Long-term outcome in early survivors of cardiogenic shock at the acute stage of myocardial infarction: a landmark analysis from the French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) Registry

Despite considerable progress in the management of patients admitted for acute myocardial infarction (AMI), cardiogenic shock (CS) remains a major complication [1],[2]. In-hospital mortality has declined due to early revascularization and improved overall management, however, early mortality rates remain high; only about 50% of AMI patients developing CS are alive at one month [1]-[4].

Little data exist on the long-term outcomes of patients surviving the acute phase of CS following AMI [4]-[6]. Most studies report that patients with CS have an increased risk of death up to one year after the acute event. Beyond 1 year, mortality seems to be similar to that of patients without CS. However, most of these studies were performed in the 1990s., Marked reductions in AMI mortality have recently been reported, including among patients with CS [4]-[6].

The French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST MI) 2005 registry is a prospective, nationwide, observational study conducted at the end of 2005 in a large number of the French hospitals treating AMI patients [7],[8]. It allows evaluation of the long-term outcome in acute ST-elevation and non-ST-elevation myocardial infarction patients with and without CS. The aim of the present study was to analyse long-term outcomes of early survivors of the acute phase, according to the presence of CS at the acute stage.

The main finding of the present study in a contemporary real-world population of AMI patients, is that early survivors of CS still have higher mortality at 1 year, compared with early survivors without CS. Beyond 1 year, however, mortality up to 5 years becomes comparable between patients with or without CS at the acute stage, although the former have a more severe clinical profile. Mortality is higher in STEMI patients with CS than in NSTEMI patients with CS, and early revascularization is associated with better long-term survival.

Most data available on the long-term outcome of CS patients surviving the early phase of AMI were obtained before major changes in AMI treatment were widely implemented [3]-[5]. They are derived from populations selected for inclusion into randomized trials, or less frequently from real-life populations. Patient inclusion was usually before the year 2000, at a time when outcomes were notably poorer than nowadays [12].

Despite improved early management, early mortality in CS patients remains considerably higher than that of patients without CS [2],[13]. In prior studies the reported overall long-term survival of CS patients surviving the early period varies widely from 12% to 73% at 5 years [4]-[6],[14],[15]. In the large GUSTO-1 population of STEMI patients [5], mortality at 11 years in early survivors was 45% in patients with CS, compared with 31% in patients without CS. Patients included in the trial were relatively young and had to fulfill the trial inclusion criteria, which included early presentation after symptom onset, and all received intravenous fibrinolytic therapy. Our patients were enrolled in 2005, and more than 80% of patients underwent myocardial revascularization. This clearly differentiates our study, which is therefore clinically relevant in the current era.

To the best of our knowledge, there has been only one recent report on a large contemporary series of patients with long-term follow up after CS [16]. The data, gathered from the CRUSADE registry cross-linked with the Medicare administrative database, were limited to older (≥65 years) patients and only included NSTEMI patients. Four-year survival in CS early survivors was 48%, compared with 56.5% in non-CS survivors. Another novelty of our study is that both STEMI and NSTEMI patients were included.

In this population, 5-year survival of CS patients alive after the acute phase was 59%. Improvements in primary angioplasty and adjunctive pharmacotherapy are likely to explain higher survival rates [4],[5] in recent series. Of note, a majority of our patients had undergone myocardial revascularization during the initial hospital stay and early revascularization was associated with better long-term survival. In the SHOCK trial, early revascularization significantly reduced 6-year mortality in early survivors by 41% (absolute risk reduction: 18%) [4]. Our study underlines the potential interest of performing immediate coronary reperfusion in CS, as it is also associated with improved long-term survival. In this regard, developing networks for the management of AMI patients, particularly for the most severely affected patients, seems important to improve both early and long-term outcomes.

A consistent finding in all studies, including ours, is similar mortality beyond 1 year in patients with or without CS, regardless of the period studied or the inclusion of STEMI or NSTEMI patients. The GUSTO-1 study confirmed similar long-term survival between CS and non-CS patients who were alive at 1 year. In the much more recent CRUSADE registry in NSTEMI patients 65 years of age or older, no difference was observed between patients with or without CS, once they had survived the first months following the acute episode [16]. The reasons for late survival becoming similar are unclear, especially when considering the difference in LVEF between patients who have developed CS and those who have not. Mechanisms leading to CS include left ventricular dysfunction, systemic inflammatory response, activation of complement, release of cytokines, and expression of inducible nitric oxide synthase [4],[14],[17]. The recent IABP SHOCK II trial confirmed the presence of a high degree of inflammatory response in CS patients, irrespective of the management strategy, and that CS could be present even in the absence of profound LV dysfunction (median LVEF 35%) [17]. The resolution of severe ischaemia and/or neurohormonal abnormalities may explain the potential reversibility of shock [4],[14]. Also, the increasing use of medications such as beta-blockers, ACE-inhibitors, ARBs or aldosterone blockers in patients with CS during the hospital admission may have participated in their improved long-term survival; of note, the percentage of patients with CS receiving beta-blockers increased from 68% at discharge to 81% at one year, and the percentage of patients receiving either ACE-inhibitors or ARBs marginally increased from 78% to 81% .

The long-term outcome for early survivors of CS is worse than that of patients without CS. Patients who survive the first year after the acute event, however, have a 5-year survival rate similar to that of non-CS patients. This divergence between early, semi-early, and long-term outcomes has remained consistent since the late 1980s and underlines the importance of improving short-term outcome by the early detection and management of CS, including early myocardial revascularisation.

Early survivors of CS still have a higher mortality at 1 year, compared with early survivors without CS

Beyond 1 year, however, mortality up to 5 years becomes comparable between patients with or without CS at the acute stage, although the former have a more severe initial profile

Mortality is higher in STEMI patients with CS than in NSTEMI patients with CS

Early revascularization is associated with better long-term survival in CS patients following acute myocardial infarction

NA conceived the study, drafted the manuscript, wrote the manuscript and revised the manuscript. EP helped to draft the manuscript and perform statistical analysis and helped to revise the manuscript. TS helped in acquisition of data, drafting the manuscript and statistical analysis. EBC helped in acquisition of data, and helped to conceive the study and correct the manuscript. DA helped in acquisition of data, interpretation of data and correction of the manuscript. FS participated in the design of the study, performed the statistical analysis and helped to revise the manuscript. HB helped in acquisition of data, interpretation of data, and drafting and revising the manuscript. PQ helped in acquisition of data, drafting the manuscript and performing the revision. FP helped in acquisition of data, drafting the manuscript and statistical analysis. ED helped in acquisition of data and revised it critically for important intellectual content. LB helped in acquisition of data, drafting the manuscript and statistical analysis. DB helped in acquisition and interpretation of data and revised it critically for important intellectual content. ND conceived of the study, performed the statistical analysis and the interpretation of data, and corrected the manuscript. All authors read the manuscript and gave final approval of the version to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.