AIILV: Acute Inferior Infarction of the Left Ventricle; CASH: Cardiogenic Shock; PCI: Percutaneous Coronary Intervention; RV: Right Ventricular; RVI: Right Ventricular Infarction

It is estimated that 30% of all acute inferior myocardial infarctions of the left ventricle (AIILV) is associated with right ventricular infarction (RVI) [1,2]. RVI is frequently caused by proximal occlusion of the dominant right coronary artery [3,4]. Hemodynamic consequences of RVI are asymptomatic right ventricular (RV) dysfunction, RV insufficiency with distended jugular veins together with maintained blood pressure. In most severe cases RVI is followed by a systemic hypotension and cardiogenic shock (CASH). RVI is commonly used term to indicate acute RV dysfunction caused by free wall motion abnormalities and/or dilation of right ventricle in the presence of ischaemic but viable myocardium [2-5]. The occurrence of the RVI during AIILV is associated with high in-hospital mortality and morbidity [6,7]. The treatment of these patients involves primarily early reperfusion. Reperfusion, either by thrombolysis or percutaneous coronary intervention (PCI) enhances the recovery of RV function and improves clinical outcome and survival [8-10].

Successful thrombolysis improves survival in patients with RVI, while the absence of reperfusion is associated with persistent dysfunction of the right ventricle and increased mortality [8-11]. Unsuccessful recanalization of the infarcted artery during fibrinolytic therapy occurs primarily in patients with proximal occlusion of the right coronary artery. Poor coronary delivery of fibrinolytic agents and restenosis may occur due to hypotension following such intervention. In contrast, the PCI has a higher success rate for recanalization of the occluded artery and has rapid beneficial effects on the global RV performance and clinical outcome [10,12].

There is a large number of models and scoring systems to assess the patient’s risk of mortality in patients suffering acute myocardial infarction of the left ventricle [13-15]. Although RVI significantly increases the risk of in-hospital mortality in patients with AIILV, limited information is available about predictors of in-hospital mortality in these patients. Therefore the aim of the present study was to determine pre-procedural and intra-procedural predictors of in-hospital mortality in patients with AIILV, accompanied by RVI, who were treated with percutaneous coronary intervention.

Data were collected retrospectively from patients treated at the Coronary Care Unit at the Clinical Center of Serbia in Belgrade. During the three year period, from beginning of 2007 until the end of 2009, a total of 237 patients with acute inferior infarction of the left ventricle accompanied with infarction of the right ventricle were treated with primary PCI. Ten patients died during hospitalization and 227 survived. For determination of predictors of in-hospital mortality, medical records of survivors and non-survivors were analysed.

AIILV accompanied by RVI was diagnosed when the following criteria were fulfilled: persistent discomfort in the chest that lasted ≥ 20 min with ST segment elevation ≥1 mm in at least two inferior leads and ST segment elevation ≥ 1 mm in the right precordial lead V4 (V4R), and confirmed by significantly increased concentration in cardiac enzymes. The ST-segment elevation in the V4R was used for diagnosis of the RV dysfunction due to its high sensitivity and specificity, and correlation with early mortality [16-18].

Following diagnosis of AIILV accompanied by RVI all patients were treated with double antiplatelet therapy (i.e. aspirin and clopidogrel) and were sent to the catheterization labaratory for PCI. In order to reduce time to PCI, we did not perform echocardiography prior to intervention. Similarly, the Swan-Gantz catheterization was only performed in few patients who were haemodinamically unstable. Due to a significant increase in time to PCI associated with Swan- Gantz catheterization, these haemodynamically unstable patients were excluded from analysis.

Cardiogenic shock was defined as systolic blood pressure less than 90 mmHg for more than 30 minutes, or a requirement for inotropic drugs to maintain systolic blood pressure ≥ 90 mmHg, after excluding other causes including hypovolemia and hemorrhage. Cardiogenic shock with clear lung fields (Killip class 1), and distended jugular veins was considered as a consequence of RV insufficiency.

Pre-procedural flow in the infarcted artery and procedural success was evaluated by a cardiologist who performed a PCI according to the TIMI flow grading system [16].

Statistical analysis

All statistical analyses were performed using the Statistical Package for Social Sciences, version 15.0 (SPSS Inc, Chicago, IL, USA). Data are presented as means and standard deviation for continuous variables and as frequencies and percentages for categorical variables. Categorical values were compared by χ² analysis. Association between ischemia time and in-hospital mortality was assessed with Mann-Whitney U Test. Relationships between each variable and in-hospital mortality rates were re-assessed by calculating the odds ratio.

Multiple logistic regression analysis was performed to identify independent variables associated with in-hospital mortality. Stepwise selection of the variable and estimation of significant probabilities were computed by means of the maximal likelihood ratio test. The variables were entered in the multivariate model when they were significantly related to mortality. Further logistic regression analysis was performed taking into account factors influencing mortality in patients without CASH. All statistical tests were two sided, with α=0.05.

Patients

Mean (SD) age of the patients was 59.5 (10.8) years and 67% of patients were men. Cardiogenic shock was present in 11% and three vessel disease in 25%. A history of previous myocardial infarction was present in 10% and previous PCI in 5%. Mean ischemia time was 268.5 (160.9) minutes and mean door to balloon time was 88.5 (37.0) minutes (Table 1). Overall in-hospital mortality was 4.2% (10 out of 237).

Table 1: Demographic, Clinical, and Angiographic Characteristics of Patient Population

Angiographic success and in-hospital mortality

TIMI grade 3 flow was achieved in 90% of all patients. In-hospital mortality was 5.6% in patients with post-procedural TIMI flow 3 compared with 50% in patients with post-procedural TIMI flow <3 (p <0.0001). In-hospital mortality was significantly lower among patients who started treatment within 90 minutes after admission (p=0.018), who were under 60 years old (p = 0.019), without history of angina (p=0.046), previous myocardial infarction (p=0.026) or PCI (p =0.022), without cardiogenic shock (p <0.0001), three vessel disease (p=0.007), with Killip class1 (p <0.0001), heart rate <100 bpm (p=0.007) and no distension of jugular veins (p=0.013). Using regression analysis, the following predictors of in-hospital mortality were identified: age (i.e. ≥60 years), previous myocardial infarction, previous PCI, heart rate ≥100 bpm, Killip class >1, distension of jugular veins, cardiogenic shock, longer ischemia time, door to balloon time >90 min, postprocedural TIMI flow <3, and three vessel disease (Table 2).

Table 2: Predictors of in-hospital mortality: univariate analysis

Independent predictors of in-hospital mortality were CASH (54.5% vs. 4.5% without CASH, p=0.002) and technical success (50% with TIMI flow <3 vs. 5.6% with TIMI flow 3, p=0.026) (Table 3).

Table 3: Predictors of in-hospital mortality: Multivariate logistic regression analysis

Independent predictors of in-hospital mortality in group of patients without CASH were previous PCI (p=0.021) and Killip class >1 (p=0.019) (Table 4).

Table 4: Predictors of in-hospital mortality: Multivariate logistic regression analysis (group of patients without cardiogenic shock)

This is the first study to assess predictors of in-hospital mortality in patients suffering acute myocardial infarction accompanied with right ventricular infarction and threated with percutaneous coronary intervention. The major findings suggest that the strongest predictors of in-hospital mortality are cardiogenic shock and TIMI flow<3 in the infarcted artery. In the group of patients without cardiogenic shock the major predictors of in-hospital mortality are previous PCI and Killip Class >1.

There are a large number of models and scoring systems to assess the patient’s risk of mortality in patients suffering acute myocardial infarction of the left ventricle [13-15]. Although RVI significantly increases the risk of in-hospital mortality in patients with AIILV, prognostic risk factors for such outcome are still poorly established. Gumina and co-workers evaluated the application of TIMI risk score in patients with RVI and found that the initial TIMI risk score had the capability to predict in-hospital morbidity and mortality and long-term mortality [19]. However, the inclusion criteria for this study have been questioned in the relation to high in-hospital mortality rate of 22% [20]. It has been suggested that in-hospital and long-term mortality correlated with the degree of RV insufficiency during RVI but not with the admission TIMI risk score [21].

When PCI was established for treatment of patients with left ventricular infarction with ST elevation, angiographic parameters were found to be independent predictors of in-hospital and long-term mortality. The data from a large German registry of PCI (ALKK), with approximately 5,000 patients from 80 hospitals, showed that the independent predictors of in-hospital mortality in patients with left ventricular infarction with ST elevation, who underwent the PCI, were CASH, age, post-procedural TIMI flow less than 3, three-vessel disease, anterior infarction, the year of inclusion and, the number of PCI procedures in each center (other observed parameters were left bundle branch block, ischemia time and door to balloon time) [22]. In another study with more than 1,700 patients who suffered left ventricular infarction and underwent PCI, six independent predictors of 30-day mortality were identified: Killip class, age, anterior infarction, ischemia time, post-procedural TIMI flow and three-vessel disease, but not door to balloon time [23]. In our study independent predictors of in-hospital mortality in patients with AIILV accompanied by RVI who underwent primary PCI were CASH and post-procedural TIMI flow <3. It should be emphasized that in our study the CASH was primarily due to RV insufficiency (out of five surviving patients with CASH, three were without left ventricular insufficiency (Killip-1), one had mild insufficiency (Killip-2) and one had moderate to severe left ventricular insufficiency (Killip-3). Among the non-survivors, out of six patients with CASH, four patients were classified as Killip-1, one was classified as Killip-2 and one was classified as Killip-3.

Ischemia time and door to balloon time

In our study we distinguished the two time-domain variables: 1) ischemia time i.e. the time from the beginning of chest discomfort to first balloon inflation, and 2) door to balloon time i.e. the time from admission to hospital to first balloon inflation. These times are important because their influence on in-hospital mortality has been debated. The two large showed that there was no significant increase in in-hospital mortality as time to PCI increases, if this time was within the 12 hours after symptom onset [22,24]. This was further supported by Shöming and associates who demonstrated the amount of rescued myocardium (i.e. Salvage index) depends on the time from symptom onset to the beginning of the fibrinolytic therapy [25]. In contrast, the time until the beginning of PCI is not a predictor of mortality if performed within 12 hours after the onset of symptoms [25]. In contrast, more recent study suggests that shorter time from the onset of symptoms to PCI was associated with smaller infarct size, less microvascular obstruction and larger amounts of rescued myocardium [26]. It is clear that the duration of ischemia time is inversely related to the size of myocardial infarciton. Indeed, it seems that duration of ischemia time can be critical in high risk patients with large ischemia as supported with correlation between ishemia time and in-hospital mortality in studies with high-risk patients [23,27,28]. In addition to strong relationship between door to balloon time and in-hospital mortality, evidence further suggests that there is increased risk for in-hospital mortality when this time is longer than 2 hours [24]. Interestingly, these results were not confirmed during large multi-centre trials [22,29]. This discrepancy is likely to be explained by different time interval between door to balloon which was 83 vs. 55 minutes [22,26,29]. It has further been suggested that an additional non-linear reduction in in-hospital mortality was associated with progressive reduction of door to balloon time below 90 minutes [30]. Current recommendation suggests that this time should be shorter than 90 minutes [31]. In our study, although the ischemia time and door to balloon time were risk factors for in-hospital mortality, their impact at multi-variate analysis was diminished by the strong influence of CASH, procedural failure on in-hospital mortality, left ventricular insufficiency, and previous PCI in patients without CASH.

The present study is not without limitations. The sample size is relatively small with only 10 mortality events, and therefore the study may have not sufficient power. Nevertheless we strongly believe that our findings are clinically relevant and will drive development of future large studies in this area.

In patients with acute infarction of the inferior wall of the left ventricle, which is considered to be low risk, when accompanied by right ventricular infarction, and treated with percutaneous coronary intervention within 12 hours after symptom onset, the independent predictors of in-hospital mortality are cardiogenic shock caused by right ventricular insufficiency and procedural failure of percutaneous coronary intervention confirmed by post-procedural TIMI flow <3 in the infarcted artery. In the group of patients without cardiogenic shock, the risk for in-hospital mortality is associated with the degree of left ventricular insufficiency during infarction and previous percutaneous coronary intervention. Future large clinical studies are required to enhance our understanding of mortality predictors in right ventricular infraction.

The authors declare no conflict of interests.

We are grateful to Dr Guy A MacGowan from Freeman Hospital, Newcastle uypon Tyne, UK for his critical review of the manuscript.