Cardiac sympathetic innervation, assessed with 123I-MIBG SPECT, predicts left ventricular function improvement in patients with newly diagnosed dilated cardiomyopathy

Abstract

Abstract Introduction Beta-blockers (BB) are commonly prescribed medications for heart failure (HF) due to their ability to counteract the increased sympathetic nervous system (SNS) activity seen in HF, resulting in downregulation and desensitization of β-receptors. In patients with dilated cardiomyopathy (DCM), the introduction of BB therapy can lead to left ventricular ejection fraction (LVEF) improvement in 30-50% of cases. Single-photon emission computed tomography (SPECT) with 123I-meta-iodobenzylguanidine (MIBG) is a useful tool for assessing cardiac SNS activity. Healthy individuals typically exhibit high SPECT-MIBG uptake and low washout rate (WR) due to normal β-receptor levels and low norepinephrine (NE) levels, respectively (Fig 1A). While better SPECT-MIBG results have been associated with LVEF improvement in the general HF population, less data is available for DCM patients. Purpose This study aimed to evaluate the predictive value of MIBG-SPECT for LVEF improvement in newly diagnosed DCM patients. Methods Twenty-one DCM patients (mean age 47 ± 10 years, 90% male, baseline LVEF 29.5 ± 8.7%, left ventricular end-diastolic volume (LVEDV) 114 ± 36 ml/m2) with stable HF symptoms (NYHA class 1.8 ± 0.6) and newly diagnosed DCM underwent baseline MIBG-SPECT and echocardiography. HF therapy was initiated and up-titrated, and echocardiography was repeated at 6 months. Semi-quantitative parameters from MIBG-SPECT, including the MIBG uptake ratio from the heart and mediastinum (H/M) at 15 minutes (-15) and 4 hours (-4), as well as the WR [WR = (H/M-15 - H/M-4) / H/M-15], were evaluated. Patients were stratified based on median WR - 8.79 (IQR 5.17-12.90). Results After 6-months of HF therapy up-titration, 18 patients improved LVEF, and the mean LVEF increase was 7.7 ± 10.4%. Although, patients with WR > median did not differ in terms of baseline LVEF (30.2 ± 7.0 vs. 27.7 ± 9.6, p=0.52), they had worse LVEF at 6 months (32.0 ± 11.0 vs. 40.6 ± 9.2%, p=0.04). Moreover, WR at baseline strongly correlated with 6-month LVEF (R=-0.51, p=0.01) and was a significant predictor of 6-month LVEF (β=-0.55 ± 0.19, p=0.009). Moreover, WR could successfully predict LVEF improvement ≥ 10% (OR 1.27 [95%CI 1.01-1.61], p=0.03; AUC 0.82 [95%CI 0.63-0.99], p<0.001) with a cut-off point of 8.0 (sensitivity 88%, specificity 77%) (Fig 1B). Conclusion Most DCM patients demonstrated LVEF improvement during 6 months of HF therapy up-titration. Baseline WR from MIBG-SPECT was found to be a reliable predictor of significant LVEF improvement in this patient population.Fig1.A-SPECT-MIBG results. B-ROC curve.