Introducing a Novel Innovative Technique for the Recording and Interpretation of Dynamic Coronary Angiography

Abstract

In the study of coronary artery disease (CAD), the mechanism of plaque formation and development is still an important subject for investigation. A limitation of current coronary angiography (CAG) is that it can only show static images of the narrowing of arterial channels without identifying the mechanism of the disease or predicting its progression or regression. To address this limitation, the CAG technique has been modified. The new approach emphasizes identifying and analyzing blood flow patterns, employing methodologies akin to those used by hydraulic engineers for fluid or gas movement through domestic or industrial pipes and pumps. With the new technique, various flow patterns and arterial phenomena—such as laminar, turbulent, antegrade, retrograde, and recirculating flow and potentially water hammer shock and vortex formation—are identified, recorded, and classified. These phenomena are then correlated with the presence of lesions at different locations within the coronary vasculature. The formation and growth of these lesions are explained from the perspective of fluid mechanics. As the pathophysiology of CAD and other cardiovascular conditions becomes clearer, new medical, surgical, and interventional treatments could be developed to reverse abnormal coronary flow dynamics and restore laminar flow, leading to improved clinical outcomes.

1. Introduction

In the study of coronary artery disease (CAD), the precise mechanisms by which risk factors initiate and promote the progression of coronary lesions remain unclear. Furthermore, there is no consensus on why many lesions remain stable over extended periods, while others become unstable or acutely occluded [1,2,3]. To address this gap, our team has shifted focus from traditional biological studies and non-invasive imaging to employing fluid mechanics (FM) as the primary methodology for investigating healthy and diseased coronary arteries [4,5,6].

For FM engineers, laminar or helical flow is considered the ideal transportation modality in pipes because it maximizes efficiency and extends the life of equipment, while turbulent flow damages the inner surfaces of pipes and pump components. As a result, our research protocols have pivoted towards examining potential correlations between laminar flow, turbulent flow, and other arterial phenomena—including collisions and vortex formation—and their association with the presence, absence, progression, or regression of coronary plaques [7,8]. To elucidate the dynamic characteristics of coronary flows, our team has implemented a novel angiographic protocol, modifying the current conventional recording techniques [9,10,11].

In this article, first section provides a detailed description of the techniques used to accurately capture images of arterial flows and phenomena. The second section presents case studies that explore the potential correlations between coronary lesions and various flow patterns, elucidating the disease mechanisms from an FM perspective. Ultimately, the goal is to clarify the cardiovascular pathophysiology caused by flow disturbances, thereby enabling the development of innovative medical, surgical, and percutaneous interventions.

2. Dynamic Coronary Angiography

2.1. A New Technique in Dynamic Coronary Angiography

Currently, coronary angiography (CAG) involves filling the coronary artery with contrast to create a shadow of the lumen. This shadow is used to detect indentations, which are then identified as lesions or stenoses (Figure 1). However, this traditional method has a significant limitation: it only provides a static image of the narrowing in the arterial channel and does not offer insights into the disease mechanism or its potential progression or regression. To address this limitation, our team has developed a new technique by modifying the current angiographic recording sequence and reprogramming the reviewing protocol. This innovative approach allows for a more dynamic and comprehensive assessment of healthy and diseased coronary arteries.

The new dynamic angiographic technique aims to distinctly image and accurately identify various types of flows, such as laminar, helical, peripheral, antegrade, and retrograde flow, as well as arterial phenomena like vortex formation, water hammer shock, and turbulence. It is crucial to document the presence or absence of these flows and phenomena in the proximal segment, midsection, or distal region of a plaque. Additionally, the technique requires precise description and recording of the plaque’s border—whether it is clean and sharp or hazy—as these characteristics reflect the dynamic effects of normal or abnormal flows and the arterial phenomena on the plaque’s surface and endothelial layers.

By employing this new dynamic recording and reviewing technique, investigators can focus on identifying flows, analyzing their dynamics, and planning interventions. This approach adapts methodologies and practices commonly used by fluid mechanics or hydraulics engineers when transporting fluids or gases through residential or industrial pipes and pumps.

2.2. The Injection of Contrast and the Recording of Images

Initially, the contrast medium is injected until the index coronary artery is fully opacified. The manual injection stops when black-colored contrast is seen ejecting back from the coronary ostium into the aorta (Figure 2A). As blood enters the vessel, the shape, movements, directions, and interactions of the white-colored blood flow can be clearly observed and easily identified against the black contrast background (Figure 2B,C). The coronary angiogram is recorded from the start of the injection until all the contrast disappears from the distal arterial vasculature, marking the arterial phase (Figure 2D). The recording concludes after the contrast is flushed out of the coronary veins, marking the venous phase (Figure 3A–C).

During the recording, the camera is positioned at an angle that can record the index artery and vein at their full length, with all the images completely visible within the screen at 15 images per second (s) or 0.067 s or 67 milliseconds (ms) per image (67 ms is the interval between recorded images).

3. Angiographic Views

In the new dynamic angiographic recording, all the detailed movements of the blood (and contrast) need to be captured distinctly and identified accurately on the clean background of the lungs. The selected angles of the projector circumvent superimposing the arteriograms or venograms onto the bony structures of the spine or the myocardium filled with contrast at the end of the arterial phase and during the venous phase. The criteria of excellence when recording the angiogram are listed in

Table 1. Criteria of angiographic excellence.

1 The left main artery (LM) needs to be delineated in its entire length from the ostium to the bifurcation in order to capture all the fluid mechanics (FM) mechanisms of entry flow and angles of attack, which affect the formation of lesions at the upper versus lower border, in the middle or distal LM. 2 The transition from the LM to the left anterior descending artery (LAD) and left circumflex artery (LCX) has to be delineated so that all the mechanisms affecting bifurcated flows and lesions (laminar or turbulent, at the center or the side, at the entry and exit shoulders of the LAD and LCX) can be identified, timed, and recorded. 3 The proximal segments of the LAD and LCX must be seen clearly, mainly the outer curve of the proximal LCX and LAD. Usually, there is a boundary layer with recirculating flow, where plaques are commonly formed. 4 The bifurcations of the LAD with the diagonal and the LCX with the obtuse marginal artery need to be delineated well to detect the antegrade or retrograde flow or collision causing LAD and LCX lesions proximal to the bifurcation. 5 The mid-segment of the right coronary artery (RCA) is where most lesions are located. Here is the location of a collision between antegrade and retrograde flows, which possibly inflicts the initial injury and triggers the atherosclerotic process. 6 The distal segment of the RCA at the junction between the RCA and the posterior descending artery (PDA) and the posterior lateral branch (PLB), where the majority of distal and slow-growth lesions are located. 7 The junction between the proximal and mid-segments of the RCA (or any curved segment) where lesions could develop due to the repeated hinge motion of the angle connecting the two arterial segments.

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3.1. The Left Main Artery

The left main artery (LM) needs to be delineated at full length so the entry flow from the aortic root and the hydraulic phenomena in the mid-segment and the distal bifurcation can be captured. The best views for the ostial LM and the mid-segment are (1) the anteroposterior (AP) caudal view (Figure 4A,B) and (2) the left anterior oblique (LAO) caudal (spider) view. The flows in the LM can clarify the mechanism of entry flow and the angle of attack, which injures the intima at a specific location in the LM, starts a lesion, promotes its growth (at the upper or lower border), or ruptures its cover and precipitates acute coronary syndrome (Figure 5A–D).

3.2. The Left Anterior Descending Artery

In the left anterior descending artery (LAD), the flow to be seen is in the ostium, the outer curve or the upper border of the proximal segment, which is a preferred location for plaques, an area with low shear stress and at the distal end of the proximal segment [9]. The best views for the ostial and mid-segment LAD are:

• The left anterior oblique (LAO) caudal (spider) view for the ostium (Figure 6A,B)
• The left anterior oblique (LAO) cranial view for the proximal segment (Figure 7A,B)
• The anteroposterior (AP) cranial view for the proximal and mid-segments (Figure 8A,B)

3.3. The Left Circumflex Artery

In the left circumflex artery (LCX), the flow to examine is in the ostium, the outer curve opposite to the carina, the mid-segment, and the obtuse marginal (OM) branches. The best views for the ostial and mid-segment LCX are (1) the AP caudal view and the right anterior oblique (RAO) caudal view, which show the ostium and the proximal segment of the LCX and the branches of the OM well. The AP caudal view is used when the proximal segment of the LCX is not tortuous. The right anterior oblique (RAO) caudal view is better when the proximal segment is curved or tortuous (Figure 9A,B).

3.4. The Right Coronary Artery

In the right coronary artery (RCA), the flows to look for are listed in

Table 2. List of locations to focus on in the right coronary artery.

1 The ostium, its orientation, and the angle formed by the proximal segment of the artery with the aortic wall (to investigate the mechanism of ostial lesions) 2 The angle connecting the proximal to the mid-segment (to check the hinge motion) 3 The mid-segment (to check the collision between antegrade and retrograde flows: most likely due to the water hammer shock phenomenon) 4 The junction between the mid- and distal segments (to check the hinge motion) 5 The bifurcation with the posterior descending artery and the posterior lateral branch (to check the recirculating flow caused by blood from convergent branches in a retrograde direction)

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The best view for the flow in the ostial, proximal, and mid-RCA is the LAO caudal view (spider view) (Figure 10A). The LAO cranial view is the best view for flow in the distal RCA and bifurcation with the posterior descending artery and posterior lateral branch (Figure 10B).

3.5. Analysis Using Artificial Intelligence Programs

Extensive utilization of computational fluid dynamics studies, artificial intelligence, and deep learning packages and programs was initiated in our research protocols and aimed to optimize the research methodology on flows and arterial phenomena, systemize the protocol for angiographic interpretation, and give the preliminary online results without the need for offline manual image review [12,13,14,15,16,17].

4. Clinical and Imaging Correlations

In patients with cardiovascular (CV) disease, there are many clinical situations in which the pathophysiology is still not well elucidated. They are listed in

Table 3. List of cardiovascular conditions with unexplained pathophysiology.

1 Chest pain and sudden death in patients with aortic stenosis (AS) and patent coronary arteries. 2 Chest pain and sudden death in patients with anomalous coronary artery from the opposite aortic sinus of Valsalva (ACAOS) and patent coronary arteries. 3 Chest pain and sudden death in patients with dilated cardiomyopathy and patent coronary arteries. 4 Progression or regression of coronary lesion of moderate stenosis. 5 What is the mechanism of the formation and growth of lesions in the mid-segment of the right coronary artery? Could it be the water hammer shock phenomenon? 6 What is the mechanism of the formation and growth of lesions at the outer border of the ostium of the left circumflex? Could it be vortex formation from recirculating flow? 7 What is the mechanism of the benefit of stenting? Could it be due to restoring laminar flow? 8 In patients with new dilated cardiomyopathy and a low ejection fraction (EF), could a normal coronary dynamic flow predict the return to a normal EF with treatment?

. Can the new images obtained through dynamic coronary angiography, depicting both normal and abnormal arterial flows or phenomena, contribute to understanding the pathophysiological mechanisms of disease from an FM perspective? Additionally, could rectifying these disturbances in flow aid in proposing viable therapeutic solutions?

4.1. Correlation Case Study 1—Turbulence from Recirculating Flow and an Ostial Lesion in the Side Branch

In the coronary angiograms of middle-aged patients, many have only subtle, minimal lesions in the ostium of the left circumflex artery (LCX) (Figure 11A). This is a slow-growth lesion, especially in patients with well-controlled hypertension and hyperlipidemia. Why are the lesions discovered first at this particular ostial LCX location when there are no visible lesions in other segments of the coronary vasculature? What is the FM explanation for this angiographic observation? From an FM perspective, when the fluid arrives at the bifurcation of a pipe, the fluid layers at the center of the divergent side branch (SB) exhibit a higher velocity compared to the peripheral layers adjacent to the outer wall (Figure 11B) [18].

When the velocity and pressure differences between the central and peripheral layers reach a critical threshold, the innermost layers detach from the boundary layer of the inner wall (Figure 12). This detachment causes the layers to curl upon themselves, resulting in the formation of recirculating flows and a stagnant area near the wall. Within this stagnant region, the flow velocity decreases, and pressure increases according to the Bernoulli equation. If the recirculating flows are sufficiently strong, they can evolve into vortices—swirling masses of fluid with rapid rotational motion. Ultimately, these vortices gradually decay into disorganized flow or turbulence (Figure 9A–D) [18].

The early development of lesions in the ostial LCX is attributed to this segment being confined within a narrow atrioventricular (AV) groove. Initially, as an atherosclerotic plaque forms, it gradually intrudes into the lumen, leading to flow obstruction. In response, the artery compensates by expanding, maintaining the lumen’s surface area despite the increasing plaque volume (Figure 13). However, because the proximal LCX is constrained within the AV groove, it lacks the capacity to expand. Consequently, lesions in the proximal segment of the LCX become noticeable earlier than those of a similar size in other coronary locations.

In patients with lesions in the distal RCA, proximal to the bifurcation with a posterior descending artery, the mechanism of recirculating flow could be similarly applied. However, lesions form due to recirculating flow in the separation zone where the blood converges from the two branches in the retrograde direction (Figure 14A,B and Figure 15A–F).

4.2. Correlation Case Study 2—Coronary Lesions and Laminar versus Turbulent Flow

For patients with a moderate 50% stenotic lesion, some may become unstable unpredictably, while many others remain asymptomatic for an extended period [3]. No clinical nor testing criteria can reliably predict the progression nor regression of these lesions. How can this problem be addressed from an FM perspective?

Using the new dynamic coronary angiographic technique, it has been observed that laminar flow is the most common flow pattern in coronary arteries (Figure 2C). According to FM principles, laminar flow protects the lining of pipes, the components of pumps, and the banks of waterways, whereas turbulent flow damages them [20,21]. Applying these FM principles to cardiovascular (CV) disease research, one can question whether turbulent flow at a coronary lesion further damages the plaque, ruptures its cap, and precipitates acute coronary syndrome (ACS). Conversely, could laminar flow at the lesion maintain the stability of the plaque cover and the integrity of the endothelial cell layer? If so, does laminar flow also inhibit plaque growth and sustain a patient’s stable angina (SA) condition? These questions were examined in the following study [22,23].

A group of patients admitted with unstable angina underwent a new dynamic angiogram. They were selected based on the presence of a single moderate lesion in a straight coronary segment, distant from any bifurcation. The angiographic risk factors evaluated were laminar flow versus disorganized or turbulent flow across the lesion. All patients received the optimal medical management to maintain their blood pressure below 120 mmHg and their low-density lipoprotein (LDL) levels below 75 mg/dL (Figure 16A–F). The clinical endpoints were persistent stable angina versus acute coronary syndrome (ACS) requiring percutaneous intervention.

The results showed that patients with baseline laminar flow remained stable, neither develo** ACS nor requiring percutaneous or surgical intervention at the two-year follow-up (Figure 16A–F). In contrast, 83% of patients with baseline turbulent flow across a moderate-sized lesion developed ACS within six months. This pilot study suggests the protective effect of laminar flow and an increased risk of plaque rupture due to turbulent flow [23]. Large randomized studies are needed to confirm these observations.

4.3. Correlation Case Study 3—Retrograde Flow Causing Chest Pain and Sudden Death

Many patients with aortic stenosis (AS) and patent coronary arteries experience chest pain (CP) and sudden cardiac death (SCD). What is the pathophysiological mechanism underlying these two classic symptoms of AS? Similarly, patients with dilated cardiomyopathy or anomalous coronary artery from the opposite aortic sinus of Valsalva (ACAOS) also present with CP and SCD. How can the disease mechanisms in these conditions be explained from an FM perspective?

Under normal conditions, using the new dynamic angiographic technique, coronary blood flow is observed moving forward, faster during diastole and more slowly during systole, due to the higher-pressure gradient between the aortic root and the left ventricle during diastole. Conversely, retrograde flow is rare and brief. However, in extreme cases, such as patients with ACAOS combined with an inter-arterial course between the aorta and the pulmonary trunk, the proximal segment may prominently show retrograde flow of the black contrast, spilling into the aortic sinus. With the dynamic coronary angiography technique, the retrograde flow of the contrast in black and the antegrade flow of the blood in white can be simultaneously observed at the proximal and distal ends of the flow (Video S1).

This slow antegrade and intermittent retrograde flow can also be observed in patients with severe uncontrolled hypertension (systolic blood pressure > 200 mmHg) without coronary lesions. In contrast, patients with dilated cardiomyopathy and patent coronary arteries exhibit a significant delay in antegrade flow without the presence of retrograde flow. Consequently, both slow antegrade and reverse coronary flows hinder the timely delivery of highly oxygenated blood to the myocardium, leading to significant functional ischemia despite the absence of obstructive coronary lesions [24,25,26].

4.4. Correlation Case Study 4—Collision at the Middle of the Right Coronary Artery

In patients with CAD, many have lesions in the mid-RCA. What alterations in flow dynamics could contribute to the development of lesions in the mid-RCA segment? In a patient with unstable angina and a severe lesion in the RCA, static images or videos may show antegrade flow, stagnation of the contrast at the transition between systole and diastole, or a collision between antegrade and retrograde flows. How can these arterial flow dynamics be explained from an FM perspective? Could this phenomenon be analogous to a water hammer shock event? (Figure 17A–F, Video S2).

4.5. Fluid Mechanics: Water Hammer Shock in Pipes

Water hammer shock, or hydraulic shock, is a transient phenomenon in fluid flow systems, particularly in pipelines. It occurs when there is an abrupt change in flow velocity or direction, typically triggered by sudden valve closures or rapid pump start/stop actions [27]. This sudden change in flow velocity generates a pressure surge within the system, accompanied by the formation of pressure waves that propagate through the fluid at the speed of sound, exceeding the actual flow velocity. When these pressure waves encounter alterations in the pipe system, such as closed valves or bends, they reflect back into the pipe, leading to a subsequent pressure build-up. As these pressure waves reflect back and forth within the pipe system, they can amplify each other, resulting in a rapid increase in pressure—a phenomenon known as the water hammer effect. The sudden surge in pressure can exert significant stress on the pipe walls, potentially causing vibrations, noise, and damage to pipes, fittings, and other system components if not adequately controlled (Figure 18).

4.6. Water Hammer Shock in Coronary Arteries

In a similar context, considering the aorta as a tank and the coronary artery as an outflow pipe, the forward movement of coronary blood resembles fluid drainage. During the initial phase of systole, the left ventricle (LV), acting as a proximal valve, contracts, causing the coronary blood to temporarily halt at the distal myocardium. Over time, this results in the accumulation of stationary blood. Simultaneously, the contraction of the LV compresses the myocardial capillary network, forcing the stationary blood to move backward and collide with the anterograde flow, particularly at the transition from diastole to systole. This collision induces turbulence, leading to injury to the intima and promoting the atherosclerotic process (Video S2). Based on the sequence of images illustrating this collision, it suggests many similarities to a water hammer shock event in a pipe (Figure 17A–F).

4.7. Angiographic and Clinical Interventions

The collision between antegrade and retrograde flows, or water hammer events, is frequently observed in the mid-RCA, the distal end of the proximal segment of the LAD and LCX, and the iliac artery. This phenomenon occurs during the transition between diastole and systole, when retrograde systolic flow clashes with antegrade diastolic flow. This detail is crucial, as it suggests that the preferred location for coronary lesions is determined more by temporal factors (timing) than anatomical factors (location). Lesions develop wherever coronary flow reaches by the end of diastole, transitioning to left ventricular contraction in systole.

As turbulent flow is the most plausible cause of atherosclerosis, the benefit of stenting may lie in eliminating turbulent flow and restoring laminar flow (Video S3). Well-controlled systolic blood pressure and a decreased rate of pressure rise (dp/dt) achieved through beta-blockers can attenuate the effects of retrograde flow and reduce turbulence at collision sites. This mechanism likely underlies the benefits of controlled hypertension and beta blockade in preventing coronary artery disease (CAD) and myocardial infarction [28].

5. Conclusions

The investigation of coronary artery disease (CAD) predominantly centers on understanding the mechanisms underlying plaque formation, progression, and regression. The introduction of novel techniques for recording and interpreting coronary angiography has facilitated the identification of diverse flow patterns and arterial phenomena within coronary arteries. These newly elucidated flow dynamics suggest that the formation and growth of coronary lesions are primarily attributed to disorganized flow or turbulence. Turbulent flow causes injury to the intima, initiating the development of small lesions and fostering their progression, particularly in the presence of abundant low-density lipoprotein (LDL) cholesterol molecules. Uncontrolled hypertension exacerbates the repetitive impact of turbulent flow, increasing the likelihood of plaque rupture. This pathological mechanism is implicated in precipitating acute coronary syndrome, ST-elevation myocardial infarction, critical limb ischemia, transient ischemic attack, stroke, and other related conditions. The adoption of this innovative approach to recording and reviewing coronary dynamic flows, along with their clinical implications, has ushered in a new era of valuable insights and innovative applications for the diagnosis and medical, surgical, and interventional management of patients with CAD.