Myocardial Layer‐Specific Longitudinal Strain for Identification of the Culprit Vessel in Elderly Patients With NSTE‐ACS

Volume regulation graph (VRG) for 3 data sets (squares) referring to different degrees of coronary stenosis. Associated averaged data for patient cohorts are identified and presented: no significant stenosis, significant stenosis and occlusion. The corresponding data for group average end-systolic volume (ESV) and end-diastolic volume (EDV) are shown, and they appear in ascending order. As average ESV and EDV seem to increase in a pari passu fashion (green line and regression equation), their ratio (reflected by ejection fraction, EF) does not appreciably vary. Maximum EF is indicated by the red line, and minimum EF by the blue line, without significant difference. Based on published data. Also presented are average data for various other studies that employ territorial longitudinal strain (TLS) to detect a culprit vessel. Inset (green color): survey of various metrics used to evaluate severity of a coronary stenosis or detection of culprit vessel, including percentage arterial diameter reduction (% D), left ventricular EF (LVEF), fractional flow reserve (FFR), global longitudinal strain (GLS), TLS, and wall motion score index (WMSI). Providing clinicians with early information on culprit vessel (CV) identification aims to assist treatment decision making, but remains a challenging enterprise. This concern particularly applies to the non-ST-segment elevation acute coronary syndrome (NSTE-ACS), frequently encountered in elderly patients who often present with comorbidities and multivessel disease (MVD). These patients commonly show atypical symptoms and nonspecific abnormalities of the electrocardiogram (ECG). Rigorous clinical assessments, partly based on imaging modalities, are essential for guiding personalized treatment decisions in these frailty individuals [1]. It seems appropriate to start defining the specific age range when addressing issues around these older persons. Various options are in vogue, often based on the highly variable choice associated with retirement guidelines, as enforced at a national level. Alternatively, Subdivisions for Research and Health consider Young-Old (ages 65 to 74, often being healthier and more active individuals), Middle-Old (ages 75 to 84) and Oldest-Old (ages > 85 years, referring to a group with significantly higher healthcare needs) [2]. Before considering coronary angiography (CAG), various technical approaches are available to locate a stenosis when investigating the complex type of patients characterized above. These options include the ECG, analysis based on ejection fraction (EF), wall motion score index (WMSI) using conventional transthoracic echocardiography (TTE), or analyzing territorial longitudinal strain (TLS) obtained by speckle-tracking echocardiography (STE), also denoted as regional longitudinal strain (RLS) [3] or layer-specific longitudinal strain (LLS) [4]. Each myocardial layer has different inherent vulnerabilities to ischemia, and the endocardial layer is reported to be affected first by flow-limiting coronary stenosis [3]. Sarvari and colleagues were the first to explore a comparison of EF, WMSI and TLS in a prospective study concerning NSTE-ACS patients. They found that assessment of endocardial and mid-myocardial layer-specific strain echocardiography provided higher accuracy than did epicardial strain, WMSI, and EF [5]. In this issue of Echocardiography the comparison was extended to also include ECG changes, while specifically concentrating on elderly patients when identifying the CV in a noninvasive manner, notably also in MVD [6]. As the lesion at the site of the CV primarily causes a localized contraction abnormality, it is evident that compartmental measures such as end-diastolic volume (EDV) and end-systolic volume (ESV) may only be minimally affected. Consequently, the ratio of ESV and EDV, which is by definition the only determinant of ejection fraction (EF), likely remains fairly unaltered, or only shows a slight decrease associated with slightly increased ESV values. The schematic Figure 1A presents the nonlinear decreasing pattern of EF for increasing ESV, based on the mean value for stroke volume (SV) ± 1 standard deviation (SD) as reported by the study discussed here [6]. As the ventricle maintains cardiac output, the nearly constant stroke volume will increase EDV, making that the combined effect of elevated ESV and EDV is largely cancelled out in the ratio EF. This interpretation is confirmed by the patient data presented in the publication by Sarvari et al. [5], as documented in the Graphical Abstract. Indeed, EDV follows ESV in a pari passu fashion. Adaptation in action here yields a linear relationship for scenarios of “no stenosis”, “significant stenosis” and “occlusion,” respectively. Meanwhile, the corresponding values for EF do not change significantly. Being a metric without physical units, the utility of EF has therefore been questioned [7]. Inspection of additional findings reported in similar studies as conducted by Sun et al. [6] are also included in the Graphical Abstract, and confirm that their average data points are centered in the same region of the volume domain representation. Thus, CV-related issues primarily need to be investigated locally, rather than at the compartmental level. The next question now to answer is: how to detect the location of the CV, especially in cases of MVD? Various approaches have been applied to assess severity of a coronary stenosis. The traditional route determines percent diameter stenosis (% D), originally using angiography, and nowadays applying more advanced imaging techniques. Later, WMSI, GLS and TLS were introduced, besides an invasive procedure based on paired arterial pressure measurements, used to calculate fractional flow reserve (FFR), commonly accepted as the gold standard, but otherwise again a dimensionless ratio [8, 9]. STE enables quantitative, noninvasive analysis of multidirectional myocardial deformation, potentially providing an attractive approach for preoperative CV identification. While applying well-specified exclusion criteria, their retrospective study aimed to evaluate the CV detection capability of ECG, WMSI, and TLS as based on STE in 142 NSTE-ACS patients (age 67±13, 30% < 60 years, 74% male) [6]. The findings were compared with subsequent angiographic studies performed in their patients, and used to independently assess the CV based on CAG results. Comorbidities listed include hypertension (70%), diabetes (42%), and dyslipidemia (54%), while smoking (48%) was indicated as risk factor. Remarkably, renal involvement was not reported, although chronic kidney disease belongs to one of the four most frequently mentioned chronic disorders observed in the elderly [1]. Specificity and sensitivity of diagnostic performance for the three approaches were evaluated and compared for left circumflex artery (LAD), right coronary artery (RCA) and left circumflex artery (LCX). Detailed results are clearly presented in their tables and figures, as well as in the supplementary file. In particular the epi-TLS not only effectively differentiated myocardial function across coronary territories with varying stenosis severities, but also served as an independent predictor of CV in multivariate regression analysis. Various statistical models were explored, and in single vessel disease, the WMSI+TLS model outperformed WMSI alone. In cases of MVD the epi-TLS independently predicted the CV and surpassed other myocardial layers in diagnostic performance. The authors conclude that STE offers a practical bedside evaluation for NSTE-ACS patients before undergoing invasive procedures. Investigations employing FFR concentrate on occlusions of major coronary arteries, while the metric coronary flow reserve explores the degree of coronary microvascular dysfunction [12]. Only very few studies also determined FFR when exploring the performance of TLS in NSTE-ACS patients. Remarkable exceptions include publications considering that the endocardial layer is more vulnerable to ischemia than the epicardial layer. This notion follows from the observation that the endocardial layer has greater oxygen consumption compared with the epicardial layer when coronary perfusion is normal, and it receives less collateral flow when perfusion is compromised. For coronaries with ≥50% stenosis, the regional whole-layer and endocardial longitudinal strain (LS) were significantly smaller in segments perfused by vessels with an (abnormal) FFR < 0.75 than in those with an FFR ≥ 0.75, but epicardial LS was not [11]. Figure 1B shows data for patients with FFR < 0.75, along with their ESV and EDV values [9], documenting that abnormal FFR-values are not associated with EF. Notably, a “preserved” EF (i.e., >50%) is no indication for absence of significant coronary artery disease. Perhaps even more important is the observation that a normal EF does not necessarily mean the combined presence of normal ESV and normal EDV. In fact, normality of ventricular volume is sex-specific, and only corresponds with a very limited territory within the “preserved” EF domain. Interestingly, data [5] shown in the Graphical Abstract suggests that stenosis severity is associated with ventricular size. Interestingly, the findings presented also fuel the unresolved discussion on the superiority of epi-TLS [6] versus endo-TLS [5, 11, 13], while appreciating that NSTE-ACS patients form a heterogeneous group [3]. Briefly, the authors provide several explanations: (1) the superior speckle-tracking performance in the epicardial region; (2) nonuniform distribution of myocardial strain values across layers and regions: compared to endocardial strain, epicardial strain exhibits smaller variations from base to apex; (3) superior reproducibility of the epicardial layer [6]. Myocardial strain is known to be age- and sex-dependent [14], while additionally several risk factors such as type 2 diabetes or arterial hypertension may affect layer-specific deformation of the left ventricle [15]. Nevertheless, the TLS-method as documented by Sun et al. [6] appears to meet the goal of noninvasively and accurately identifying the culprit vessel in NSTE-ACS, at least in the age group investigated in their study [6]. Besides considering truly oldest-old patients [16], future research should also focus on sex-specific aspects, as well as possible interference by other components—often associated with comorbidities—that may impact the interpretation of myocardial strain measurements [17, 18].