The Heart and Soul Study was a prospective cohort study of psychosocial factors and health outcomes in patients with coronary disease. Methods and objectives have been described previously.7
Criteria for enrollment were (1) history of MI, (2) angiographic evidence of ≥50% diameter stenosis in ≥1 coronary vessel, (3) evidence of exercise-induced ischemia using treadmill electrocardiogram or stress nuclear perfusion imaging, or (4) history of coronary revascularization. Patients were excluded if they deemed themselves unable to walk 1 block, were within 6 months of an acute coronary syndrome, or were planning to move out of the local area within 3 years. All study subjects provided informed consent for baseline echocardiographic testing and review of medical records. The institutional review board at each of the enrolling centers approved the study protocol. Between September 2000 and December 2002, a total of 1,024 subjects were enrolled. Of these, 49 subjects were excluded for atrial fibrillation, atrial flutter, mitral stenosis, or greater than mild mitral regurgitation, categorized using reference criteria from the American Society of Echocardiography.4
Each subject completed a detailed interview and questionnaire detailing age, gender, race, medical history, medications, current smoking, and level of alcohol consumption. Echocardiographic studies were performed in the standard left lateral recumbent and supine positions using a commercially available ultrasound system with harmonic imaging (Acuson Sequoia; Siemens Corp., Mountain View, California). By protocol, LA size was maximized in both 2- and 4-chamber views. A single cardiologist (NBS) blinded to clinical and laboratory information evaluated each echocardiogram at rest. Our reader’s reproducibility was previously established.8
LA volume was measured from standard apical 2- and 4-chamber views at end-systole. LA borders were traced using planimetry. The borders consisted of the walls of the left atrium and a line drawn across the mitral annulus (). Attention was given to bridge the ostia of pulmonary veins (when visualized) to not include the veins in the measurement. If seen, the LA appendage was excluded from measurement. The biplane method of disks was used to calculate LA volume,4
and measurements were rounded to the nearest integer. LAVI was calculated by dividing LA volume by body surface area. The American Society of Echocardiography criterion for severe LA dilatation (LAVI >40 ml/m2
) was used to compare baseline characteristics of subjects.
Measurement of LA volume using the biplane method of disks in apical 4- and 2-chamber views.
LVEF was calculated using the biplane method of disks from apical 4- and 2-chamber views. Diastolic dysfunction was categorized according to the classification by Khouri et al9
; the presence of pseudonormal or restrictive diastolic dysfunction was defined as diastolic dominant pulmonary vein flow and mitral diastolic early/late velocity flow ratio >0.75. Diastolic function was not able to be categorized in 55 subjects because of the absence of measurable or discordance between mitral inflow and pulmonary venous flow parameters. Inducible myocardial ischemia was defined as a new wall abnormality not present on treadmill stress echocardiography images at rest.
We conducted telephone follow-up interviews and questioned subjects or their proxies regarding recent emergency department visits, hospitalizations, or death. For any reported event, medical records, death certificates, and coroner’s reports were retrieved. Two blinded adjudicators reviewed each event, and if there was agreement, the outcome classification was binding. If there was disagreement, a third blinded adjudicator reviewed the event and determined the outcome classification. Outcome adjudications were available for all except 5 subjects.
Mortality adjudications were based on hospital records, death certificates, and autopsy results. Hospitalization for HF was defined as a clinical syndrome requiring a minimum 1-night hospital stay with ≥2 of paroxysmal nocturnal dyspnea, orthopnea, increased jugular venous pressure, pulmonary rales, a third heart sound, cardiomegaly on chest radiograph, or pulmonary edema on chest radiograph.10
These clinical signs and symptoms must have represented a clear change from the previous clinical state of the patient. Stroke was considered an acute neurologic deficit of ischemic or hemorrhagic origin requiring supportive clinical and imaging documentation.
The outcome of MI was determined using standard diagnostic criteria developed by the American Heart Association.11
Death was considered caused by heart disease if (1) the subject died during the same hospitalization in which an acute MI was documented or (2) the subject experienced sudden death, defined as unexpected otherwise unexplained death within 1 hour of the onset of terminal symptoms.
Baseline characteristics were reported as mean ± SD for continuous variables and percentage for categorical variables. Differences in baseline characteristics between groups were determined using Student’s t
test for continuous variables and chi-square test for dichotomous variables. The cutoff of 40 ml/m2
was used based on American Society of Echocardiography criteria for severe LAVI dilatation.4
Differences between categories of LA dilatation by reference standards for LAVI and LVEF were determined using chi-square test. We used logistic regression to examine the association of LAVI with HF, stroke, and mortality.
We report odds ratios (ORs) with 95% confidence intervals. Multivariate adjustments, when applicable, were made for all baseline characteristics listed in . We calculated c statistics (the numerical equivalent of area under the receiver-operator characteristic curve) for LAVI and LVEF. Analyses were performed using SAS software (version 8; SAS Institute Inc., Cary, North Carolina). Outcome events were counted once for each subject (e.g., recurrent HF hospitalizations in the same subject were not counted). Predefined end points were HF hospitalization, stroke, MI, cardiovascular mortality, and all-cause mortality.
Baseline characteristics by left atrial volume index (LAVI)