The mortality rate for cardiac arrest (CA) patients is still high even in the presence of initial resuscitation success.[1] CA patients frequently develop post-cardiac arrest syndrome (PCAS) immediately after the return of spontaneous circulation (ROSC), and PCAS is divided into four phases: Immediate phase (within 20 min), early phase (between 20 min and 6 to 12 h), intermediate phase (between 6 to 12 h and 72 h) and recovery phase (beyond 72 h). Interventions at the early to mid-term stages are closely associated with outcome.[2] In terms of pathophysiologic progress, PCAS comprises brain injury, a cause of mortality in two-thirds of out-of-hospital cardiac arrest (OHCA) patients,[3] myocardial dysfunction and circulatory shock, which are reversible phenomena, ischemia/reperfusion response, which occurs when spontaneous circulation is restored from the stop-page of normal blood flow in the event of CA[4] and persistent precipitating pathology.[5] According to a previous study, cardiovascular shock and brain injury are the leading causes of mortality in patients with ROSC after CA, and cardiovascular shock is the most common cause of death in the early stage of hospitalization.[6] Early arterial hypotension is also common after ROSC and is known as a predictor of mortality.[7] Skulec et al.[8] found a higher mortality rate in CA survivors who developed cardiogenic shock during therapeutic hypothermia, when compared with those who did not have the shock. Among the components of PCAS, myocardium dysfunction has been a phenomenon called ‘myocardial stunning and reported and studied in clinical research.[9] Myocardium dysfunction (MD) is defined as the reversible reduction of myocardial function despite normal or almost-normal blood flow with no non-reversible lesion, and MD may continue even after myocardial reperfusion.[10] MD is manifested primarily by a diffuse decrease in myocardial force of contraction, extended ischemia and wall thickening on the left ventricle, leading to an increase in end-diastolic volume.[11] The said components of PCAS increase the risk of developing hypotension and multiple organ dysfunction.[7,12] MD frequently occurs in cardiac arrest survivors but started to recover at 24 h post-CA and then recovered at 72 h.[13] Many studies reported that MD subsequently results in worsening clinical outcome. However, there have not been enough studies addressing the degree of deterioration and outcomes found. [10] Transthoracic echocardiography (TTE) is a bed-side real-time diagnostic tool used for post-ROSC patients, and the use of this tool in CA patients can be useful for prognostic judgement.[14,15]

The aim of this study was to investigate the impact of initial post-ROSC myocardial dysfunction on mortality and neurological outcome.

A total of 1,042 CA patients were admitted to our ED, and 263 of them were admitted to ICU after ROSC. Of those, 104 patients were included in this study, and the remaining patients were excluded because they did not undergo TTM or they were lost to follow-up (Fig. 1).

The patients’ mean age was 54.4 ± 15.3, and male patients accounted for 72.1% of total patients. The cause of CA was related to heart in 55 (52.9%) patients, the average time to BLS and ACLS was 8.7 ± 8.8 min and 24.0 ± 12.4 min, respectively. The average time from CA to ROSC was 28.0 ± 16.1 min. The initial heart rhythm, which is the most commonly identified after CA, was ventricular fibrillation/ventricular tachycardia (39.8%), followed by asystole (37.9%) and pulseless electrical activity (23.3%) As for medical history, 34.6% of patients had hypertension and 19.2% of patients had diabetes. According to TTE results, the largest number of patients had a LVEDD 42-54 mm (65.4%), a LVESD 24-36 mm (55.8%) and a LVEF > 55% (45.2%), respectively, in each respective group. At admission, coronary angioplasty (PTCA) was conducted in 19.2% of patients (Table 1).

During TTE evaluation, hemodynamics in patients showed systolic blood pressure 122.5 ± 30.0 mmHg. diastolic blood pressure 75.2 ± 18.8 mmHg and heart rate 85.2 ± 23.7 bpm. The mean time to completion of TTE was 16.7 ± 12.9 h. At the time of TTE, the mean temperature of patients was 34.3 ± 1.5℃, and regional wall motion abnormality (RWMA) was observed in 26.9% of patients.

Based on TTE findings, patients were divided into groups according to prognostic values for neurological outcome at 6 months, mortality at 3 months and mortality at 7 days. In analysis of neurological outcome, 36 patients had favorable CPC and 68 had unfavorable CPC. There were significant differences between favorable and unfavorable outcome groups with respect to initial rhythm during CA, time to ROSC, causes of CA, APACHE II score, blood lactic acid level, coronary angioplasty performed (p ≤ 0.001, < 0.001, < 0.001, 0.005, 0.021, 0.033). Ventricular fibrillation/ventricular tachycardia was most common, occurring in 65.7% of patients with favorable outcome, while asystole was the most common in the unfavorable outcome group (48.5%) The mean time to ROSC was 19.3 ± 11.5 min in the favorable outcome group and 32.6 ± 16.3 min in the unfavorable outcome group. With regard to survival at 3 months after CA, the patients who survived were 62 (59.6%), and those who died were 42 patients (40.4%). The most common initial rhythm was ventricular fibrillation/ventricular tachycardia in the survival group (47.5%) and asystole in the mortality group (57.1%) (p = 0.004). The mean time to ROSC was 23.0 ± 14.5 min in the survival group and 35.5 ± 15.5 min in the mortality group (p < 0.001). With regard to survival at 7 days, 79 (76.0%) patients survived and 25 (24.0%) died. Severe cardiac dysfunction occurred in 25 (31.7%) of patients survived and 14 (56.0%) of patients dead (p = 0.028) (Table 2).

Multivariate analysis was performed to identify variables that were statistically significant in univariate analysis. Taken together, two variables of time to ROSC and APACHE II scores were positively associated with mortality, and LVEF <45% were associated with increased mortality within 7 days after CA (odds ratio [OR] 1.04 [95% confidence interval (CI), 1.00-1.07], OR 1.10 [95% CI, 1.01-1.20], OR 3.02 [95%CI, 1.01-9.08]) (Table 3, Fig. 2).

In the present study, we identified the association between left ventricular function and short-term mortality in OHCA patients. Neurological outcome is one of the leading causes of death in OHCA patients with ROSC, and post-CA shock is another leading cause of death for them.[3,16] Post CA shock is characterized by ischemia/reperfusion injury of the brain or other organs after ROSC in CA survivors.[14]

Laver et al.[3] stated that brain injury was the most common cause of death in patients with ROSC after CA by citing the mortality rate of 66.7% in OHCA patients and 22.9% in in-hospital CA patients. In another study, Herlitz et al.[17] claimed brain injury alone was the leading cause of death in CA patients (45%), followed by injuries of heart and brain (40%) and heart injury (9%).

Among some studies that reviewed prognostic factors in post CA patients, Bro-Jeppesen et al.[18] identified the average arterial pressure as an predictor of 30-mortality in their retrospective randomized study of hemodialysis and vasoconstrictor in 920 OHCA patients who underwent TTM. They added that the mean arterial pressure of 65 mmHg or lower increased the mortality rate and that the proportion of LVEF < 30% was higher in patients with lower mean arterial pressure.[18] Also, Thomsen et al.[19] reported bradycardia as a favorable prognostic factor for 180-day survival and favorable outcome in 234 patients who received TTM after psychogenic OHCA with ROSC and that the mean LVEF was higher by nearly 5% in patients with bradycardia, compared with the group without bradycardia. They also assumed that slowed heart rate after TTM lengthens diastolic time and reduces oxygen consumption, allowing for maintenance of myocardial function and favorable outcome at the end.[20]

In CA patients, myocardial dysfunction represents a form of ischemia and reperfusion injury extensively occurred in CA patients after ROSC. MD is associated with mutual activation of underlying cardiac pathophysiology and myocardial injury during CA.[14] In their study investigating the association between MD and prognosis, Laurent et al.[21] reported that 73 (44.2%) of total 165 CA patients with ROSC were hemodynamically unstable in the early stage after admission (average 6.8 h), and 59 of them showed recovery from MD after 24 h. However, the remaining 12 unrecovered patients died from multiple organ failure in the early stage of admission.

According Palmer et al.[22], continued CPR has adverse impact on the left ventricle in a time dependent way at a later stage, and Xie et al.[23] also claimed the time-dependent adverse effects of defibrillation on the left ventricle. Separately, Chang et al.[14] suggested that LVEF level at 6 h after CA and isovolumic relaxation time are associated with patient survival rate.[15] In a study of cardiac index and neurological outcome, Torgersen et al.[24] reported a higher cardiac index in favorable neurological outcome group, compared with unfavorable neurological outcome group, suggesting the association between cardiac indexes and neurological outcome. In another study looking at the association between cardiac function and mortality, Fincke et al.[25] reported that cardiac output and the average arterial pressure were associated with increased mortality in patients with cardiogenic shock. In their study, LVEF was also investigated but this was not statistically significant.[25]

Thus many studies have investigated the mortality and prognosis in OHCA patients, but not many studies have been carried out concerning echocardiographic findings. Gonzalez et al.[26] looked at the results of TTE conducted before and after CA to determine the association between left ventricular systolic function and outcome in in-hospital CA patents and found that 49 (58.3%) of total 84 patients had a LVEF < 45% in TTE and that patients who had low left ventricular systolic function before CA demonstrated lower survival rate than patients with normal systolic function and showed further sever MD after CA. Ameloot et al.[27] reported the mean left ventricular cardiac output of 42% in 82 CA patients and 34% in patients with low venous oxygen saturation. The cardiac output of 42% is similar to that we found in the present study, in which sever MD occurred in 39 (37.5%) out of 104 OHCA patients with ROSC.

In summary, a variety of functional abnormalities occur immediately after ROSC in PCAS patients, and physicians should be attentive to MD to come up with treatment strategy. Severe MD, albeit temporary, can increase short-term mortality. In this study, MD was not significantly associated with 90-day mortality and neurological outcome, and this non-significant result is presumably due to the possibility that mortality rates in PCAS patients result from a combination of factors such as neurologic insult, in addition to myocardial dysfunction. Also, no significant association was found between LV dimensions and outcome in this study. This finding suggests that LV size may be affected by not only CA and CPR process but also pre-existing conditions before CA and that LV size itself may not be a good proxy for LV’s overall function.

This study has the following limitations: First, this is a retrospective study, and subjects were limited to patients treated at a single institution. However, by using CPR data that were systematically collected through the registry, we could minimize bias. Secondly, as several physicians, albeit trained in cardiology, read echocardiograms, differences in results cannot be ruled out. Thirdly, this study did not address the effects of inotropic agents and vasopressors, suggesting the need for further research. The limited number of patient cases can also pose a limitation.

Among components of PCAS, moderate or severe left ventricular dysfunction manifested by LVEF < 45% was found to be an independent prognostic factor for 7-day mortality although this component was not statistically related to 90-day mortality and neurological outcome. If LVEF is dropping in patients with PCAS, intravenous fluid and vasopressor can be therefore administered and mechanical intervention such as ECMO can be applied, if necessary. Further multicenter studies are needed to confirm these suggestions.