This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Atherosclerosis is a widespread disease affecting coronary arteries. Diffuse atherosclerotic disease affects the whole vessel, posing difficulties in determining lesion significance by angiography. Research has confirmed that revascularization guided by invasive coronary physiology indices improves patients' prognosis and quality of life. Serial lesions can be a diagnostic challenge because the measurement of functional stenosis significance using invasive physiology is influenced by a complex interplay of factors. The use of fractional flow reserve (FFR) pullback provides a trans-stenotic pressure gradient (ΔP) for each of the lesions. The strategy of treating the lesion with greater ΔP first and then reevaluating another lesion has been advocated. Similarly, non-hyperemic indices can be used to assess the contribution of each stenosis and predict the effect of lesion treatment on physiology indices. Pullback pressure gradient (PPG) integrates physiological variables of coronary pressure along the epicardial vessel and characteristics of discrete and diffuse coronary stenoses into a quantitative index that can be used to guide revascularization. We proposed an algorithm that integrates FFR pullbacks and calculates PPG to determine individual lesion importance and to guide intervention. Computer modeling of the coronaries and the use of non-invasive FFR measurement together with mathematical algorithms for fluid dynamics can make predictions of lesion significance in serial stenoses easier and provide practical solutions for treatment. All these strategies need to be validated before widespread clinical use.

BackgroundMyocardial ischemia is caused by epicardial coronary artery stenosis or atherosclerotic disease affecting microcirculation. Trimetazidine (TMZ), promotes glucose oxidation which optimizes cellular energy processes in ischemic conditions. Small studies demonstrated protective effects of TMZ in terms of reducing myocardial injury after percutaneous coronary intervention (PCI), its effect on microcirculation using contemporary investigative methods has not been studied. The aim of the study was to examine effects of trimetazidine, given before elective PCI, on microcirculation using invasively measured index of microcirculatory resistance (IMR).MethodsThis was prospective, single blinded, randomized study performed in a single university hospital. It included consecutive patients with an indication for PCI of a single, de novo, native coronary artery lesion. Patients were randomly assigned to receive either TMZ plus standard therapy (TMZ group) or just standard therapy. Coronary physiology indices fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were measured before and after PCI using coronary pressure wire.ResultsWe randomized 71 patients with similar clinical characteristics and risk profile, previous medications and coronary angiograms. Patientshad similar values of Pd/Pa, FFR and CFR prior to PCI procedure. After PCI, FFR values were higher in TMZ group, while IMR values were lower in this group respectively (FFR TMZ + 0.89 ± 0.05 vs. TMZ – 0.85 ± 0.06, p = 0.007; CFR TMZ + 2.1 ± 0.8 vs. TMZ- 2.3 ± 1.3, p = 0.469; IMR TMZ + 18 ± 9 vs. TMZ- 24 ± 12, p = 0.028). In two-way repeated measures ANOVA PCI was associated with change in FFR values (TMZ p = 0.050; PCI p < 0.001; p for interaction 0.577) and TMZ with change in IMR values (TMZ p = 0.034, PCI p = 0.129, p for interaction 0.344).ConclusionAdding trimetazidine on top of medical treatment prior to elective PCI reduces microvascular dysfunction by lowering postprocedural IMR values when compared to standard therapy alone.