Informatica

Coronary artery disease (CAD) is the most common type of heart disease and a major cause of death and disability in developed countries in both men and women (Roger, 2007). Most of the studies allow that the mortality has gradually declined and touches particularly advanced age population, but several reports have illustrated it still causes about one-third of all deaths in population over 35 years or sometimes earlier (Rosamond et al., 2008; Nichols et al., 2014). According to a report of AHA for people aged 40 years, the lifetime risk of developing CAD was 49% in men and 32% in women whereas for those reaching 70 years, the lifetime risk was 35% in men and 24% in women, respectively (Sanchis-Gomar et al., 2016). Goyal and Yusuf reported that CAD mortality was expected to increase by approximately 29% in women and 48% in men in developed countries between 1990 and 2020 (Goyal and Yusuf, 2006). The main specific reasons for such worsening epidemiologic situation are the rapid increase of globalization, urbanization, aging of society, growing rate of chronic and systemic diseases, closely associated with developing of CAD (Horton, 2015; Danaei et al., 2013).

CAD, which is often defined as silent ischemia, for some reason has increasingly become asymptomatic or atypically expressed which can lead to more serious manifestations such as MI or sudden death. As a rule, this category of patients does not fall into the view of cardiologists. Patients who show entirely expressed positive CAD symptoms routinely receive electrocardiograms, exercise tests, 24-hour ECG recordings, and standard echocardiography. In the case of positive main CAD tests, the invasive coronary artery angiography (CAA) procedure is recommended as a golden standard since it has a possibility to precisely verify or exclude CAD diagnosis. However, a real problem exists with patients who possess limited coronary artery damage (stenosis range <70%) and who are clinically quite problematic, but do not receive adequate and sufficient attention of clinicians. There are only a few papers on the importance and dynamics of clinical status of such a category as well as treatment strategy and its effectiveness control. In this regard, echocardiography could be the most common cardiac imaging technique for patients with suspected cardiac disease to assess cardiac function and status. But ordinary echocardiography at rest provides undervalued information in the presence of CAD in patients suspected of having stable angina pectoris (SAP) (Vanoverschelde and Goffinet, 2007).

We focused our attention on speckle tracking echocardiography (STE) as a non-invasive method that could be more informative for the assessment of global and regional left ventricular myocardial function. STE offers the opportunity to evaluate myocardial deformation independently of both cardiac translation and the insonation angle (Teske et al., 2007). Strain and strain rate (SR) describe the amount and rate of deformation of the myocardium throughout the cardiac cycle and it can be qualified as more sensitive descriptors of regional myocardial function comparing with conventional measures of myocardial function. Therefore, our study aimed to evaluate patients with limited state of changes in coronary arteries detected by CAA, discard the dynamics of these changes over the 2 years, identify the relevant diagnostic criteria and assess the efficacy of applied treatment by using STE method.

SAP has become a significant medical problem within the community, although it receives less attention in general cardiology practice. The principal objectives in the management of SAP to both acute and chronic forms mainly include the prevention of great cardiac events and the improvement of health status (Beltrame, 2017). Clinically, SAP patients have three key components: angina symptoms, various functional limitations, and poor health quality, and each of these components is directly related to MI or mortality, therefore the importance of evaluating these patients is obvious, especially considering the chronic nature of the disease (Beltrame, 2017). In this regard, LVEF is the most commonly used echocardiographic parameter to assess cardiac function and status in cardiology, where it is essential to guide therapy and for prognostication (Yeboah et al., 2016). Still, echocardiography as a “gold standard” image modality is recommended for assessment of patients in SAP, but it has limitations including high inter- and intra-observer variability. In our study, both control and CAD group patients had LVEF ⩾60%, so according to the value judgment, whey were “clinically normal”. But in the study, over 80% of both group patients had some symptoms of myocardial ischemia. Looking from the clinical perspective, STE has already been used for assessing ischemia-related myocardial and systemic diseases, where it can predict probable subclinical cardiac disorder earlier in the course of the disease, when conventional 2D echocardiography appears to be normal (Aggeli et al., 2015). STE should provide more information on the rate of segmental and global myocardial deformation such as factors for early cardiac pathology detection, herewith this method has been systematically validated to sonomicrometry, tagged MRI and colour-coded tissue Doppler echocardiography (Vanoverschelde and Goffinet, 2007; Amundsen et al., 2006).

GLS is useful for detecting both significant and limitary (⩽70%) coronary artery stenosis during stress tests even at rest (Rosamond et al., 2008; Biering-Sørensen et al., 2014). It provides an insight into the longitudinal, circumferential, and radial mechanics of the heart and valuable insights to myocardial deformation by quantifying strain and torsion with the inherent advantage of being angle-independent (Nesbitt et al., 2009; Huang and Orde, 2013). According to Biering-Sorensen, GLS can identify which concrete coronary artery suffers from significant stenosis. GLS was significantly lower in patients with CAD compared to patients without CAD and remained an independent predictor of CAD after multivariable adjustment for baseline data, exercise ECG and conventional echocardiographic parameters (Biering-Sørensen et al., 2013). Interestingly, longitudinally orientated myocardial fibres are located on subendocardial layers, the area most susceptible to ischemia, that is why measurements of longitudinal motion and deformation may be the most sensitive markers of CAD using tissue Doppler imaging (TDI) or 2-dimensional strain echocardiography (2DSE) (Biering-Sørensen et al., 2014; Hoffmann et al., 2012). We found an improvement of parameters in GLS longitudinal strain (LAD and LCX) on CAD and GLS circumferential strain in control groups, respectively. The vast majority of studies show the benefits of STE in identifying early CAD features when the results of other studies are uncertain. In opposite, the main findings of our study demonstrate that STE at rest is not suitable for the evaluation of the hemodynamical significance of coronary artery stenosis which is smaller than 70%. During an observation period of 2 years, we detected an improvement of measured parameters of STE. It means that the clinical condition of our patients over the two years has improved in both control and CAD groups. We, therefore, speculate that microvascular angina (MVA) may be responsible for this. Many patients at the initial stage of SAP and evidence of myocardial ischemia do not have a detectable or significant range of coronary atherosclerosis at CAA. Primary stable MVA defines patients with SAP, positive stress test results, and angiographically normal coronary arteries (Montalescot et al., 2013). The origin of MVA leading to functional abnormalities of coronary resistive vessels is not yet determined because of the heterogeneous entity and multiple pathophysiological mechanisms. Depending on the pathogenetic mechanism, there are 4 types of clinical classification of coronary microvascular dysfunction (CMD) according to the original classification proposed by Camici and Crea (Camici and Crea, 2007). Standardized diagnostic clinical criteria for evaluation of MVA are as follows: (1) symptoms of myocardial ischemia, (2) absence of obstructive CAD (<50% diameter reduction or FFR > 0.80), (3) objective evidence of myocardial ischemia and (4) evidence of impaired coronary microvascular function (Ong et al., 2018). Definitively, MVA is diagnosed if all four criteria are present. Suspected MVA (sMVA) is diagnosed if symptoms of ischemia are present (criteria-1) with no obstructive coronary artery disease (criteria-2) but only objective evidence of myocardial ischemia (criteria-3), or evidence of impaired coronary microvascular function (criteria-4) alone, respectively (Ong et al., 2018). In our study, all patients both in control and CAD groups had evidence of three criteria mentioned above. These findings could be partially explained by the suitable treating of sMVA. Angina caused by coronary microvascular dysfunction in a sizeable proportion of patients undergoing CAA for anginal symptoms is found to show normal coronary arteries or nonobstructive CAD (stenosis <70%). For many years, there was uncertainty regarding the real significance of anginal symptoms that are accompanied by electrocardiographic evidence of ischemia during stress. In 1988, Cannon and Epstein demonstrated that compared with asymptomatic controls, in patients with chest pain and on CAA normal coronary arteries the coronary microcirculation has a heightened sensitivity to vasoconstrictor stimuli and a limited microvascular vasodilator capacity during atrial pacing which is allusive with the presence of MVA. The main goal of treatment of MVA is global risk factor control and anti-anginal treatment possibly targeting both large epicardial coronary arteries and coronary microcirculation (Crea et al., 2014). Common treatment mainly includes ACE inhibitors, statins, B-blockers, Ca channel blockers, antithrombotic, and nitrates. All our groups’ patients had this treatment during the two years (Table 1). In our opinion, this fact has led to an improvement of STE. Even though drugs can help alleviate symptoms, many patients still have refractory symptoms, and treatment of these patients remains challenging. Atherosclerosis of small coronary arteries and its’ caused MVD affects myocardial longitudinal strain. Our study has shown that measurements of longitudinal strain could be useful when evaluating dynamic of myocardial function in SAP with nonobstructive coronary arteries.

Patients with MVD had significantly impaired diastolic function compared with healthy individuals. Moreover, improvement in GLS (−18.88 ± 0.48% vs. −20.52 ± 0.57%; $p<0.006$; LAD) and (−17.9 ± 0.87% vs. −19.78 ± 0.86%; $p<0.049$; LCX) should be interpreted as a possible result of MVD successful therapeutical correction both in “healthy” control and CAD patients.

The main findings of our study demonstrate that STE is suitable for the evaluation of the hemodynamical and clinical significance of limitary nonobstructive coronary artery stenosis (less than 70%). STE should provide more information on the rate of segmental and global myocardial deformation such as factors for early selective cardiac pathology detection. Microvascular angina may be important for the health status of patients at the initial stage of SAP, since evidence of myocardial ischemia is not detectable in CAA. STE could be informative and effective for evaluation and adequate treatment of patients at different stages of CAD.

The limitations of this study are as follows. First, the main focus was not only to evaluate asymptomatic patients with limited changes in coronary arteries but to determine selective and typical findings of STE, which could be informative diagnostic and adequate treatment criteria meaning that it is simple, quick, and noninvasive. Second, the presence of MVA still must be confirmed by other examinations. Third, relatively small number of patients were enrolled. Nonetheless, we will continue to do this research in the future, in particular by increasing the number of patients being examined and making a better patient selection.