Prediction of improvement in cardiac function by high dose dobutamine stress echocardiography in patients with recent onset idiopathic dilated cardiomyopathy

Abstract

The prognosis of patients with recent onset idiopathic dilated cardiomyopathy (DCM) is grave and highly variable [1]. Dobutamine stress echocardiography (DSE) has been used to assess contractile reserve in patients with ischemic and idiopathic DCM. Several studies have suggested that contractile reserve assessed by DSE can be of prognostic value inpatientswith idiopathic DCM [2–5]. In this study,we investigated whether contractile reserve on DSE could predict late improvement of cardiac function and had incremental prognostic value for future cardiac events in recent onset idiopathic DCM. Between December 2004 and May 2011, forty-one patients were enrolled in this study. The study population consisted of patients with idiopathic DCMwho had symptom durations of less than 6 months. All study subjects underwent coronary angiography to exclude ischemic heart disease, and endomyocardial biopsies were performed in 35 patients (85%) to exclude reversible causes, such as myocarditis. Patients with chronic kidney disease (estimated glomerular filtration rate b60 ml/min/1.73 m) were also excluded. All patients had a complete echocardiographic study and follow-up echocardiogram was performed after 6 month and 12 month, then when any clinical events occurred. The interval between the time of DSE and last follow-up echocardiogramwas 16±15 months. Dobutamine was infused in 5-min dose increments, starting from 5 μg/kg/min and increasing to 10, 20, 30, and finally, to the maximal dose of 40 μg/kg/min. The infusion was discontinued before the maximal dose was reached if 85% of the maximal predicted heart rate for the age group was achieved, or if symptomatic complex ventricular arrhythmias, defined as the presence of multiform or repetitive ventricular extrasystoles, were observed. Beta-blockers were stopped 48 h before dobutamine testing in all patients taking these agents. The institutional committee of Kyungpook National University Hospital approved the study protocol. Informed consent was obtained in all patients. Cardiac death and hospitalization were combined end-point. The mean age of the patients was 50±14.8 years, and 24 patients (59%)weremale. During themean follow-up period of 30±24 months, 14 patients (34%) experienced cardiac events, and 5 (12%) of them died. Three (7%) of themwere sudden cardiac death, and two (4%) were low cardiac output death. Of the remaining patients, 9 (21%) were rehospitalized due to aggravation of heart failure. During dobutamine infusion, no significant complications occurred. Tenpatientsdidnot reachapeakdoseof dobutamine. Sixpatients reached maximal heart rates before thepeakdose of dobutamine, and in 4patients the test was stopped before the peak dose due to frequent premature complex. The mean value of the maximal dobutamine dose given was 35.6±8.7 μg/kg/min. We investigated the correlation between follow-up LVEFand clinical and echocardiographic parameters (Table 1). The followup LVEF correlated with baseline LVEDV (r=−0.519, p=0.001), LVESV (r=−0.499, p=0.001), LVEDV at peak dose (r=−0.509, p=0.001), LVEFat peakdose (r=0.692, pb0.001), and the changeof LVEF (r=0.515, p=0.001) from baseline to peak dose of dobutamine. Among them, LVEF at the peak dose of dobutamine was the most significant predictor of follow-up LVEF. Follow-up LVEFwas predicted by LVEF at the peak dose of DSE (y=1.033×−0.979, r=0.465, p=0.001). Receiver-operating characteristic analysis was used to determine the optimal cutoff value for predicting cardiac events with respect to the change of LVEF. The optimal change in LVEFwas 9.8%, The Kaplan–Meier survival estimates were stratified according to the results of baseline to peak LVEF variation during dobutamine administration (Fig. 1). The presence of inotropic response after dobutamine infusion, identified in this study as a change of LVEF≥9.8%, showed a significantly better outcome than little inotropic response (pb0.001). In the Cox-proportional hazard model, the change of LVEF from peak to baseline (hazard ratio [HR] 0.834, 95% confidence interval [CI] 0.713–0.976, p=0.024), in addition to age (HR 0.921, 95% CI 0.863– 0.984, p=0.015), log NT-ProBNP (HR 0.261, 95% CI 0.091–0.749, p=0.013), deceleration time (HR 0.964, 95% CI 0.932–0.998, p=0.039) and E/E′ ratio (HR 1.177, 95% CI 1.046–1.325, p=0.007) was also a significant independent predictor of cardiac event (Table 2). Moreover, the LVEF change in DSE had incremental prognostic value to