % CI 0.34–0.83) and a NNT (number needed to treat) of 8. There was also a significant reduction in hospital mortality (RR 0.6, 95 % CI 0.45–0.84) and a NNT of 13. Similar results were reported by Winck et al. [31], in their meta-analysis, which showed that, in ACPE patients, CPAP and NPPV both significantly decrease the need for endotracheal intubation, and CPAP significantly reduces mortality when compared with standard medical therapy. A reduction in mortality was also reported by Mariani et al. [27], with NIV delivered through either NPPV or CPAP in ACPE patients.

A recent meta-analysis [39] (including 78 randomized controlled trials) was specifically focused on the effect of NIV on mortality in acute care settings. In the sub-analysis of patients with ACPE, NIV showed a beneficial effect on survival when applied to treat acute respiratory failure (RR 0.64, 95 % CI 0.45–0.90, p = 0.01, NNT = 16). However, in trials allowing crossover, with NIV used a rescue therapy, this benefit was not confirmed. This finding strongly suggests the need to focus future research on the best timing for NIV treatment in ACPE.

Inclusion and exclusion criteria varied among the trials. All 15 trials from 2000 to 2009 excluded patients with cardiogenic shock. In addition, 9 of these 15 trials, and 8 of the 10 trials in the period 2005–2009, also excluded patients who required acute coronary revascularization [19–22, 40–42], or who had acute coronary syndrome [43, 44].

An early RCT suggested that NPPV was associated with a greater risk of myocardial infarction than was CPAP [45], but many subsequent RCTs did not confirm this finding [8, 15, 22, 38, 41, 43, 44]. In the Cochrane review by Vital et al. [38], NIV was not associated with an increased risk in the incidence of myocardial infarction (RR 1.24, 95 % CI 0.79–1.95) when compared with standard medical care. In the meta-analysis by Weng et al. [28], NIV was not associated with an incidence of new myocardial infarction and, likewise, in the meta-analysis of Li H et al. [46], which included 12 RCTs with a total of 1,433 ACPE patients, the occurrence of new cases of myocardial infarction and length of stay were also not significantly different between CPAP and NPPV.

According to the available evidence, NIV can be safely used in patients with acute coronary syndrome (ACS) complicated by acute respiratory failure due to ACPE. In clinical practice, the use of NIV in these patients seems to still be related to local practices. In the FINN AKVA study group, including 620 acute heart failure (AHF) patients [47], NIV was used more frequently in the ACS-AHF than in the non-ACS-AHF patients (38 % vs 18 %, respectively, p < 0.001) [48], but only half of patients with cardiogenic shock and pulmonary edema were treated with NIV [47].