Acute coronary syndrome (ACS) with acute systolic heart failure (ASHF) is a common medical condition that may be present when the patient is admitted to the hospital or may develop during hospitalization. In patients with ACS, the degree of heart failure is closely related to mortality [1]. Clinically speaking, signs and symptoms related to systemic congestion such as accumulation of extracellular fluid (initiated by increased biventricular cardiac filling pressures) are primarily observed in ASHF [2, 3]. In patients with ASHF, adverse cellular and anatomic changes can occur, promoting disease progression and adverse clinical outcomes as a result of abnormal loading conditions and enhanced ventricular wall stress, which is associated with 90-day readmission rates and 1-year mortality (10–30%) [4, 5].

Initial treatment in most patients with ASHF involves non-invasive ventilation and intravenous diuretics, which are either administered alone (typically in Europe and Asia) or combined with short-acting vasodilators [6]. A large number of studies focused on the impact of non-invasive ventilation on the prognosis of patients with acute heart failure has yielded inconsistent results [7, 8, 9]. There is limited evidence that non-invasive ventilation improves short- and long-term outcomes in ACS patients with ASHF. Therefore, we conducted this study focusing on evaluating our experience with non-invasive ventilation (NIV) in ASHF patients.

The major findings of this study are as follows: (1) NIV significantly reduced cardiac death and hospitalization intubation rates as well as the length of hospital stay in ACS patients with ASHF as compared with the control group. (2) At 1-year follow-up, all-cause mortality and cardiac death rate were significantly lower in the NIV group than in the control group. (3) The Cox model showed that not using NIV was an independent risk factor for all-cause mortality in ACS patients with ASHF. These results suggest that NIV treatment has a positive effect on the prognosis of ACS patients with ASHF.

In ASHF, patients with acute cardiogenic pulmonary edema tend to experience significant respiratory failure. The use of NIV, which provides positive intrathoracic pressure through an interface, is effective in treating some moderate to severe respiratory failure cases [19]. It has been reported that NIV use is associated with a lower incidence of endotracheal intubation in ASHF patients with ischemic etiology [20]. Furthermore, Zhu et al. [21] also reported that, in patients undergoing cardiothoracic surgery, the use of NIV improved patient’s oxygenation and decreased the need for endotracheal intubation. In our study, we also found that NIV groups showed lower endotracheal intubation rates. In addition, we also observed a significant reduction in mortality in the NIV group, both in hospital and at 1-year follow-up. However, another study, which included patients with ischemic cardiomyopathy and chronic obstructive pulmonary disease, found that NIV did not significantly improve short-term outcomes in patients with AHF [20]. In our study, which found positive improvements with NIV, we only enrolled ACS patients with ASHF. Another study, by Tanaka et al. [22], supports our view by reporting that the vital signs and oxygenation was improved in pulmonary edema patients received NIV treatment, and the intubation rate was also decreases. Evidence suggests that NIV can help improve blood oxygen content and hemorheological status, as well as minimize plasma lipid peroxidation injury [23]. Furthermore, our study suggests that the NIV can not only improve oxygen saturation in ACS patients with ASHF but also improve their survival rate. A previous study also demonstrated that continuous positive airway pressure treatment significantly reduced cognitive defects associated with obstructive sleep apnea, which decreased the incidence of major adverse cardiac events [24]. The cognitive level of patients was not evaluated in the present study, which is a limitation of this study.

The second most common indication for NIV is acute cardiogenic pulmonary edema, secondary to ASHF [25]. In patients with cardiogenic pulmonary edema who received NIV treatment, CPAP can rapidly improve oxygenation by re-expanding flooded alveoli and increase functional residual capacity, thereby positioning the lung on its compliance curve in a more favorable way (Fig. 4), which results in a reduction in breathing difficulty and improved cardiac performance [26]. The latter may be achieved by raising pericardial pressure, lowering left ventricular transmural pressure (systolic wall stress), and subsequently reducing afterload [27]. In our study, the efficacy of NIV in rapidly improving dyspnea, vital signs, and metabolic balance was established in ACS patients with ASHF. NIV resulted in significant improvements in heart rate, mean 24-hour urine output, CRP, eGFR, and NT-proBNP.

Fig. 4.

Positive pressure ventilation and cardiogenic pulmonary edema.

ASHF is characterized by an increased heart rate, which determines the amount of oxygen consumed and energy burnt by the myocardium [28]. Increased heart rate modulates cardiac afterload, reduces diastolic perfusion time, and triggers ischemic events and arrhythmias. A higher heart rate is often observed in patients with ASHF, which can be a compensatory mechanism to improve cardiac output as a result of vasopressor amines or as a contributing factor to clinical deterioration. Therefore, the reduction of heart rate may be among the most effective ways to save energy in patients with cardiogenic shock and multiorgan failure [29]. In patients who are hospitalized for ASHF, inflammation is also common. CRP, an acute-phase reactant that can be used to evaluate systemic inflammation, represents a nonspecific marker of inflammation [30]. Interestingly, numerous previous studies have reported that elevated CRP levels in the hospital may correlate with poor prognosis in patients with ASHF [31]. In our research, the CRP levels at discharge of patients in the NIV group were lower than of those in the control group, indicating that NIV treatment may have improved the clinical prognosis to a certain extent.

Patients presenting with ASHF have been reported to be affected by adverse clinical outcomes such as the possibility of intubation, stroke, malignant arrhythmia, rehospitalization, and unexpected demise [32]. According to the current study, the risk of endotracheal intubation is reduced by nearly half with NIV in comparison with standard therapy, which is in line with the majority of previous studies investigating the benefits of NIV, verifying the success and appropriateness of our therapeutic intervention [8]. Meta-analysis and systematic reviews have found that patients with acute cardiogenic pulmonary edema who were treated immediately with noninvasive ventilation had a 47% reduction in mortality [33, 34]. A similar rate of cardiac mortality was reported in our study compared to that reported by registries for patients with acute heart failure (6.7% in the EuroHeart Failure Survey II and 4% in the Acute Decompensated Heart Failure National Registry [ADHERE]) [35, 36].

To our surprise, our data demonstrated significant improvements in haemodynamic parameters, diuresis, and biochemical indices in the treated subjects, without observed differences in echocardiographic parameters. There are two possible reasons for this result. Firstly, a larger number of patients died in the control group (30 vs. 7) and so were excluded from the group’s echocardiographic parameters as these were assessed at discharge. This maybe contribute to absence of significant differences in echocardiographic parameters between the two groups due to all survivors having improved characteristics. Secondly, cardiac ultrasound is used to evaluate structural changes and is less sensitive than hemodynamic changes [37]. The patients in this study, all of whom had post-ischemic heart failure, were in the necrotic and edematous phases of cardiac myocytes, and no fibrotic repair had occurred. Therefore, changes in ejection fraction as well as cardiac structure had not yet occurred.

Our study has some limitations. First, it was a single-center study, and treatment choices were made based on physician preference, introducing a natural bias. However, the staff at the department of cardiology were competent and experienced in terms of the use of NIV in patients with ASHF. Second, learning bias could not be avoided due to this study not being a randomized controlled trial. Third, some of the patients who participated in our study received beta-blockers and so it was impossible to draw firm conclusions about acute changes in heart rate from our group.

In patients with ASHF, improvement occurs more rapidly in dyspnea with better effect on heart rate and metabolic balance with NIV than with standard oxygen therapy, effectively reducing intubation rate, duration of hospital stays, and 1-year mortality. To validate these findings, further large randomized controlled trials involving larger numbers of patients will be required.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

CQ, QZ, XL, and RZ conceived and designed the experiments. CQ, QZ, WC, ZD, XL, and RZ performed the experiments. CQ, and QZ analyzed the data. XL and RZ wrote the manuscript. All authors contributed to the manuscript and approved the submitted version.

The research protocol was authorized by the local ethics committee of each institution and was carried out in accordance with the provisions of the Declaration of Helsinki (Approval number is SYDWGZR-2020-128). All patients provided written informed consent prior to participation in the trials.

We would like to thank the members of the Department of Cardiaology for their assistance in the preparation of this manuscript.

This work was supported by the Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, Heilongjiang Province, China [grant number KF201823 (to CQ)].

The authors declare no conflict of interest.