Pursuing meaningful end-points for stem cell therapy assessment in ischemic cardiac disease

Abstract

Despite optimal interventional and medical therapy, ischemic heart disease is still an important cause of morbidity and mortality worldwide. Although not included in standard of care rehabilitation, stem cell therapy (SCT) could be a solution for prompting cardiac regeneration. Multiple studies have been published from the beginning of SCT until now, but overall no unanimous conclusion could be drawn in part due to the lack of appropriate end-points. In order to appreciate the impact of SCT, multiple markers from different categories should be considered: Structural, biological, functional, physiological, but also major adverse cardiac events or quality of life. Imaging end-points are among the most used - especially left ventricle ejection fraction (LVEF) measured through different methods. Other imaging parameters are infarct size, myocardial viability and perfusion. The impact of SCT on all of the aforementioned end-points is controversial and debatable. 2D-echocardiography is widely exploited, but new approaches such as tissue Doppler, strain/strain rate or 3D-echocardiography are more accurate, especially since the latter one is comparable with the MRI gold standard estimation of LVEF. Apart from the objective parameters, there are also patient-centered evaluations to reveal the benefits of SCT, such as quality of life and performance status, the most valuable from the patient point of view. Emerging parameters investigating molecular pathways such as non-coding RNAs or inflammation cytokines have a high potential as prognostic factors. Due to the disadvantages of current techniques, new imaging methods with labelled cells tracked along their lifetime seem promising, but until now only pre-clinical trials have been conducted in humans. Overall, SCT is characterized by high heterogeneity not only in preparation, administration and type of cells, but also in quantification of therapy effects.

Regenerative Medicine for the Treatment of Ischemic Heart Disease; Status and Future Perspectives

“…They are categorized into some groups, including structural, biological, functional, physiological, major adverse cardiac events (MACE), or quality of life. Structural endpoints contain different items that are (Dorobantu et al, 2017):…”

“…The next step in this field is to find an efficient way of assessing the pros and cons of cardiac cell therapy and recognize if it improves IHD or not. Different categories of strategies are available to evaluate the progression, by using equipment like magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission CT (SPECT) (Dorobantu et al, 2017).…”

Perspectives of cell therapy for myocardial infarction and heart failure based on cardiosphere cells

“…В то же время существенного улучшения ФВЛЖ по сравнению с контролем не обнаружено. Здесь необходимо отметить, что ФВЛЖ зависит от многих параметров, включающих нагрузку объемом, геометрию желудочков, характер электрической активации, и поэтому, возможно, не является наиболее подходящим суррогатным маркером для оценки эффективности клеточной терапии [82]. Необходимы новые более крупные исследования и более длительные наблюдения для оценки влияния этого метода лечения на смертность и сердечно-сосудистые осложнения.…”

Moving forward on the pathway of cell-based therapies in ischemic heart disease and heart failure – time for new recommendations?

“…Since the first in-man SCT for IHD[3], a substantial number of clinical trials (CTs) have been finalized and comprehensive reviews and meta-analyzes have been published, yielding inconsistent results[4,5]. But when it comes to papers expressing opinion and recommendations from expert authorities, their number is not so impressive.…”