In the current study, we demonstrated that in patients with angiographically normal coronary arteries, long LAD that wrapped around LV apex ensured better longitudinal relaxation during late diastole, higher circumferential deformation at the LV apex, and augmented apical rotational mechanics. This deformational changes were resulting in higher LV twist despite no difference in LV ejection fraction measured by conventional methods. Longitudinal deformation in late diastole and LV apical rotation are independent predictors of LAD wrapping around LV apex in the presence of normal coronary circulation.
The present study is the first study, up to our knowledge, that investigated the relationship between LAD coronary artery anatomical features and cardiac mechanics in patients with angiographically normal coronary arteries.
Evaluation of LV function using 2D Echo-Doppler primarily is unable to describe detailed information about cardiac mechanics, specifically when there are no coronary arterial or structural heart diseases. Strain imaging using VVI is a semi-automated technique that is more precise and accurate in characterizing LV function than the conventional methods.
Additionally, as distinct from previous studies, in our study, measurements of longitudinal and circumferential strain incorporated specifically the mid myocardial layer which reflecting the true regional function allowing an early detection of subtle myocardial abnormalities [18, 19].
Lately published researches verified the crucial value of global longitudinal strain (GLS) as an important functional parameter that provides imperative diagnostic and prognostic information in patients presented with acute coronary syndromes [21, 22], and it has also been demonstrated as an independent predictor of significant CAD in patients with chronic stable angina [23]. Liou et al. [24] stated that GLS might be an initial marker of CAD in symptomatic patients. Furthermore, Stankovic et al. [25] claimed that 2D strain imaging was an exceptional choice to detect LAD stenosis especially in an acute setting. In parallel with these studies, the present study verified increased circumferential strain during diastole can predict the length of LAD and its wrapping around the LV apex in absence of LAD stenosis.
Kobayashi et al. [9, 10] investigated the association between anatomic features of LAD and patient’s outcome when presented with anterior ST-segment elevation myocardial infarction. They studied patients presented to CCU within 12 h after the development of suggestive symptoms of STEMI and subjected to primary percutaneous coronary intervention. Patients with LAD lesions confirmed to be the culprit lesions were divided into two groups, according to LAD anatomical features, as group 1: LAD wrapping (n = 871) and group 2: LAD non-wrapping (n = 224). They demonstrated that heart failure, significant arrhythmias, and LV mural thrombi were more common in the wrap-around LAD group. Additionally, LV ejection fraction was worse in the wrap-around LAD group (54.5% versus 58.7%, P < 0.006). Thereafter 3 years of follow-up, major adverse cardiac events (death, stroke/stent thrombosis) were higher (12.7% versus 5.4%, P < 0.002); death (6.6% versus 3.2%, P < 0.05), stroke (1.9% versus 0.5%, P < 0.12), stent thrombosis (5.6% vs 2.3%, P = 0.047), and severe heart failure (4.5% versus 1.4%, P < 0.03) were more prevalent in wrap-around LAD versus non-wrap-around LAD. Multivariate regression analysis revealed that LAD wrapping independently and considerably anticipated the occurrence of adverse cardiovascular events and severe heart failure in patients with an anterior STEMI.
In the current study, we perceived the explanation of different patient outcomes when LAD obstruction, with wrap-around apex, coexist as there is more loss of augmented function especially at LV apex; the LAD wrapping group had better mechanics and higher longitudinal relaxation. In addition, the main difference between wrapping and non-wrapping LAD groups is the higher circumferential function and augmented apical rotation that result in increased LV twist. So, not only a larger area of myocardium becomes vulnerable but a significant mechanical dysfunction is added when LAD obstruction supervenes, if LAD wraps around the apex.
Patients with proximal LAD occlusion are recognized by cardiac surgeons and cardiologists as a high-risk group with increased morbidity and mortality. However, not all proximal LAD lesions are of the same clinical relevance. Forty percent of LV myocardium is supplied by LAD, including the anterior wall and the anterior segment of the interventricular septum [26]. The LAD supplies all of this area, and much more when it wraps around the apex [3,4,5]. Therefore, according to our study, it is easy to understand now why proximal LAD disease can be a high-risk lesion. If LAD wrapping around the apex undergoes severe obstruction, not only a larger area of jeopardized myocardium is a consequence but also a loss of augmented LV function especially the apical rotational mechanics and the resulting LV twist.
During systole, the LV undergoes a unique twist motion with a counterclockwise rotation at the apex and a clockwise rotation at the base. The resulting twist during peak systole is 7.7 ± 3.5° [27]. This is followed immediately by rapid untwist at the end of the systole. This unique LV twisting is considered to be an important playing role not only in systolic but also in the diastolic function. LV twist generates positive torsional deformation forces that develop in the subepicardium layer that can be added to the opposing negative torsional motion originating in the subendocardium [27]. Eventually, the torque in the subepicardium impacts subendocardial deformation and the whole wringing motion of the heart will be affected with the reduction of rotational mechanics.
In our study, LV apical rotation and overall LV twist are much lower in LAD non-wrapping, and the larger part of LV twist is generated from apical counterclockwise rotation, so the peak LV twist is predominantly reduced in apical myocardial infarction; this might explain the reduction of LV torsion and even the occurrence of an apical aneurysm in apical myocardial infarction [28, 29].
Yet, in the present study, longitudinal strain did not differ between the study groups, and the longitudinal strain caused by the contraction of myocardial tissue in the endocardial layer and has a high sensitivity to myocardial ischemia which does not exist in our patients with angiographically normal coronaries. Several studies demonstrated that global longitudinal strain is a more sensitive and robust parameter for evaluating myocardial function compared to circumferential and radial strain [30, 31], while in normal myocardium, the circumferential strain is better reflecting both systolic and diastolic function [30, 31].
In addition, our study demonstrated that the left ventricular diastolic function as measured by deceleration time, longitudinal and circumferential strain, and strain rate during diastole (SRa and SRe) was enhanced in a patient with long LAD that wraps around the apex. The underlying mechanism was reported in Wang et al.’s research [32]. Myocardial perfusion occurs mostly in diastole because systolic contraction transiently prevents coronary blood flow, especially to the subendocardium. So vascular turgor and large blood supply especially, to cardiac apex, will better perfuse the normal myocardium and predominantly augment the diastolic function. This diastolic function is initially affected if coronary artery stenosis develops.
Our study is the first to address the relationship between LAD length and LV function. We found that long LADs (i.e., those in which the vessel wraps around the apex) had higher values of LV function especially during diastole. From previous studies, LAD has a major impact on prognosis in patients undergoing primary PCI. This is probably as a result of a greater amount of the muscle supplied by this type of LAD, and therefore, a greater amount of myocardial necrosis when the vessel totally occludes [9, 10]. Furthermore, the augmented LV function associated with LAD will be regained after revascularization. This claim is further strengthened in previous studies when no differences were found between the LAD wrapping and LAD non-wrapping groups with regard to the presence and extent of collaterals and the blush grade (reflecting myocardial perfusion) in patients after LAD revascularization, and LAD length was the main determinant after intervention [8, 33].
Notably, our study showed a strong positive correlation between the LV twist and longitudinal and circumferential strain and strain rate especially at LV apex, and this explains the augmented LV twist in the LAD wrapping group was associated with better circumferential strain values compared to the LAD non-wrapping group. We could expect that proximal LAD stenosis in such a group with LAD wrapping to further deteriorate LV function to a greater extent and recommend utilization of longitudinal and circumferential strain as an early marker of LAD stenosis that better reflect LV dysfunction than LV EF%. This is in agreement with Stokke et al. [34] who reported a study showing strain imaging probably better reflects systolic function in patients with a preserved estimated LVEF.
There are numerous factors such as age, sex, diabetes mellitus, and hypertension that can affect cardiac mechanics in our study population, as examined by longitudinal and circumferential strain. Tadic et al. [35] demonstrated that patients with non-complicated diabetes and hypertension also had impaired LV longitudinal strain. In the present study, the prevalence of hypertension was higher in the LAD wrapping group while diabetes mellitus and smoking were more prevalent in LAD non-wrapping group which makes both groups at equal risk. Moreover, the ratio of male to female patients was similar in the study population, so the role of these risk factors on cardiac mechanics cannot be used to explain the difference in cardiac mechanics.
We included a real-life patient’s population with a variable risk profile who was referred to the catheterization laboratory for coronary angiography. However, we thought that the impact of these risk factors on cardiac mechanics might be equivalent. In the LAD wrapping group, hypertension was prevalent in 60% while diabetes mellitus and smoking were prevalent in 100% and 46% in LAD non-wrapping which represents a balanced exposure to cardiovascular risk. Compensatory left ventricular hypertrophy was existent in only 35% of the LAD wrapping group which renders their LVMI 115 g/m2 close to the normal values. Moreover, previous investigators reported that the longitudinal LV strain is decreased in patients with hypertension [13, 36] whereas our study group showed no significant difference in longitudinal strain, between LAD wrapped and non-wrapped patients which preclude the influence of hypertensive left ventricular hypertrophy on cardiac mechanics that characterize LAD wrapping group.