Little is known regarding gender differences in left ventricular (LV) function after anterior wall ST-segment elevation myocardial infarction (STEMI), despite it being a major determinant of patients’ morbidity and mortality. We therefore sought to investigate the impact of gender on LV function after primary percutaneous coronary intervention (PCI) for first anterior wall STEMI. Seven hundred eighty-nine consecutive patients (625 men) with first anterior STEMI were included in the analysis. All patients underwent an echocardiographic study within 48 hours of PCI. Women were older and more likely to have diabetes, hypertension, chronic renal failure, and a higher Killip score. Women had prolonged ischemic time, which was driven by prolonged symptom-to-presentation time (2.75 [interquartile range 1.5 to 4] vs 2 [interquartile range 1 to 3.5] hours, p = 0.005). A higher percentage of women had moderate or worse LV dysfunction (LV ejection fraction <40%; 61.6% vs 48%, p = 0.002). In a univariable analysis female gender was associated with moderate or worse LV function (p = 0.002). However, after accounting for variable baseline risk profiles between the 2 groups using multivariable and propensity score techniques, ischemic time >3.5 hours, leukocytosis, and pre-PCI Thrombolysis In Myocardial Infarction flow grade <2 were independent predictors of moderate or worse LV dysfunction, whereas female gender was not. Data on LV function recovery at 6 months, which were available for 45% of female and male patients with moderate or worse LV dysfunction early after PCI, showed no significant gender related difference in LV function recovery. In conclusion, women undergoing PCI for the first event of anterior STEMI demonstrate worse LV function than that of men, which might be partially attributed to delay in presentation. Hence greater efforts should be devoted to increasing women’s awareness of cardiac symptoms during the prehospital course of STEMI.
Most studies that have examined the association between gender and outcomes after primary percutaneous coronary intervention (PCI) have mainly evaluated mortality and major adverse cardiac events (MACE) without focusing on the left ventricular (LV) function. As the LV function is one of the major determinants of patients’ morbidity and mortality, we sought to investigate the impact of gender on LV function after primary PCI for first anterior ST-segment elevation myocardial infarction (STEMI).
Methods
From March 2003 to September 2012, 1,725 consecutive patients with STEMI who underwent emergency PCI at the Rabin Medical Center, Israel, were prospectively observed and entered into a clinical database. Acute STEMI was defined as the presence of typical chest pain and accompanying symptoms for a duration of at least 30 minutes but <12 hours in the presence of ST-segment elevation ≥1 mm in at least 2 contiguous leads or new or undetermined duration of left bundle branch block in association with elevated cardiac enzymes (creatine phosphokinase, troponin I or T). The registry included demographic, clinical, angiographic, procedural, and echocardiographic data. This registry was approved by the ethics committee of the Rabin Medical Center.
For the current analysis we included only patients who presented with first anterior STEMI. Patients were excluded from the current analysis if they had had previous myocardial infarction (MI) or coronary artery bypass grafting. A total of 789 consecutive patients (625 men) were included in the present study. All patients were treated with aspirin 300 mg before the PCI and either prasugrel 60 mg or clopidogrel 600 mg (administered in the ambulance, emergency room [ER], coronary care unit, or in the catheterization laboratory). Unfractionated heparin (70 U/kg loading) was given before PCI and adjusted to achieve an activated clotting time of 200 to 275 seconds during the intervention. Glycoprotein IIb/IIIa receptor inhibition by eptifibatide was used at the discretion of the operator only after crossing the culprit lesion with a guidewire. Coronary angiography was performed through the femoral or radial rout. Selection of stent type, predilatation with undersized balloons, and postdilatation with larger balloons also were left to the operator’s discretion. All stents were implanted with moderate to high deployment pressure (10 to 16 atm). Procedural success was defined as an angiographic residual stenosis of 20% by visual estimation or quantitative coronary angiography with optimized angiographic flow (Thrombolysis In Myocardial Infarction [TIMI] flow grade 3). All patients were prescribed lifelong aspirin and either clopidogrel (75 mg/day) or prasugrel (10 mg/day) for 12 months. Baseline clinical characteristics, angiographic details, quantitative coronary angiography, TIMI flow grade, and clinical outcomes were collected. Two-dimensional transthoracic echocardiography was performed on all patients during the first 48 hours after primary PCI using a Philips CX 50 (Philips Healthcare, Andover, MA). Echocardiographic studies were performed by an experienced sonographer and reviewed by a cardiologist specialized in echocardiography. LV function was estimated based on assessment of LV contractile performance and regional wall motion abnormality in multiple 2-dimensional views. Subjects were classified as having normal LV function (left ventricular ejection fraction [LVEF] ≥55%), preserved LV function (50% ≤ LVEF <55%), mild LV dysfunction (45% ≤ LVEF <50%), mild to moderate LV dysfunction (40% ≤ LVEF <45%), moderate LV dysfunction (35% ≤ LVEF <40%), moderate to severe LV dysfunction (30% ≤ LVEF <35%), and severe LV dysfunction (LVEF <30%).
The primary end point of this analysis was LV function as assessed by transthoracic echocardiogram during the first 48 hours after PCI. The secondary end points were 30-day mortality rate and 1- and 2-year rates of MACE and its components, consisting of death, recurrent MI, target vessel revascularization, stent thrombosis, coronary artery bypass grafting, and LV function recovery at 6 months. All events were further adjudicated by a research coordinator and reviewed by an experienced cardiologist from our research team. The investigators adjudicating the clinical events were blinded to the gender. Immediate and in-hospital events were recorded from the hospital charts. LV function was recorded from the echocardiographic reports. For each patient, a standardized questionnaire was completed either by telephone or in the outpatient clinic at 1, 6, 12, and 24-month follow-ups. Mortality was confirmed by the records of the Interior Ministry of Israel. Repeat revascularization procedures and episodes of reinfarction were confirmed using the hospital and affiliated hospitals’ databases. These databases were searched for all patients in the study to gather information regarding repeat events. Follow-up was completed for 100% of the patients at 1 month. Data on mortality at 1 and 2 years were available for all patients. Clinical data on 1- and 2- year outcomes were available for 94.5% and 87% of the patients, respectively. The diagnosis of reinfarction during follow-up was based on recurrent chest pain, suggestive of acute MI, accompanied by re-elevation of the cardiac enzyme with at least 1 value above the ninety-ninth percentile upper reference limit at least 48 hours after PCI and/or new ST elevation, new left bundle branch block, or development of pathological Q waves in the electrocardiogram. Target vessel revascularization was defined as any revascularization that involved the target vessel. Stent thrombosis was defined according to the Academic Research Consortium definitions as “definite” in the context of acute coronary syndrome and/or reinfarction in the culprit coronary territory with angiographically proven thrombosis (thrombus or occlusion) of the previously implanted stent. Data regarding LV function recovery at 6 months after PCI were recorded from echocardiographic reports performed at out hospital or affiliated hospitals and clinics.
Data are presented as mean ± SD for normally distributed variables and as median (interquartile range [IQR]) for non-normally distributed variables. Continuous variables were compared using the Student t test or Wilcoxon signed rank tests, as appropriate. For LV function recovery Wilcoxon matched-pair signed rank tests were used. Categorical variables were compared using the chi-square statistics or Fischer’s exact test, as appropriate. All tests were 2-tailed, and a p value <0.05 was considered significant. Survival analysis in women versus men was performed using life-table analysis. Logistic regression analyses for moderate or worse LV dysfunction and 1- and 2-year mortality were performed with covariates with a p value <0.10 on univariable analysis. A propensity analysis was carried out for gender based on baseline clinical and preprocedural angiographic characteristics including age, year of PCI, diabetes mellitus, hypertension, hyperlipidemia, smoking, previous cerebrovascular accident, peripheral vascular disease, renal failure (glomerular filtration rate <60 ml/min), anemia (a baseline hematocrit level <39% for men and <36% for women), white blood cell count >10.0 × 10 9 /L, number of stenosed coronary arteries, antiplatelet pretreatment, day time PCI, total ischemic time >3.5 hours, pre-PCI TIMI flow grade <2, and post-TIMI flow grade <3. The score was then incorporated into a subsequent multivariable regression analysis as a covariate. Multivariable models adjusting for propensity score and any additional variable with a p value <0.10 in univariable selection models were created for each of moderate or worse LV dysfunction. Analyses were performed using Statistica software (StatSoft, Inc., Tulsa, Oklahoma).
Results
A total of 789 patients (164 women and 625 men) were included in this analysis. Baseline characteristics of patients according to gender are listed in Table 1 . Women presented at an older age (69 vs 59 years, p <0.001) and were more likely to have diabetes (40% vs 23%, p = 0.003), hypertension (60% vs 43%, p = 0.002), and renal failure (24% vs 11%, p <0.001). Fewer women had a history of smoking (27% vs 48%, p <0.001). More women presented with a Killip class >1 (24% vs 13%, p = 0.001). Time from symptom onset to arrival at the ER was significantly longer in women compared with men (median time of 2.75 [IQR 1.5 to 4] vs 2 [IQR 1 to 3.5] hours, p = 0.005) as well as the total ischemic time (median time of 4 [IQR 3 to 6] vs 3.5 [IQR 2.45 to 5] hours, p = 0.001). However, the door-to-balloon time did not differ between the 2 groups (median time of 1 [IQR 1 to 2] vs 1 [IQR 0.75 to 2] hour, p = 0.1; Figure 1 and Table 1 ).
| Variable | Men (n = 625) | Women (n = 164) | p Value | |
|---|---|---|---|---|
| Age (years) | 59 ± 12 | 62 ± 14 | <0.001 | |
| Age >65 | 169 (27%) | 111 (68%) | <0.001 | |
| Diabetes | 144 (23%) | 66 (40%) | 0.003 | |
| Hypertension | 269 (43%) | 98 (60%) | 0.002 | |
| Hyperlipidemia | 269 (43%) | 80 (49%) | 0.2 | |
| Smoker | 300 (48%) | 44 (27%) | <0.001 | |
| Anemia ∗ | 137 (22%) | 34 (21%) | 0.99 | |
| GFR <60 ml/min/1.73 m 2 | 69 (11%) | 39 (24%) | <0.001 | |
| WBC >10.0 × 10 9 /L | 431 (69%) | 112 (69%) | 0.9 | |
| Medical treatment at baseline | ||||
| Aspirin | 569 (91%) | 143 (87%) | 0.03 | |
| Statins | 181 (29%) | 62 (38%) | 0.03 | |
| ACE inhibitors | 51 (8%) | 12 (7%) | 0.7 | |
| Beta-blockers | 55 (9%) | 13 (8%) | 0.7 | |
| Time intervals | ||||
| Symptom onset to ER (hours) | 2 [1–3.5] | 2.75 [1.5–4] | 0.005 | |
| Door to balloon (hours) | 1 [0.75–2] | 1 [1–2] | 0.1 | |
| Total ischemic time (hours) | 3.5 [2.45–5] | 4 [3–6] | 0.001 | |
| Total ischemic time >3.5 hours | 319 (51%) | 112 (68%) | 0.005 | |
| Clinical presentation | ||||
| Killip class >1 | 81 (13%) | 38 (23%) | 0.001 | |
| Cadillac score | 4.7 ± 3.5 | 6.5 ± 3.8 | 0.001 | |
∗ Anemia was defined as a baseline hematocrit level <39% for men and <36% for women.
Procedural and angiographic findings are listed in Table 2 . Although there was no difference in the TIMI flow grade before PCI, the angiographic results were better in men with higher rates of TIMI flow grade 3 after PCI (96% vs 89.6%, p = 0.006).
| Variable | Men (n = 625) | Women (n = 164) | p Value |
|---|---|---|---|
| No. of coronary arteries narrowed | 0.2 | ||
| 1 | 306 (49%) | 90 (55%) | |
| 2 | 194 (31%) | 51 (31%) | |
| 3 | 125 (20%) | 23 (14%) | |
| TIMI flow grade culprit lesion before PCI | 0.5 | ||
| 0 | 325 (52%) | 85 (52%) | |
| 1 | 41 (7%) | 14 (9%) | |
| 2 | 112 (18%) | 34 (21%) | |
| 3 | 147 (24%) | 31 (19%) | |
| TIMI flow grade culprit lesion after PCI | 0.006 | ||
| 0 | 4 (0.64%) | 5 (3%) | |
| 1 | 1 (0.16%) | 1 (0.6%) | |
| 2 | 20 (3%) | 11 (7%) | |
| 3 | 600 (96%) | 147 (90%) | |
| Calcifications | 94 (15%) | 43 (26%) | 0.001 |
| Stents | 609 (98%) | 157 (96%) | 0.2 |
| Drug eluting stent | 131 (21%) | 26 (16%) | 0.1 |
| Stent length (mm) | 19.5 ± 6.0 | 18.0 ± 5.3 | 0.002 |
| Stent diameter (mm) | 3.1 ± 0.4 | 2.9 ± 0.4 | <0.001 |
A higher percentage of women had moderate or worse LV dysfunction (LVEF <40%) as assessed by transthoracic echocardiogram during the first 48 hours after PCI compared with men (61.6% vs 48%, p = 0.002; Table 3 and Figure 2 ). In a univariable analysis, moderate or worse LV dysfunction was associated with age >65 years, female gender, prolonged total ischemic time, total ischemic time >3.5 hours, prolonged time from symptom onset to ER, diabetes, renal failure, Killip class >1, pre-PCI TIMI flow grade <2, post-TIMI flow grade <3, and white blood cell count >10.0 × 10 9 /L.
| Variable | Men (n = 625) | Women (n = 164) | p Value |
|---|---|---|---|
| Moderate or worse LV dysfunction (EF <40%) | 300 (48%) | 101 (62%) | 0.002 |
| Mean EF (%) | 39.9 ± 9.5 | 37.4 ± 10.2 | 0.003 |
| Median EF (%) | 45 [IQR 35–45] | 35 [IQR 30–45] | 0.025 |
In a multivariable analysis, female gender emerged as an independent predictor of moderate or worse LV dysfunction, as well as total ischemic time >3.5 hours, pre-PCI TIMI flow grade <2, white blood cell count >10.0 × 10 9 /L, diabetes, and renal failure ( Table 4 ). However, after accounting for variable baseline risk profiles between the 2 groups using multivariable and propensity score techniques, female gender did not remain an independent predictor of moderate or worse LV dysfunction, whereas total ischemic time >3.5 hours, white blood cell count >10.0 × 10 9 /L, and pre-PCI TIMI flow grade <2 remained ( Table 4 ).
| Variable | Multivariable Logistic Regression ∗ | Multivariable Logistic Regression and Propensity Score | ||
|---|---|---|---|---|
| OR (95% CI) | p Value | OR (95% CI) | p Value | |
| Female gender | 1.47 [1.01–2.1] | 0.044 | 1.3 [0.8–2.0] | 0.2 |
| GFR <60 ml/min/1.73 m 2 | 1.2 [1.03–1.4] | 0.02 | 1.1 [0.96–1.3] | 0.1 |
| Total ischemic time >3.5 hours | 1.4 [1.1–1.9] | 0.001 | 1.4 [1.01–1.9] | 0.049 |
| Diabetes mellitus | 1.4 [1.01–2.0] | 0.04 | 1.3 [0.86–1.8] | 0.2 |
| WBC count >10 × 10 9 /L | 1.6 [1.2–2.1] | 0.006 | 1.6 [1.2–2.2] | 0.004 |
| Pre-PCI TIMI flow grade <2 | 1.3 [1.2–1.6] | 0.009 | 1.3 [1.1–1.5] | 0.001 |
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