Heart failure is the leading cause of death in patients with acute myocardial infarction (AMI), with an incidence of 14% to 36% in patients admitted to hospital for AMI. Heart failure occurs after myocardial infarction due to a complex interplay between macrovascular occlusion, microvascular dysfunction, myocardial repression and remodeling, inflammation, and neurohormonal activation. Treatment requires rapid identification and timely application of guideline-guided treatments to improve mortality and morbidity. Recently, a review published in Prog Cardiovasc Dis elaborated on the pathogenesis of heart failure after myocardial infarction, current strategies for preventing and treating heart failure attacks after myocardial infarction, and promising treatment strategies. This article will summarize the relevant content of heart failure treatment after myocardial infarction for the benefit of readers.
Treatment of heart failure after myocardial infarction
Fig.1 Treatment of heart failure after myocardial infarction
Table 1 Treatment strategies
1. Myocardial reperfusion
Rapid restoration of myocardial perfusion remains the mainstay of treatment for AMI. Myocardial perfusion reduces infarct size and improves overall ventricular function. Restoring arterial blood flow in the first few hours after AMI saves myocardium and theoretically reduces the incidence of heart failure after myocardial infarction.
The American College of Cardiology (ACC)/American Heart Association (AHA)/Society for Cardiovascular Imaging and Intervention (SCAI) has included it in its Category I recommendations:
➤ For patients with STEMI who have ischemic symptoms lasting < 12 hours, PCI should be performed to improve survival. (Level A evidence) ➤ For patients with STEMI who have failed reperfusion after thrombolytic therapy, salvage PCI should be performed on the infarcted artery to improve clinical outcomes. (Level C Evidence)
➤ Primary PCI should be performed in patients with STEMI and CS or acute severe heart failure, regardless of whether the onset of myocardial infarction is delayed. (Level B evidence)
2. Angiotensin-converting enzyme inhibitors (ACE inhibitors)
ACE inhibitors have a clear benefit in improving the prognosis of patients with AMI and can be used in patients with heart failure after AMI. ACE inhibitors play an important role in reducing myocardial fibrosis, poor left ventricular remodeling, and afterload after myocardial infarction.
The ACC/AHA management guidelines give a Class I recommendation for the use of ACE inhibitors in patients with AMI:
➤ ACE inhibitors should be given within 24 hours for all patients with STEMI ≤ 40% of anterior wall lesions, heart failure, or LVEF 40%, unless contraindicated. (Level A Evidence)
➤ ACE inhibitors should be started and continued indefinitely in patients with LVEF ≤40% and those with hypertension, diabetes, or stable CKD, unless contraindicated. (Level A Evidence)
3. Angiotensin receptor blockers (ARBs)
For patients who are intolerant of ACE inhibitors, ARBs can be used as an alternative to ACE inhibitors.
In the ACC/AHA guidelines for the management of acute myocardial infarction, the use of ARB in patients with AMI is recommended for category I:
➤ ARBs should be given to patients with STEMI who have an indication for an ACE inhibitor but cannot tolerate it. (Level B evidence)
➤ ARBs are recommended for patients with ACE inhibitor intolerance, heart failure < LVEF 40%, or myocardial infarction. (Level A Evidence)
4.醛固酮受体拮抗剂（MRA）
MRA improves outcomes in patients with AMI and heart failure after myocardial infarction. MRA may prevent undesirable left ventricular remodeling by preventing myocardial fibrosis and myocardial hypertrophy.
ACC/AHA guidelines recommend MRA for patients with AMI:
➤ MRA is recommended for patients with post-myocardial infarction heart failure without significant renal dysfunction or hyperkalemia who are being treated with therapeutic doses of ACE inhibitors and β-blockers and have LVEF ≤40%, diabetes, or heart failure.
5. β Blockers (BBs)
BB can directly intervene in the adverse reactions of the continuous sympathetic nervous system and indirectly inhibit the RAAS pathway, which has a good therapeutic effect on patients with AMI. In addition, at the cellular level, BB has been shown to reduce poor remodeling by inhibiting myocardial fibrosis. BB is associated with a reduction in mortality and morbidity in patients with AMI, however, the timing of initiation of BB treatment remains controversial.
ACC/AHA guidelines recommend BB for patients with AMI:
➤ Patients without any of the following symptoms should start oral BB therapy within 24 hours: (1) signs of heart failure, (2) evidence of low output status, (3) increased risk of CS, or (4) other contraindications to BB (eg, PR interval > 0.24 s, second- or third-degree heart block without pacemaker, active asthma, or airway reactive disease). (Level A evidence) ➤ For patients with non-ST-elevation myocardial infarction-acute coronary syndrome (NSTE-ACS), stable heart failure, and reduced systolic function, it is recommended to continue BB therapy with 1 of the 3 drugs that have been shown to reduce mortality in patients with HF: metoprolol succinate extended-release, carvedilol, or bisoprolol. (Level C evidence) ➤ Patients with contraindications to BB within the first 24 hours of NSTE-ACS should be reassessed to determine their eligibility for subsequent use. (Level C Evidence)
➤ All patients with STEMI who do not have contraindications to their use should continue to use BB during and after hospitalization. (Level B evidence)
6. Statins
Statins have anti-inflammatory and antiproliferative effects on atherosclerosis-associated cells. Wright et al. showed that early administration of statins (within 24 hours) after AMI reduced in-hospital mortality. In addition, early administration of statins was associated with a reduced risk of developing heart failure after myocardial infarction during the index hospital stay. The use of high-intensity statins after AMI reduces the risk of heart failure after myocardial infarction.
ACC/AHA guidelines recommend high-intensity statins in patients with AMI:
➤ All patients with STEMI without contraindications should start or continue high-intensity statin therapy. (Level B evidence)
7. Angiotensin receptor neprilysin inhibitor (ARNI)
ARNI has shown superior outcomes to ARB in patients with chronic HF, and guidelines recommend that ARNI be used preferentially in patients with LVEF-reduced heart failure (HFrEF).
8.钠-葡萄糖共转运蛋白2（SGLT2）抑制剂
SGLT2 inhibitors have been recommended as guideline-guided therapies for the treatment of heart failure and may improve outcomes in patients with AMI, with possible mechanisms including attenuation of reperfusion injury and neurohormone activation. In addition, SGLT2 inhibitors have been shown to enhance endothelial function, myocardial energy metabolism, and cardiac contractility.
The EMPACT-MI trial (empagliflozin) and the DAPA-MI trial (dapagliflozin) are ongoing and will provide further evidence on the benefit of SGLT2 inhibitors in patients with AMI.
9. Supersaturated Oxygen Therapy (SSO₂)
Post-AMI infarct size is a marker to assess future morbidity and mortality. Strategies aimed at reducing the size of infarction can prevent poor cardiac remodeling after myocardial infarction and the risk of future heart failure. Despite early revascularization, PCI may not be sufficient to restore effective coronary perfusion due to the presence of microvascular dysfunction.
SSO₂ is a promising treatment that has been shown to be beneficial in terms of infarct size reduction after STEMI. Based on the results of clinical trials, SSO₂ treatment reduced infarct size from 25% to 27% to 19% in patients with STEMI after successful PCI. Further randomised controlled trials of SSO₂ treatment are needed to adequately assess clinical outcomes in patients with STEMI.
Cardiogenic shock
CS is the leading cause of in-hospital mortality in patients with AMI. In patients with AMI, the incidence of CS is 5% to 15%. Patients with AMI-associated cardiogenic shock (AMI-CS) have a 30-day mortality rate of 40% and a one-year mortality rate of nearly 50%. AMI-CS can occur in patients with STEMI or NSTEMI, and early revascularization has been identified as the mainstay of treatment to improve mortality in patients with AMI-CS.
Category I recommendations for CS in the ACC/AHA guidelines:
➤ For patients with AMI-CS due to pump failure after STEMI, primary PCI or coronary artery bypass grafting (CABG) for revascularization is recommended, regardless of the delay in the onset of myocardial infarction. (Level B evidence)
➤ Early revascularization is recommended for patients with AMI-CS due to cardiac pump failure after NSTE-ACS. (Level B evidence)
Mechanical Cycle Support (MCS) device
The mortality rate in patients with AMI-CS is very high, and observational data suggest an increase in the use of MCS devices that provide hemodynamic support to patients with AMI-CS.
1.主动脉内球囊反搏（IABP）
IABP is a commonly used MCS device that increases coronary blood flow and decreases left ventricular afterload through aortic counterpulsation.
In the IABP-Shock II study, 600 patients with AMI-CS were randomly assigned to IABP and control. The results showed no difference in the primary outcome of 30-day all-cause mortality between the two groups. The CRISP-AMI trial (n = 337) in anterior STEMI patients without AMI-CS showed no difference in the primary outcome (reduction in infarct size measured by CMR at 3 to 5 days after PCI) between the IABP and control groups. In addition, there was no difference in all-cause mortality at six months between the two groups. However, the evidence does not support the routine use of IABP in patients with AMI-CS.
2.Impella
The left ventricular assist device Impella is a short-term, miniature axial flow pump that intervenes percutaneously into the femoral or axillary arteries and enters the left ventricular cavity through the aortic valve. The Impella axial flow pump continuously draws blood from the left ventricle and pumps it directly into the ascending aorta.
The IMPRESS Severe Shock trial, designed to compare the outcomes of IABP and Impella in patients with AMI-CS, showed a statistically significant change in cardiac index at 30 minutes in the Impella group compared with the IABP group (P = 0.02). As the primary outcome of 30-day mortality was not significantly different between the two groups, the improvement in cardiac index did not translate into clinical improvement.
3.静脉-动脉体外膜肺氧合（VA-ECMO）
VA-ECMO is a mechanical circulatory support system that provides complete cardiopulmonary hemodynamic support. Small feasibility trials have evaluated the role of VA-ECMO in patients with AMI-CS.
In the ECLS-SHOCK preliminary study, 42 patients with AMI-CS were randomly divided into VA-ECMO group and control group. No significant difference was shown between the two groups for the primary outcome (improvement in LVEF at 30 days). In addition, there was a numerical reduction in all-cause mortality at 1 year (19%) in the VA-ECMO group compared with the control group (38%), but did not reach a statistically significant difference.
The EUROSHOCK trial included 35 patients with AMI-CS who were randomly assigned to either the VA-ECMO group or the control group. The results showed that the 1-year all-cause mortality rate (51.8%) in the VA-ECMO group was improved compared with the control group (81.5%).
The ECLS-SHOCK trial included 420 patients with AMI-CS who were scheduled for early revascularization. Patients were randomly divided into extracorporeal life support (ECLS) + conventional drug therapy (ECLS group) and conventional drug treatment (control group). The results showed that the 30-day all-cause mortality was 47.8% in the ECLS group and 49.0% in the control group. In addition, there was no difference in the risk of future myocardial infarction and HF hospitalization between the two groups.
Despite further understanding of the pathophysiology of AMI-CS, patient mortality remains high. There is an unmet need to identify which patients would benefit from the timely introduction of MCS devices to improve clinical outcomes in this patient population.
epilogue
Heart failure after myocardial infarction is common, and mortality and morbidity are high. Aggressive modification of risk factors, timely identification, and early application of guideline-directed therapy can improve outcomes in this population. Early revascularization is the only treatment that has shown a survival benefit in patients with CS, and the routine use of MCS devices requires further evaluation to identify high-risk patients who would benefit from these devices.
参考文献1. Akhtar KH, Khan MS, Baron SJ, et al. The spectrum of post-myocardial infarction care: From acute ischemia to heart failure. Prog Cardiovasc Dis. 2024 Jan-Feb;82:15-25. doi: 10.1016/j.pcad.2024.01.017. Epub 2024 Jan 17. PMID: 38242191.
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