Is There an Incremental Prognostic Value of Evaluating Left Ventricular Dyssynchrony by Gated SPECT in Patients with Systolic Heart Failure and Altered Myocardial Sympathetic Innervation as Evaluated by Cardiac I-123 mIBG Imaging?

Background: Altered myocardial sympathetic innervation activity (AMSI) is known to be present in systolic heart failure patients (SHF) and recently SPECT imaging using I-123 mIBG heart to mediastinum (H/M) ratio <1.6 has been shown to predict MACE in the ADMIRE-HF trial. Left ventricular mechanical dyssynchrony (LVMD) is known to be present in a substantial number of SHF patients and has been studied mainly to guide CRT therapy. Recently gated SPECT has shown promise to provide an accurate assessment of LVMD. It remains unclear how the combination of AMSI and LVMD collectively affect clinical outcomes and other cardiovascular parameters. Objectives: The objectives are to examine the clinical characteristics and incremental prognostic value for MACE of LVMD determined by SPECT in SHF patients with or without abnormal cardiac MIBG uptake (H/M ratio < 1.6). Methods: Out of 30 SHF patients who participated from our institution in the ADMIRE-HF trial studying MIBG based AMSI, we included 22 patients with abnormal MIBG H/M ratio of <1.6. We performed gated SPECT LVMD analysis on these patients using the Emory Cardiac Toolbox. The 2 SPECT variables for LVMD assessed were histogram bandwidth and phase standard deviation both of which assess the extent of dispersion of LV activation during contraction as a marker of LVMD. Patients were followed up for a mean period of 6 years. The primary end point was mortality from any cause and secondary end point was heart failure admission or myocardial infarction or ICD shock. Results: 2 Groups were defined: Group A: n = 17 with H/M MIBG ratio < 1.6 and +LVMD and Group B, n = 5 H/M MIBG ratio &minus;LVMD. Baseline characteristics, cardiac risk factors and medications were comparable between both groups. LVEF was lower and RBBB was less common in Group A. There was no statistical difference in achievement of primary or secondary end points in the two groups including death heart failure readmissions, ICD shocks or MI. Conclusions: In our pilot study, we did not find definitive value of adding SPECT based LVMD to abnormal cardiac MIBG imaging in SHF patients with regards to predicting outcomes. Although our sample size is too small to make any definitive conclusions, it is possible that LVMD works independently through different pathways in the progression of SHF and hence may not necessarily add incremental value to AMSI determination using MIBG.

Aliskiren ameliorates sympathetic nerve sprouting and suppresses the inducibility of ventricular tachyarrhythmia in postinfarcted rat heart

Background Aliskiren is an oral renin inhibitor, which inhibits the first rate limiting step in the renin angiotensin aldosterone system. In this study, sympathetic nerve sprouting and the inducibility of ventricular fibrillation after aliskiren treatment in myocardial infarction were investigated. Methods Male Sprague Dawley rats after coronary artery ligation were randomly allocated to four groups： angiotensin converting enzyme inhibitor enalapril, angiotensin receptor blocker valsartan, 13 adrenergic receptor blocker carvedilol and rennin inhibitor aliskiren treatment for six weeks. Electrophysiological study, histological examination and Western blotting were performed. Results The plasma norepinephrine level and sympathetic nerve innervation significantly increased in treated infarcted rats compared to untreated rats. Aliskiren treatment reduced the sympathetic nerve innervations after myocardial infarction. There is no significant difference in sympathetic nerve innervations after myocardial infarction among the enalapril, valsartan, carvediloand or aliskiren treated groups. Programmed electrical stimulation study showed that inducible ventricular arrhythmia was reduced, ventricular fibrillation threshold was increased and ventricular effective refractory period was prolonged in enalapril, valsartan, carvedilol and aliskiren treated infarcted rats compared to untreated infarcted rats. Cardiomyocytic apoptosis in infarcted region was significantly decreased in enalapril, valsartan, carvedilol and aliskiren treated infarcted rats. Conclusions Aliskiren ameliorated cardiomyocytic apoptosis, attenuated the sympathetic nerve innervations and reduced the vulnerability of ventricular arrhythmias after myocardial infarction. Enalapril, valsartan and carvedilol have similar effects as aliskiren on cardiomyocytic apoptosis, sympathetic nerve innervations and vulnerability of ventricular arrhythmias after myocardial infarction.