Residual SYNTAX Score After Revascularization in Cardiogenic Shock

Acute myocardial infarction–related cardiogenic shock (AMI-CS) continues to have a very high mortality rate, at 40% to 50%; randomized data demonstrate that early revascularization is the only proven beneficial therapy (1). Coronary revascularization encompasses a heterogeneous group of treatments, especially for multivessel coronary artery disease (CAD). Multivessel CAD is very common in AMI-CS, occurring in around 75% of cases (2). The extent of CAD can be measured by the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (SS). The SS is an angiographic grading tool that quantifies CAD based on lesion number, location, and complexity (3). The residual SYNTAX score (rSS) can be calculated following an initial revascularization approach. In AMI patients, high rSS scores are independently associated with mortality (4–6). However, most studies evaluating rSS excluded patients with AMI-CS; the prognostic significance of rSS in the setting of AMI-CS is unknown. In this issue of the Journal, Barthélémy et al. (7) performed a subanalysis of the CULPRIT-SHOCK (Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock) trial to assess the extent of CAD after revascularization using the rSS in AMI-CS patients. Additionally, they ascertained the prognostic utility of rSS for short- and long-term mortality.

The CULPRIT SHOCK trial randomized AMI-CS patients to culprit lesion–only percutaneous coronary intervention (CLO-PCI) versus immediate multivessel PCI (MV-PCI) (8). When compared with MV-PCI, CLO-PCI resulted in a lower rate of the composite endpoint of 30-day mortality and renal failure. A strength of this current analysis is rSS was measured by an angiographic core laboratory by 2 blinded investigators. There was a high degree of inter- and intraobserver reliability in rSS assessment. The median baseline SYNTAX score (bSS) was in the intermediate range (24.5), and the median rSS was in the low range (9.0). Complete revascularization (CR) (rSS = 0) was achieved in less than one-fifth of the study population (25% in MV-PCI vs. 9% in CLO-PCI). Regardless of revascularization strategy, higher rSS was independently associated with substantially increased risk of all cause death both at 30 days (adjusted odds ratio: 1.49) and at 1 year (adjusted odds ratio: 1.52).

The findings of this study appear to contrast with the overall results of the CULPRIT-SHOCK trial, in which upfront MV-PCI led to worse outcomes compared with CLO-PCI. Alternatively, this analysis reveals that patients with lower rSS are at a lower risk for death events, suggesting that additional interventions to reduce rSS in AMI-CS may plausibly improve survival. Importantly, these findings were derived from a secondary analysis and therefore should be viewed as hypothesis-generating. There is likely unmeasured confounding contributing to the relationship between lower rSS and improved survival. Higher rSS could be a surrogate marker for a higher-risk cohort among AMI-CS patients. Patients with higher rSS were older and had numerically higher rates of diabetes, peripheral artery disease, and prior AMI. Moreover, patients with higher rSS had statistically higher bSS. Patients with an rSS of 0 had a median bSS of 17.3, whereas patients with an rSS >14 had a much higher median bSS of 32.5 (7). Mechanistically, this higher baseline burden of atherosclerotic vascular disease could contribute to mortality by promoting a larger ischemic territory, impairing myocardial recovery, and increasing the risk of vascular complications. Furthermore, this subanalysis may emphasize the importance of timing in treatment of nonculprit lesions. In the acute treatment of patients with AMI-CS, less may be more. In the acute state of shock, it is beneficial to revascularize the culprit lesion and perhaps critical to minimize procedure-related complications. Posthemodynamic stabilization, staged revascularization to reduce rSS may benefit patients. In the CULPRIT-SHOCK trial, one-half of the survivors of CLO-PCI ultimately underwent staged PCI of nonculprit stenoses.

This study demonstrated low rates of CR in AMI-CS patients, even in the MV-PCI arm. The median rSS in this study was 9.0, which is substantially higher than the score of 2 to 5.5 in the ACS population without shock (4–6). There are several potential reasons why rSS was higher in this analysis compared with analyses of nonshock populations. First, the CULPRIT-SHOCK trial included AMI-CS patients with multivessel CAD, and those with single-vessel disease were excluded. These patients had anatomically extensive and complex baseline CAD, with more than one-fifth having at least 1 chronic total occlusion (CTO). Patients with AMI-CS are hemodynamically unstable and often have acute noncardiac organ dysfunction, which may limit the ability to safely perform CR to further reduce rSS. Additionally, it is unclear how much of the rSS is due to diffuse CAD versus discrete lesions. Another coronary consideration is the distinction between anatomically versus physiologically significant lesions. If investigated by invasive physiology, some of the anatomically significant lesions noted on the rSS may not meet ischemic thresholds. Thus, further efforts to achieve CR may expose patients to increased risks with unclear benefits.

There are multiple potential approaches to reduce rSS in AMI-CS patients, whether these approaches result in improved outcomes is an important area of future and ongoing investigations. First, in the CULPRIT-SHOCK trial, at least 1 CTO was present in over one-fifth of patients. Immediate revascularization of the CTO was attempted in about one-half of patients in the multivessel arm, and success was attained in only about one-third of cases. Even under hemodynamically stable conditions, the average CTO recanalization rates are relatively low (9,10). For clinically appropriate CTO interventions, patients may benefit from a staged approach and potentially even a referral to higher-volume CTO centers. Second, there were relatively few patients (27% to 28%) managed with mechanical circulatory support (MCS). MCS can stabilize hemodynamics, facilitate ventricular unloading, and enable more complete revascularization (11,12). Yet, the routine use of intra-aortic balloon pump in AMI-CS was shown to be ineffective in reducing 30-day mortality, and the various MCS devices are associated with high rates of bleeding and vascular complications (13–15). In the setting of AMI-CS, additional randomized controlled trials are needed to evaluate whether MCS translates into clinical outcomes benefits (16–20). Finally, coronary artery bypass grafting CABG) is an intriguing method to achieve more complete CR in AMI-CS. Patients who underwent PCI versus CABG had similar outcomes in the SHOCK (SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK) trial (1,21). In the CULPRIT-SHOCK trial, only a single patient in the CLO-PCI group underwent staged CABG. Thus, it remains unknown if AMI-CS patients who undergo CABG have reduced rSS and whether CABG confers a survival benefit. To address this question, there is a planned randomized controlled trial evaluating PCI versus CABG in patients with AMI-CS (22).

This study by Barthélémy et al. (7) is the first large study investigating residual CAD after revascularization for AMI-CS. The key findings of this study reveal that rates of CR after AMI-CS are low and that higher rSS is associated with increased short- and long-term all-cause mortality. More studies are needed to investigate whether further reduction in rSS could lead to improved outcomes for patients with AMI-CS using various revascularization strategies.