Gated ${}^{99m}$Tc-tetrofosmin SPECT and gated ${}^{18}$F-FDG PET for the assessment of left ventricular myocardial dyssynchrony and its impact of the left ventricular function. A functional imaging study

Globally, cardiovascular disease (CVD) is the leading cause of mortality. Coronary artery disease (CAD) is one of the most prevalent types of CVD and annually accounts for around half of all CVD deaths. Therefore, CAD is one of the main contributors to massive health, and health-economic, burdens. A major factor in the morbidity and mortality of CAD is Left Ventricular Mechanical Dyssynchrony (LVMD). LVMD can also be used as a measure of disease burden, and thus also determines the further course of treatment.Currently, the non-invasive standard test within nuclear medicine diagnostic imaging for patients with CAD is ECG-gated myocardial perfusion scintigraphy (MPS). Another well-recognized non-invasive imaging technique for myocardial metabolic imaging (MMI) is ECG-gated ${}^{18}$Ffluorodeoxyglucose PET (FDG-PET). Several computer software packages are currently available to provide phase analysis of ECG-gated MPS imaging and also ECG-gated FDG PET for the evaluation of LVMD. For our analyses we used Quantitative Gated SPECT (QGS, Cedars-Sinai, Los Angeles, California). Phase analysis of LVMD in patients with heart failure (HF) provides an additional tool to select patients for cardiac resynchronization therapy (CRT). The results of LVMD phase analysis of MPS and FDG-PET leads to a better selection of patients for CRT improving both treatment efficacy and cost efficiency. In our joint publication we investigated the performance of gated FDG PET phase analysis as compared to gated MPS as well as looked at possible cut-off values for FDG PET to define dyssynchrony. We analyzed the phase analysis parameters Bandwidth (BW), Phase Standard Deviation (Phase SD), and Entropy between SPECT and PET datasets. Based on the results we could only find moderate agreement between SPECT and PET to identify dyssynchrony. Entropy was the best single PET parameter to predict dyssynchrony. The optimized cut-off value for Entropy was 63%. In my first author publication we further investigated the relationship between LVMD and LV function. We were able to show that LVMD is linked to significantly higher end diastolic volume (EDV) and end systolic volume (ESV) as well as a significantly reduced left ventricular ejection fraction (LVEF) for MPS and gated FDG PET imaging. Additionally, we validated that the increasing severity of LVMD is associated with increasing EDV and ESV as well as a decreasing LVEF. The association was strongest for the dyssynchrony parameter Entropy. Both studies show that phase analysis results of QGS for gated MPS and gated FDG-PET not only assess LVMD but also demonstrate a good correlation with LV function. Furthermore, we demonstrated that the methods cannot be used interchangeably, even though in principle both measure the same parameters. Establishing reference ranges and cut-off values is difficult due to the lack of an external gold standard. There is, however, limitation for both studies. Neverteless, this novel approach of objective analysis of dyssynchrony, is a great way forward to dive deeper into the phase analysis of both imaging techniques and thus to expand the clinical efficiency of these methods.