Study Participants

The Heart and Soul Study is a prospective cohort study of psychosocial factors and health outcomes in patients with coronary disease. Methods and objectives have been described. Criteria for enrollment were 1) history of myocardial infarction, 2) angiographic evidence of at least 50% stenosis by area in at least one coronary vessel, 3) evidence of exercise-induced ischemia by treadmill electrocardiogram or stress nuclear perfusion imaging, 4) history of coronary revascularization, or 5) clinical diagnosis of coronary artery disease as documented by an internist or cardiologist. Individuals were excluded if they deemed themselves unable to walk one block, experienced an acute coronary syndrome within the previous 6 months, or were planning to move out of the local area within 3 years. All study participants 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 1024 participants were enrolled, including 549 (54%) with a history of myocardial infarction, 237 (23%) with a history of coronary revascularization but not myocardial infarction, and 238 (23%) with a diagnosis of coronary artery disease that was documented by their physician. A total of 990 patients had measurable stroke distance, after excluding 4 individuals with moderate or severe aortic regurgitation.

Data Collection

Each participant completed a detailed interview and questionnaire regarding age, sex, race, medical history, current smoking, and level of alcohol consumption. Echocardiographic studies were performed in the standard left lateral recumbent and supine positions with a commercially available ultrasound system with harmonic imaging (Acuson Sequoia, Siemens Corporation, Mountain View, CA). A single cardiologist (N.B.S.), blinded to clinical and laboratory information, evaluated each comprehensive resting echocardiogram.

Stroke distance from the LVOT was measured from the anteriorly angled apical four-chamber view using pulsed wave Doppler with the interrogation beam directed across the LVOT. The sample volume was placed in the LVOT, just proximal to the aortic valve. The filter was optimized to visualize a clear border of the spectral Doppler signal, and the outer boundary of the signal was traced to calculate the velocity time integral ( Figure 1 ). In patients with atrial fibrillation, five consecutive beats were recorded and the average was measured. Stroke volume was calculated by LVOT area (derived from LVOT diameter) * LVOT stroke distance. Minute distance was calculated as heart rate * LVOT stroke distance with units of m/min. Cardiac output was calculated as minute distance * LVOT area with units of L/min. PA stroke distance was measured from the parasternal short-axis view, with the pulsed-wave Doppler interrogation signal placed centrally in the proximal PA annulus to record the closure signal of the pulmonic valve. The LVOT diameter was measured in the parasternal long-axis view.

Measurement of LVOT stroke distance by planimetry of the Doppler signal from the apical view with the sample volume in the LVOT. Note the smaller stroke distance on the left (11.2 cm) compared with the right (23.3 cm) despite the difference in the y-axis cm/s scale. LVOT, Left ventricular outflow tract; PG , pressure gradient; VTI , velocity time integral.

The degree of mitral regurgitation was defined according to valvular guidelines from the American College of Cardiology. Left ventricular mass was calculated using the truncated ellipse method, and left ventricular ejection fraction (LVEF) was calculated using biplane method of disks from apical four- and two-chamber views. Body surface area was calculated using the DuBois and DuBois formula for indexing of left ventricular mass and end-diastolic volume. Moderate to severe diastolic dysfunction was defined by the presence of both pulmonary vein diastolic dominant flow and mitral diastolic early “E” greater than “A” velocity flow.

Outcomes

We conducted telephone follow-up interviews and questioned participants or their proxies regarding recent emergency department visits, hospitalizations, or death. 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. All-cause mortality results were complete for at least 1 year of follow-up for 930 of 936 individuals with measurable stroke distance. Five individuals were completely lost to follow-up, and 1 individual declined to participate further in the study. Death was considered due to cardiovascular causes if the death certificate listed acute myocardial infarction, congestive HF, or arrhythmia as the primary cause of death. Sudden death also was considered cardiovascular if it was unexpected, otherwise unexplained, or occurred within 1 hour of the onset of terminal symptoms.

Hospitalization for HF was defined as a clinical syndrome requiring a minimum one-night hospital stay and involving at least two of the following: paroxysmal nocturnal dyspnea, orthopnea, elevated jugular venous pressure, pulmonary rales, a third heart sound, cardiomegaly on chest radiography, or pulmonary edema on chest radiography. These clinical signs and symptoms must have represented a clear change from the normal clinical state of the patient and must have been accompanied by either failing cardiac output as determined by peripheral hypoperfusion (in the absence of other causes, eg, sepsis or dehydration) or peripheral or pulmonary edema treated with intravenous diuretics, inotropes, or vasodilators.

Statistical Analysis

Baseline characteristics are reported as the mean plus or minus standard deviation for continuous variables and as percentages for categoric variables. Differences in baseline characteristics between groups of study participants were determined using the Student t test for continuous variables and the chi-square test for dichotomous variables. Differences between categories of stroke distance above or below the lowest quartile were reported. We used Cox proportional hazards (survival) models to calculate hazard ratios (HRs), which are reported with 95% CIs. Multivariate adjustments, where applicable, were made for all baseline characteristics shown in Table 1 . Analyses were performed using software (Statistical Analysis, Version 9.2, SAS Institute Inc., Cary, NC). C-statistics were derived without censoring for stroke distance, stroke volume (incorporating LVOT diameter), minute distance, cardiac output, and LVEF. Outcome events were counted once for each individual (e.g., recurrent HF hospitalizations in the same participant were not counted). Predefined end points were HF hospitalization, mortality, and the combined end point of HF hospitalization or mortality.