Background
Changes in left atrial (LA) volumes after ST elevation myocardial infarction are reported but have not been well described following non–ST elevation myocardial infarction (NSTEMI).
Methods
Seventy-five patients with NSTEMIs were studied within 48 hours of presentation and in follow-up at 6 and 12 months; they were compared with age-matched normal controls ( n = 100). Biplane indexed LA volumes were measured, and phasic LA volumes (conduit, passive, and active emptying) were calculated. LA remodeling was defined as an increase in LA maximum volume over 12 months.
Results
LA maximum volume was significantly larger at baseline in patients with NSTEMIs. At 12 months, maximum LA volume increased (27.6 ± 7.4 vs 30.2 ± 8.9 mL/m 2 , P = .002), with LA remodeling present in 64% of the patients with NSTEMIs. LA passive emptying volume increased, with concurrent reductions in conduit and active emptying volumes. Although diabetes, major coronary artery disease, and a larger myocardial score were predictive of LA remodeling, E′ velocity was the only independent predictor.
Conclusions
Patients with NSTEMIs had progressive LA enlargement with reductions in conduit and active emptying volumes, reflecting persistent left ventricular diastolic dysfunction consequent to coronary artery disease and associated diabetes. The measurement of LA volumes after NSTEMI may be useful to monitor chronic diastolic dysfunction resulting from ischemic burden.
Myocardial infarction and ischemia are associated with left atrial (LA) dilatation, a surrogate marker of left ventricular (LV) diastolic dysfunction and an emerging biomarker of overall cardiovascular disease. Non–ST elevation myocardial infarction (NSTEMI) with resultant subendocardial myocardial necrosis represents a group of patients with coronary artery disease (CAD) with a high incidence of future adverse cardiac events. Previous studies have demonstrated that following NSTEMI, there can be associated LA dilatation and abnormal atrial depolarization. However, no study has systematically examined temporal changes in LA volume or alterations in LA phasic function following NSTEMI. LA remodeling following NSTEMI could increase the occurrence of atrial fibrillation. In the setting of NSTEMI with consequent LV dysfunction, atrial fibrillation could further reduce LV filling, precipitating diastolic heart failure. Therefore, serially monitoring LA volumes and function following NSTEMI may provide valuable prognostic information and enable appropriate targeted treatment.
LA function includes phases of reservoir (during ventricular systole), conduit (during early diastole and diastasis), and active contraction (during late diastole). The aims of this study were to examine maximum and phasic LA volumes and function and to determine temporal changes following NSTEMI. We hypothesized that following NSTEMI, (1) maximum LA volume would be increased and phasic LA volumes altered at baseline, (2) these LA changes would regress over time, and (3) LA changes may be dependent on the extent of CAD.
Methods
Study approval was obtained from the Human Research Committee at Liverpool Hospital (Sydney, Australia). Seventy-five consecutive patients presenting with NSTEMI (defined as presentation with chest pain and an increase in cardiac troponin T, with or without associated electrocardiographic changes ) were prospectively recruited. Exclusion criteria were cardiac rhythm other than sinus, valvular disease of more than moderate regurgitation, or stenosis and suboptimal echocardiographic images. Patients were monitored by their treating cardiologists, and the investigators made no attempt to control or regulate drug therapy. Patients with NSTEMIs underwent baseline echocardiography within 48 hours of presentation and follow-up echocardiography at 6 and 12 months.
Patients were compared with frequency-matched normal controls ( n = 100), who were recruited from the general community. Normal controls were screened by a detailed medical history and had to be free from any known cardiovascular risk or disease. In addition to transthoracic echocardiography, all subjects underwent a detailed clinical evaluation, including cardiovascular symptoms and history, medication history, family history, height, weight, blood pressure monitoring, electrocardiography, and normal blood tests to exclude any underlying pathology. Normal subjects were excluded if they had histories of ischemic heart disease, arrhythmias, significant valvular disease, peripheral vascular or cerebrovascular disease, hypertension, or diabetes and were on any cardioactive medications.
Echocardiography
Transthoracic echocardiography was performed according to established laboratory practice using commercially available ultrasound systems (Vivid 7; GE Vingmed Ultrasound AS, Horten, Norway). Measurements were performed offline using EchoPAC version BT 06.1.0 (GE Vingmed Ultrasound AS).
LV volumes were measured using the modified Simpson’s biplane method of disks and indexed to body surface area. LV ejection fraction, stroke volume, mass index, and relative wall thickness were determined. LV systolic function was graded as normal (LV ejection fraction ≥ 50%), mild dysfunction (LV ejection fraction, 45%–50%), moderate dysfunction (LV ejection fraction, 30%–44%), or severe dysfunction (LV ejection fraction < 30%). LA volumes were measured using Simpson’s biplane method of disks from the apical four-chamber and two-chamber views ( Figure 1 ). Biplane LA maximum (just before mitral valve opening), LA minimum (at mitral valve closure), and LA pre-P (onset of P wave on electrocardiography) volumes were measured ( Figure 2 ) and indexed to body surface area (milliliters per square meter). Phasic LA volumes and fractions were calculated as follows :
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Reservoir: LA total emptying volume = LA maximum volume − LA minimum volume; LA expansion index = LA total emptying volume/LA minimum volume.
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Conduit: passive emptying volume = LA maximum volume − LA pre-P volume; passive emptying fraction = passive emptying volume/LA maximum volume; conduit volume = LV stroke volume − LA total emptying volume.
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Active: active emptying volume = LA pre-P volume − LA minimum volume; active emptying fraction = active emptying volume/LA pre-P volume.
LA enlargement was defined as an indexed LA volume > 33 mL/m 2 in men and >30 mL/m 2 in women. LV and LA remodeling were defined as increases in LV end-systolic and LA maximum volumes, respectively, over 12 months from baseline.
Pulsed Doppler mitral inflow was obtained with the sample volume placed at the leaflet tips; peak E and A velocities, E/A ratio, deceleration time, and A-wave duration were measured. Isovolumic relaxation time was measured from the continuous-wave Doppler LV outflow tract signal.
Pulmonary vein flow by pulsed-wave Doppler was obtained by placing the sample within the proximal 2 cm of the right upper pulmonary vein. Peak systolic, diastolic, and atrial reversal velocities, atrial reversal duration, and the systolic/diastolic ratio were obtained.
Color tissue Doppler images of the left ventricle were obtained in the apical four-chamber and two-chamber and long-axis views. As the study group comprised patients with NSTEMIs with regional wall motion abnormalities, we measured global S′ and E′ velocities as the average of six basal segments (septal, lateral, inferior, anterior, posterior, and anteroseptal). Color Doppler tissue images permitted offline analysis, thereby reducing the study duration. An average of three measurements was used in the final analysis.
LV diastolic dysfunction was classified as normal (deceleration time, 160–240 ms; E/A ratio, 0.9–1.5; E′ velocity ≥ 10 cm/s), impaired (deceleration time > 240 ms; E/A ratio < 0.9; E′ velocity < 10 cm/s), pseudonormal (deceleration time, 160–240 ms; E/A ratio, 0.9–1.5; E′ velocity < 8 cm/s), or restrictive (deceleration time < 160 ms; E/A ratio > 2.0; E′ velocity < 5 cm/s).
Cardiac Catheterization
Selective coronary angiography using the Judkins technique was performed in all patients at initial presentation. Significant CAD was defined as ≥70% luminal stenosis in an epicardial coronary artery or ≥50% left main coronary artery stenosis. Infarct-related artery flow was assessed by experienced interventionalists blinded to clinical and echocardiographic outcomes. The extent of CAD was assessed using two methods. The first method used grading as performed in routine clinical practice determined by the number of large epicardial arteries with significant stenosis. Patients were grouped into two categories: minor CAD (minor or single-vessel disease) and major CAD (double-vessel, triple-vessel, or significant left main disease). The second method evaluated the severity of CAD using a myocardial score that measures the amount of LV myocardium “at risk” by severity of arterial obstructions. Additionally the myocardial score takes into account arterial branches in terms of the amount of myocardium supplied by them, which reflects their importance. The myocardial score ranges from 0 to 15, with an increasing score representing more severe arterial disease.
Statistical Analysis
All values are expressed as a mean ± SD unless otherwise stated. Differences between groups were examined using unpaired Student’s t tests for parametric variables and χ 2 analysis for categorical variables. Repeated-measures analysis of variance with Bonferroni’s correction was used to examine effects of parametric variables over time. Cochrane’s Q test was used to examine nominal data, and Friedman’s test was used to examine categorical data over time. Multiple linear regressions with stepwise variable selection were performed to determine predictors of LA remodeling, with significant univariate predictors entered into the model. Data were considered significant if P < .05. Data were analyzed using SPSS version 15.0 (SPSS, Inc., Chicago, IL).
Results
Demographic variables for both groups are listed in Table 1 . Following presentation with NSTEMI, 72% of patients (54 of 75) underwent revascularization at the initial admission. A further 15% (11 of 75) underwent repeat coronary interventions within 12 months. Significant luminal stenosis of the proximal circumflex artery was present in 23% of the study patients (17 of 75). The mean myocardial score was 8.4 ± 3.5 (range, 0–14.0), out of a maximum score of 15. Twelve patients (16%) had adverse cardiovascular outcomes, including two (3%) with heart failure and 10 (13%) with readmissions for acute coronary syndromes. There were no deaths, and no patient required cardiac transplantation at 12 months.
| Patients with NSTEMIs ( n = 75) | ||||
|---|---|---|---|---|
| Variable | Normal controls ( n = 100) | Baseline | 6 months | 12 months |
| Demographics | ||||
| Age (years) | 61 ± 11 | 60 ± 12 | ||
| Men | 68% | 71% | ||
| Body surface area (m 2 ) | 1.9 ± 0.2 | 1.9 ± 0.2 | ||
| Body mass index (kg/m 2 ) | 26 ± 4 | 27 ± 4 | ||
| Heart rate (beats/min) | 68 ± 11 | 65 ± 12 ∗ | 65 ± 11 | 62 ± 9 ∗ |
| Systolic blood pressure (mm Hg) | 123 ± 12 | 124 ± 19 | 126 ± 20 | 126 ± 20 |
| Diastolic blood pressure (mm Hg) | 76 ± 8 | 72 ± 12 | 74 ± 9 | 74 ± 10 |
| Mean arterial pressure (mm Hg) | 92 ± 8 | 86 ± 18 ∗ | 91 ± 12 | 92 ± 12 |
| Cardiovascular risk factors | ||||
| Diabetes mellitus | 24% | |||
| Hypertension | 36% | |||
| Smoking | 36% | |||
| Hypercholesterolemia | 67% | |||
| Family history | 23% | |||
| Previous myocardial infarction | 24% | |||
| Previous coronary artery bypass grafting | 9% | |||
| CAD | ||||
| Minor/single-vessel | 49% | |||
| Two-vessel or three-vessel/left main disease | 51% | |||
| Myocardial score | 8.4 ± 3.5 | |||
| Left anterior descending coronary artery | 55% | |||
| Circumflex artery | 40% | |||
| Right coronary artery | 36% | |||
| Treatment | ||||
| Percutaneous coronary intervention | 49% | 11% | ||
| Coronary artery bypass grafting | 23% | 4% | ||
| Biochemical markers | ||||
| Peak plasma cardiac troponin T (ng/ml) | 1.1 ± 1.5 | |||
| Peak creatinine kinase (U/L) | 493 ± 645 | |||
| Peak creatinine kinase-MB (ng/mL) | 35.1 ± 66.0 | |||
| Creatinine (μmol/L) | 94.9 ± 31.0 | |||
| Hemoglobin level (g/L) | 139.0 ± 17.6 | |||
| Medications | ||||
| Aspirin | 96% | 92% | 91% | |
| Clopidogrel | 65% | 56% | 59% | |
| β-blockers | 85% | 67% † | 73% † | |
| Calcium channel blockers | 12% | 8% | 14% | |
| Angiotensin-converting enzyme inhibitors | 48% | 44% | 46% | |
| Angiotensin receptor blockers | 17% | 25% | 27% | |
| Statins | 100% | 92% † | 88% † | |
| Diuretics | 21% | 21% | 21% | |
| Nitrates | 12% | 6% | 11% | |
| Nicorandil | 2% | 2% | 5% | |
| Warfarin | 6% | 4% | 2% | |
| Mitral regurgitation grade | ||||
| Physiological | 68% | 85% | ||
| Mild | 27% | 12% | ||
| Moderate | 5% | 3% | ||
Baseline
LV Volumes and Function
LV end-systolic volume index was larger ( P < .001) and LV ejection fraction lower ( P < .001) in the NSTEMI group at baseline compared with controls ( Table 2 ).
| Patients with NSTEMIs ( n = 75) | ||||
|---|---|---|---|---|
| Variable | Normal controls ( n = 100) | Baseline | 6 months | 12 months |
| Left ventricle | ||||
| LV end-diastolic volume index (mL/m 2 ) | 47.3 ± 10.1 | 46.7 ± 12.6 | 46.6 ± 13.8 | 43.0 ± 12.4 ∗ † ‡ |
| LV end-systolic volume index (mL/m 2 ) | 17.9 ± 4.8 | 23.1 ± 10.9 ∗ | 22.3 ± 11.4 ∗ | 20.2 ± 10.1 † ‡ |
| LV mass index (g/m 2 ) | 72.0 ± 15.0 | 90.4 ± 23.4 ∗ | 89.6 ± 24.0 ∗ | 89.6 ± 25.0 ∗ |
| LV ejection fraction (%) | 62 ± 6 | 52 ± 11 ∗ | 54 ± 11 ∗ | 55 ± 10 ∗ † |
| LV stroke volume index (mL/m 2 ) | 29.4 ± 6.9 | 23.6 ± 5.7 ∗ | 24.3 ± 6.3 ∗ | 22.7 ± 4.9 ∗ |
| S′ velocity (cm/sec) | 6.2 ± 1.3 | 4.6 ± 1.1 ∗ | 4.7 ± 1.2 ∗ | 4.6 ± 1.2 ∗ |
| Systolic function | ||||
| Normal | 100% | 68% ∗ | 75% ∗ | 76% ∗ |
| Mild dysfunction | 0% | 13% | 9% | 13% |
| Moderate dysfunction | 0% | 16% | 13% | 9% |
| Severe dysfunction | 0% | 3% | 3% | 1% |
| Left atrium | ||||
| LA maximum volume index (mL/m 2 ) | 23.7 ± 5.5 | 27.6 ± 7.4 ∗ | 29.0 ± 8.3 ∗ | 30.2 ± 8.9 ∗ † |
| LA minimum volume index (mL/m 2 ) | 10.9 ± 3.4 | 15.1 ± 5.7 ∗ | 15.5 ± 6.8 ∗ | 15.4 ± 6.7 ∗ |
| LA pre-P volume index (mL/m 2 ) | 16.7 ± 4.5 | 20.6 ± 6.5 ∗ | 21.7 ± 7.8 ∗ | 19.9 ± 7.8 ∗ ‡ |
| Reservoir | ||||
| LA total emptying volume index (mL/m 2 ) | 13.8 ± 4.3 | 12.4 ± 3.0 ∗ | 13.3 ± 3.2 | 14.7 ± 4.2 † ‡ |
| LA expansion index (%) | 134.3 ± 47.8 | 90.8 ± 32.2 ∗ | 97.1 ± 34.3 ∗ | 109.2 ± 47.2 ∗ † ‡ |
| Conduit | ||||
| Conduit volume index (mL/m 2 ) | 16.6 ± 6.1 | 11.1 ± 5.4 ∗ | 10.9 ± 6.3 ∗ | 7.9 ± 5.7 ∗ † ‡ |
| Passive emptying volume index (mL/m 2 ) | 6.9 ± 3.1 | 7.0 ± 2.7 | 7.3 ± 2.7 | 10.3 ± 4.1 ∗ † ‡ |
| Passive emptying fraction (%) | 30.0 ± 9.9 | 25.6 ± 8.6 ∗ | 26.0 ± 9.7 ∗ | 34.9 ± 12.4 ∗ † ‡ |
| Active | ||||
| Active emptying volume index (mL/m 2 ) | 5.9 ± 2.2 | 5.6 ± 2.1 | 6.1 ± 2.5 | 4.5 ± 3.0 ∗ ‡ |
| Active emptying fraction (%) | 36.2 ± 9.9 | 27.9 ± 9.0 ∗ | 29.4 ± 9.6 ∗ | 22.7 ± 12.7 ∗ † ‡ |
† P < .05 vs patients with NSTEMIs at baseline.
LV diastolic parameters for both groups are listed in Table 3 . Peak E velocity ( P = .02), E/E′ ratio ( P < .001), and E/A ratio ( P = .002) were higher in the NSTEMI group at baseline compared with controls, while E′ velocity was significantly lower ( P < .001).
| Patients with NSTEMI ( n = 75) | ||||
|---|---|---|---|---|
| Variable | Normal controls ( n = 100) | Baseline | 6 months | 12 months |
| Mitral inflow | ||||
| E velocity (cm/sec) | 66.9 ± 16.5 | 73.9 ± 22.4 ∗ | 74.7 ± 20.2 ∗ | 72.7 ± 20.2 ∗ |
| A velocity (cm/sec) | 67.8 ± 19.7 | 65.1 ± 22.2 | 65.2 ± 21.4 | 68.2 ± 21.0 |
| E/A ratio | 1.0 ± 0.3 | 1.2 ± 0.5 ∗ | 1.3 ± 0.6 ∗ | 1.1 ± 0.4 |
| Deceleration time (msec) | 212 ± 46 | 190 ± 47 ∗ | 201 ± 52 | 202 ± 46 |
| A duration (msec) | 180 ± 41 | 128 ± 16 ∗ | 135 ± 14 ∗ † | 137 ± 15 ∗ † |
| Isovolumic relaxation time (msec) | 89 ± 16 | 79 ± 20 ∗ | 87 ± 20 † | 83 ± 17 |
| Doppler tissue imaging | ||||
| E′ velocity (cm/sec) | 7.9 ± 1.8 ‡ | 5.5 ± 1.8 ∗ | 5.9 ± 2.1 ∗ | 5.7 ± 2.0 ∗ |
| E/E′ ratio | 9 ± 2 ‡ | 15 ± 8 ∗ | 15 ± 9 ∗ | 15 ± 10 ∗ |
| Pulmonary vein flow | ||||
| Systolic velocity (cm/sec) | 55.0 ± 12.4 | 46.0 ± 19.2 ∗ | 52.8 ± 17.9 † | 53.8 ± 11.3 † |
| Diastolic velocity (cm/sec) | 44.9 ± 11.5 | 45.6 ± 14.8 | 49.1 ± 15.4 ∗ | 47.6 ± 11.9 |
| Systolic/diastolic ratio | 1.3 ± 0.4 | 1.1 ± 0.6 ∗ | 1.2 ± 0.5 ∗ | 1.2 ± 0.4 |
| Atrial reversal velocity (cm/sec) | 28.4 ± 7.0 | 27.0 ± 10.8 | 27.3 ± 9.0 | 26.7 ± 5.7 |
| Atrial reversal duration (msec) | 138 ± 36 | 135 ± 16 | 143 ± 22 † | 140 ± 21 |
| Atrial reversal duration − A duration (msec) | −40 ± 44 | 7 ± 19 ∗ | 8 ± 22 ∗ | 2 ± 25 ∗ |
| Diastolic function | ||||
| Normal | 71% | 16% ∗ | 20% ∗ | 16% ∗ |
| Impaired | 29% | 12% | 16% | 20% |
| Pseudonormal | 0% | 64% ∗ | 59% ∗ | 61% ∗ |
| Restrictive | 0% | 8% | 5% | 3% |
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