Publications

BACKGROUND

To our knowledge, the risk of sudden cardiac death (SCD) and the assessment of risk factors in prediction models have not been evaluated in women with coronary artery disease (CAD). We sought to evaluate the incidence of SCD as well as its risk factors and their predictive accuracy among a population of women with CAD.

METHODS

The Heart and Estrogen/progestin Replacement Study evaluated the effects of hormone replacement therapy on cardiovascular events among 2763 postmenopausal women with CAD. Sudden cardiac death was defined as death resulting from a cardiac origin that occurred within 1 hour of symptom onset. The associations between candidate predictor variables and SCD were evaluated in a Cox proportional hazards model. The C-index was used to compare the predictive value of the clinical risk factors with left ventricular ejection fraction (LVEF) alone and in combination. The net reclassification improvement was also computed.

RESULTS

Over a mean follow-up of 6.8 years, SCD comprised 136 of the 254 cardiac deaths. The annual SCD event rate was 0.79% (95% confidence interval, 0.67-0.94). The following variables were independently associated with SCD in the multivariate model: myocardial infarction, heart failure, an estimated glomerular filtration rate of less than 40 mL/min/1.73 m(2), atrial fibrillation, physical inactivity, and diabetes. The incidences of SCD among women with 0 (n = 683), 1 (n = 1224), 2 (n = 610), and 3 plus (n = 246) risk factors at baseline were 0.3%, 0.5%, 1.2%, and 2.9% per year, respectively. The combination of clinical risk factors and LVEF (C-index, 0.681) were better predictors of SCD than LVEF alone (C-index, 0.600) and resulted in a net reclassification improvement of 0.20 (P < .001).

CONCLUSIONS

Sudden cardiac death comprised the majority of cardiac deaths among postmenopausal women with CAD. Independent predictors of SCD, including myocardial infarction, congestive heart failure, an estimated glomerular filtration rate of less than 40 mL/min/1.73 m(2), atrial fibrillation, physical inactivity, and diabetes, improved SCD prediction when they were considered in addition to LVEF.

Concentric left ventricular (LV) hypertrophy develops in response to a chronically increased LV afterload and is associated with increased cardiovascular events. Although the progression to systolic and diastolic heart failure is a known consequence of LV hypertrophy, few data are available on the frequency of deterioration to systolic dysfunction in patients with LV hypertrophy who originally had a normal LV ejection fraction. We evaluated the baseline and follow-up characteristics in 1,024 patients with concentric LV hypertrophy and a normal ejection fraction who had paired echocardiograms that were separated by ≥1 year. Systolic dysfunction occurred in 134 patients (13%) after a mean follow-up of 33 ± 24 months. The most common associated variable was interval myocardial infarction, which occurred in 43% of patients. Other risk factors for developing LV systolic dysfunction included QRS prolongation (>120 ms) and elevated follow-up arterial impedance defined as a value >4.0 mm Hg/ml/m(2). Patients with either a prolonged QRS interval or an elevated follow-up arterial impedance had twice the likelihood of developing LV systolic dysfunction, and, if both factors were present, there was a greater than fourfold increased risk of developing systolic dysfunction. Blood pressure measurements alone did not adequately reflect an elevated arterial impedance. In conclusion, 13% of patients with a normal ejection fraction and concentric LV hypertrophy progress to systolic dysfunction during approximately 3 years of follow-up. The risk factors for loss of function were interval myocardial infarction, prolonged QRS, and chronically elevated arterial impedance.