The study population included 1234 patients admitted with a diagnosis of STEMI between July 2009 and December 2014, either directly from the community to our center or transferred from one of its satellite hospitals, to perform emergent percutaneous coronary intervention. Of these, 26 patients were excluded as lost to follow-up (2%), and 50 patients (5%) presented with cardiogenic shock, defined as Killip class IV, on admission. Therefore, the study population consisted of 1158 patients without cardiogenic shock, presenting within 12hours of symptom onset and with persistent ST-segment elevation or new left bundle branch block, or>12hours after symptom onset and with ongoing ischemia, life-threatening arrhythmias or stuttering electrocardiogram (ECG) changes.

The diagnosis of STEMI was based on the presence of chest pain suggestive of myocardial ischemia, a 12-lead ECG showing persistent ST-segment elevation of≥2.5mm in men aged<40 years, >2mm in men aged≥40 years, and>1.5mm in women, in leads V2-V3 and/or>1mm in other leads (in the absence of left ventricular hypertrophy or left bundle branch block), or new left bundle branch block, and increased serum biomarkers of cardiac injury. The biomarkers used were cardiac troponin I and CK-MB, with a positive threshold of 0.06 and 3.5 ng/ml, respectively.

Heart failure was defined as Killip class≥2 during hospitalization.

Malignant arrhythmias were defined as ventricular fibrillation or sustained ventricular tachycardia.

Demographic, clinical, laboratory, echocardiographic and coronary angiographic data were collected prospectively and recorded in an electronic database (SIMACARDIO), in accordance with our department's protocol for patients admitted to the coronary care unit.

Regarding laboratory data, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured within 24hours of admission. Estimated glomerular filtration rate (eGFR) was obtained at presentation using the abbreviated Modification of Diet in Renal Disease (MDRD) formula. Anemia was defined according to the World Health Organization criteria (hemoglobin<12g/dl in women and<13g/dl in men).

Echocardiographic data were obtained from the first echocardiogram performed within 24hours of admission or as soon as a mechanical complication was suspected. Left ventricular systolic dysfunction was defined as left ventricular ejection fraction≤40%. Right ventricular systolic dysfunction was defined as tricuspid annular plane systolic excursion<16mm.

Significant coronary artery disease on coronary angiography was defined as≥50% stenosis of the left main artery or≥70% in other coronary arteries. Severe coronary disease was defined as left main disease and/or three-vessel disease. Coronary revascularization was defined as successful percutaneous or surgical coronary intervention in order to restore blood flow.

Preprocedural systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in the catheterization laboratory with the guide catheter placed in the ascending aorta. Heart rate was obtained at the same time from the corresponding ECG. MAP was calculated using the formula ((2×DBP)+SBP)/3. Preprocedural MSI was calculated using the formula heart rate/MAP.

The study's primary endpoint was six-month all-cause mortality and the secondary endpoint was the occurrence of cardiogenic shock during hospital stay.

Patients in this study were included in the National Registry of Acute Coronary Syndromes and were monitored for six months or until occurrence of the primary outcome. Follow-up was by phone calls and consultation of hospital records.

Receiver operating characteristic (ROC) curve analysis was used to determine the optimal threshold of MSI. Categorical variables were expressed as percentages and compared by the chi-square test or Fisher's exact test. Continuous variables were tested for normal distribution by the Kolmogorov-Smirnov test; all continuous variables had a normal distribution, and so between-group differences were compared using the t test and were expressed as means±standard deviation. Binary logistic regression analysis was performed to determine the independent predictors of occurrence of cardiogenic shock during hospital stay. Only four variables with statistical significance on univariate analysis were included, given the small numbers of events in the study. Cox proportional hazards regression analysis was used to determine independent predictors of six-month all-cause mortality, including only variables with statistical significance on univariate analysis. Kaplan-Meier survival curves were constructed to compare event-free survival at six months according to the threshold value obtained for MSI. The log rank test was used to test the equality of the survival function across groups. A two-sided p<0.05 was considered statistically significant. All statistical analyses were performed with SPSS software, version 21 (IBM SPSS Inc., Chicago, IL).

The mean age of the study population was 61.70±13.5 years; there was no significant age difference between the groups (Table 1).

The group with MSI≥0.93 had a higher proportion of women (21.9% vs. 16.5%; p=0.033) and patients with diabetes (28.4% vs. 21.6%; p=0.014). There were no statistically significant differences between groups regarding other conventional cardiovascular risk factors such as hypertension, dyslipidemia or smoking, or regarding previous cardiovascular history.

On admission, patients with MSI≥0.93 more frequently presented signs of acute heart failure (21.6% vs. 14%; p=0.002), anemia (29.2% vs. 17.8%; p<0.001) and renal insufficiency (eGFR<60ml/min/1.73 m2) (20.2% vs. 14.3%; p<0.001). On echocardiographic assessment, almost half of patients with MSI≥0.93 had left ventricular dysfunction (45.9% vs. 39.1%; p=0.045).

There were no statistical differences in terms of antithrombotic therapy, but patients with MSI≥0.93 were less often treated with beta-blockers (84% vs. 90%; p=0.004), angiotensin-converting enzyme (ACE) inhibitors (83% vs. 90%; p=0.001) and nitrates (14.2% vs. 19.5%, p=0.037) (Table 2). On the other hand, they more often required inotropic support (12.4% vs. 4.1%; p<0.001), levosimendan (2.8% vs. 0.4%; p=0.002) and diuretics (40.1% vs. 29.2%; p=0.002) (Table 2).

Total ischemic time and first medical contact-to-balloon time were not statistically different between groups. Regarding revascularization, there were no significant differences between groups, but patients with MSI≥0.93 more frequently required glycoprotein IIb/IIIa inhibitors (24% vs. 18.3%; p=0.015) due to evidence of massive thrombus during the angiographic procedure and no-reflow or slow flow situations.

Intra-aortic balloon pump support (7.9% vs. 1.3%; p<0.001) and non-invasive (6.9% vs.1.1%; p<0.001) and mechanical ventilation (5.2% vs. 1.8%; p<0.001) were used more frequently in patients with MSI≥0.93.

In the study population, 27.8% (n=322) of patients developed acute heart failure and 3.5% (n=41) developed cardiogenic shock. The proportion of patients with acute heart failure (36.1% vs. 24.6%; p<0.001) and cardiogenic shock (6.5% vs. 2.4%; p=0.001) was higher in patients with MSI≥0.93.

Binary logistic regression analysis was performed for development of cardiogenic shock during hospital stay using the previously identified predictors. Right ventricular dysfunction (adjusted odds ratio [OR] 5.0, 95% CI 2.05-12.21; p<0.001) and left ventricular dysfunction (adjusted OR 4.87, 95% CI 1.12-4.78; p=0.001) were the strongest independent predictors, although the presence of acute heart failure on admission (adjusted OR 3.41, 95% CI 1.63-7.16; p<0.001) and MSI≥0.93 (adjusted OR 2.731, 95% CI 1.12-4.78; p=0.023) provided additional information.

Patients with MSI≥0.93 had more episodes of malignant arrhythmias (10.2% vs. 6.1%; p=0.017), new-onset atrial fibrillation (14.2% vs. 8.4%; p=0.003), mechanical complications (2.8% vs. 0.9%; p=0.027) and respiratory tract infections (8.6% vs. 3.2%; p<0.001).

Of the total population, 3.2% (n=37) died during hospitalization, and six-month all-cause mortality was recorded in 7.2% (n=88) of patients.

Patients with MSI≥0.93 had a higher proportion of in-hospital mortality (5.2% vs. 2.4%; p=0.013; OR 2.25; 95% CI 1.17-4.36; p=0.016). Due to the low rate of in-hospital mortality it was not possible to calculate independent predictors of in-hospital mortality in this sample.

Patients with MSI≥0.93 had also higher six-month all-cause mortality (13.3% vs. 5.4%; p<0.001); OR 2.68; 95% CI (1.73 – 4.16); p<0.001).

Table 3 shows the results of Cox proportional hazards regression analysis for six-month all-cause mortality. After adjusting for different baseline characteristics and possible confounding factors, MSI≥0.93 remained as an independent predictor (adjusted hazard ratio [HR] 2.00; 95% CI 1.20-3.34; p=0.008).

Kaplan-Meier curves (Figure 2) show that patients with MSI≥0.93 had higher mortality early after hospital admission, but their worse prognosis remained throughout the follow-up period (log rank p<0.001).

Figure 2.

Kaplan-Meier curves for six-month mortality according to the Modified Shock Index.

(0.07MB).

Firstly, although our patients were included in a prospective registry, this was a retrospective, non-randomized, observational study conducted in a single center, and so the results may have been influenced by identified or unidentified confounding factors. Secondly, most variables were determined by consulting medical records, which may have been incomplete. Finally, as the study's primary endpoint was all-cause mortality, this may have included not only cardiovascular death, but also death from other causes, which could bias our findings.