Details of Left Ventricular Remodeling and the Mechanism of Paradoxical Ventricular Septal Motion After Coronary Artery Bypass Graft Surgery

ABSTRACT: Objective. The purpose of this study was to obtain new details of three-dimensional left ventricular wall motion related to ventricular remodeling in patients undergoing coronary artery bypass graft (CABG) surgery. Methods. Cardiac-gated, phase-contrast measurements using navigator-gated, high temporal resolution, tissue phase mapping were obtained on 19 patients (66 ± 7 years old) before and after CABG. Left ventricular motion patterns and myocardial velocities were recorded for radial, circumferential and longitudinal motion. Radial, circumferential and longitudinal velocity curves were obtained separately for 16 ventricular segments. Ventricular torsion rate and longitudinal strain rate were also derived pre- and post-surgery. Results. After CABG, there was a significant improvement in apical contraction, with an apparent paradoxical decrease in the radial inward motion of the septal segments at the left ventricular base. Despite improved ventricular contractility during systole, peak longitudinal and rotational velocities decreased or showed no significant changes. An altered pattern of rotational motion with decreased initial counter-clockwise rotation at the beginning of systole and subsequent lower amplitude of reversed motions in diastole was also noted in most left ventricular segments. Lower peak clockwise rotational velocities were recorded in the basal anteroseptal segment with relatively higher values in the rest of the basal segments. Conclusion. Our results suggest that post-operative changes after CABG are limiting ventricular rotational and longitudinal motions, despite an increase in ventricular contractility due to revascularization. At the ventricular base, the restrained rotational motion of basal anteroseptal segment, located proximally to the right ventricular insertion, and higher rotational velocities of the rest of the segments are pushing the septum toward the right ventricle during ventricular twisting. At the ventricular apex, the restrain in rotational motion caused by post-operative adhesions is affecting all apical segments due to a much smaller left ventricular diameter at this level. The rotating apex and the apical septum are similarly displaced toward the right ventricle during ventricular twisting.  

J INVASIVE CARDIOL 2011;23:276–282

Key words: paradoxical septal motion, CABG, ventricular wall motion, cardiac magnetic resonance imaging, tissue phase mapping

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Currently used technologies for the prediction of myocardial viability, such as dobutamine stress echocardiography,^1–3 positron emission tomography^4,5 and nuclear imaging,^3,6 lack sufficient accuracy in the setting of severely depressed ventricular function, when such a prediction is most critical in planning surgical therapy to maximize benefit and minimize risk.^7,8 Consequently, the development of non-invasive techniques for quantitative assessment of regional ventricular function before and after surgical intervention requires further development.⁷ In addition, it has been shown that regional wall-motion abnormalities in patients undergoing coronary artery bypass graft (CABG) surgery have prognostic importance,⁹ and that deterioration of regional wall motion immediately after CABG is associated with long-term major adverse cardiac events.¹⁰

In this study, navigator-gated, high temporal resolution tissue phase mapping (TPM) has been used to analyze global and regional left ventricular (LV) wall motion in a group of patients undergoing CABG surgery for myocardial revascularization.

Methods

Study participants. Nineteen patients (18 male) aged 66 ± 7 years underwent cardiac magnetic resonance imaging before CABG and 6 months later. All patients had three-vessel coronary disease, defined as > 50% stenosis. In addition, 14 of these patients had stenotic lesions involving the left main segment (Table 1, Figure 1). Twelve patients had previous myocardial infarcts (5 of them within the last 6 months). Most patients had significant risk factors for coronary artery disease (Table 2), including hypercholesterolemia (15 patients), hypertension (12 patients), diabetes mellitus (8 patients), peripheral vascular disease (6 patients), and smoking (9 patients, with an average smoking history of 38 ± 8 pack-years). Most patients were taking lipid-lowering medication (18 patients), aspirin (16 patients), ACE inhibitors (17 patients), beta blockers (14 patients) and diuretics (6 patients). Changes in LV volumes and function before and 6 months post-CABG are summarized in Table 3. The period was chosen to avoid the confounding variables related to early post-operative period and to ensure a complete functional recovery after traumatic surgery.

The study was performed according to the principles of the Declaration of Helsinki and was approved by a local Oxfordshire Clinical Research Ethics Committee. Each subject provided written informed consent.

Cardiac MR scan. Cardiac MR examinations were performed with a 1.5 T MR clinical scanner. A set of cine images using a steady-state free precession (SSFP) sequence was acquired for the evaluation of the global parameters (Table 3). Cine images for navigator-gated high temporal resolution TPM were acquired using a black blood prepared segmented k-space gradient echo sequence^11,12 (TR = 6.9 msec; flip angle = 15º; bandwidth = 650 Hz/pixel; field of vision = 400 x 300 mm; matrix = 256 x 96) with a temporal resolution of 13.8 ms. Three equidistant short-axis positions along the LV were obtained. The basal slice was positioned parallel to the base of the heart and distal to the LV outflow tract. Basal, mid-ventricular and apical slices were positioned 15–20 mm apart, depending on the heart size. Depending on the navigator efficiency of the respiratory gating, each short-axis acquisition took approximately 3–5 minutes.

TPM analysis was performed with customized software (Matlab, version 6.5; Mathworks, Natick, Massachusetts). The endocardial and epicardial borders were contoured manually for base, mid-ventricle and apex in each phase of the cardiac cycle, excluding papillary muscles. The end systole for each slice was determined as the time point corresponding to the smallest LV cavity. The cardiac phases were subsequently calculated and normalized for the entire group based on their average duration during a cardiac cycle. Global ventricular velocity time courses for radial, circumferential and longitudinal motion were calculated for each group by averaging over the entire segmentation mask, as well as the corresponding peak velocities and time-to-peak. In addition, graphical representations of radial and circumferential velocities during a cardiac cycle for individual LV segments were obtained. Visual assessment of individual segmental radial, circumferential and longitudinal velocity graphs revealed no significant difference to account for a particular motion pattern in any subject (e.g., large scars, regional paradoxical motion, etc.). Global ventricular torsion and strain rates were also determined.

Statistical analysis. Following TPM analysis, the MatLab files were converted and generated into Excel files, allowing further statistical analyses. Subsequently, all data were analyzed using SPSS, version 16.0 (SPSS, Inc., Chicago, Illinois) and Microsoft Office Excel 2003. The variables were tested for normal distribution and, after the assumption was met, a paired t-test was used to compare the values obtained before and after CABG. A p-value of less than 0.05 was considered significant. The reproducibility of the measurements using navigator-gated TPM was evaluated in a previous study, with repeated MR scans performed on 14 healthy volunteers three weeks apart. The method showed high reproducibility and a coefficient of variation for repeated values between 9.3 and 11.4% for different parameters (unpublished data).

Results

Radial motion. A graphical representation of radial velocities at the LV base, mid-ventricle and apex during a cardiac cycle is shown in Figures 2A–2C. The graphs represent average values for all volunteers before and after CABG. Positive values reflect LV segmental motion toward the center of the ventricle, while negative values reflect an outward motion. The peak systolic and diastolic radial velocities at the LV base, mid-ventricle and apex and their corresponding peak times are presented in Table 4. Radial velocity traces for individual LV segments are provided in Figure 3. 

After CABG, there was a significant improvement in apical contraction (Figure 2C, arrow a), from 2.4 ± 0.2 cm/s to 3.1 ± 0.2 cm/s (p = 0.03), with peak systolic radial velocities at the ventricular apex reaching those at the LV base (Table 4). Diastolic radial velocities, however, showed no significant changes after revascularization (Table 4 and Figure 2, arrow b), the difference being not statistically significant (p-values between 0.20 and 0.57). Segmental velocity graphs (Figure 3) confirmed a significant improvement in contractility of the apical segments after revascularization, particularly in antero-posterior direction (i.e., segments 13 and 15). There was an apparent paradoxical decrease in the radial inward motion of the basal septal segments (segments 2 and 3) after CABG (Figure 3). No difference in the time to peak systolic and diastolic radial velocities was noted after revascularization compared to pre-operative values (Table 4).

Rotational motion. Peak clockwise and counter-clockwise circumferential velocities are provided in Table 3. Positive values reflect clockwise rotation and negative values reflect counter-clockwise rotation as viewed from the apex. The graphical representation of circumferential velocities at the LV base, mid-ventricle and apex is shown in Figures 2D–2F, while rotational motion of individual segments is shown in Figure 4.

An altered pattern of rotational motion with a lower wave of counter-clockwise rotation of the entire LV at the beginning of systole (Figures 2D–2F, arrow c) as well as a subsequent lower wave of ventricular untwisting in diastole (Figures 2D–2F, arrow f) was noted after CABG. This changed pattern of rotational motion could be better appreciated on graphical display (Figures 2D–2F) and has not always affected the peak rotational velocities (Table 4). For example, the counter-clockwise rotation of the LV base at the beginning of systole was significantly limited or apparently absent in most CABG patients (Figure 2D, wave c is above zero after CABG). The peak counter-clockwise velocity at the LV base indicated in Table 4, however, was represented by a recoil wave of untwisting during diastole (Figure 2D, the highest negative wave e) and could not reflect the noted changes in counter-clockwise rotation at the beginning of systole (Figure 2D, wave c). The time required to reach peak clockwise velocities at the LV base was also shorter after CABG (42.9% of end-systole compared with 51.5% of end-systole before CABG; p < 0.01; Table 4), confirming a changed pattern of rotational motion.

The segmental velocity graphs at the LV base showed lower peak clockwise rotational velocities in anteroseptal segment (segment 2) after CABG, with relatively higher values in the rest of the basal segments (Figure 4, segments 1 and 3–6). An altered pattern of rotational motion with decreased initial counter-clockwise rotation at the beginning of systole and subsequent lower amplitude of reversed motions in diastole was also noted in most LV segments.

Longitudinal motion. Peak longitudinal velocities with corresponding time to peak values for main LV slices before and after CABG are presented in Table 4, while the graphical display is provided in Figures 2G–2I. Positive values demonstrate downward motion along the longitudinal LV axis (i.e., toward the apex) and negative values show upward motion (i.e., toward the base).

Similar to rotational velocities, the peak longitudinal velocities decreased or showed no significant changes in most patients after cardiac surgery, likely underscoring limitations in ventricular motions along its longitudinal axis, despite increased radial contractility (Table 4).

Evaluation of global ventricular torsion rate and longitudinal strain rate after CABG. The obtained peak values for ventricular torsion rate and longitudinal strain rate, as well as their corresponding peak times, are provided in Table 5, while the graphical display is shown in Figure 5. No significant changes have been found after CABG.

Segmental motion. Visual assessment of segmental radial, circumferential and longitudinal velocity graphs in individual patients revealed no gross wall motion abnormalities in any particular LV segments to account for outliers. Since all patients included in the study had triple-vessel coronary artery disease, no significant difference between affected myocardial regions was expected. Given the number of resulting parameters (16 segments x [3 velocities + 3 time to peak values] = 96 parameters), no myocardial velocities for individual segments were calculated in this case, the evaluation being more suitable for patients with regional rather than global ischemic heart disease.

Discussion

The higher peak systolic radial velocities at the LV apex show an improved myocardial contractility following revascularization. The mechanism of the lower initial counter-clockwise velocities after CABG, however, might include two components. Kroeker et al¹³ have shown that ischemia induced by a short period of coronary artery occlusion in animal models resulted in increased counter-clockwise rotation. As a probable explanation, the authors provide the loss of counteraction of contraction of subendocardial, clockwise-oriented cardiomyocytes because of subendocardial ischemia.^13,14 First, myocardial revascularization might improve the contraction of ischemic subendocardial cardiomyocytes, thus increasing their counteraction component. Second, and even more importantly, the post-operative adhesions developing after open cardiac surgery^15,16 are expected to significantly limit rotational motions of the entire ventricle. The mechanism would also explain the obvious limitations of rotational motions for most segments, despite increased radial contractility after CABG.

The new details of rotational motion of individual segments obtained using navigator-gated TPM might also prove helpful in clarifying the origin of the paradoxical septal motion after cardiac surgery. The phenomenon has been described since the early days of echocardiography;^17,18 however, its mechanism remains unclear.¹⁹

Segmental circumferential velocities showed decreased clockwise velocities in basal anteroseptal segment (segment 2) after CABG (Figure 3), despite increased peak clockwise values in all other basal LV segments (segments 1 and 3–6). A diagram of the likely mechanism is provided in Figure 5. It is well recognized that numerous post-operative adhesions developing after cardiac surgery attach the anterior surface of the heart, i.e., the right ventricle (RV), to the chest wall, making the dissection process particularly challenging during reinterventions.¹⁵ This was confirmed by cardiac MR studies, showing that separation of the RV wall from the chest wall during systole decreased after CABG and that despite preserved RV function, there was restricted motion of the RV free wall suggestive of post-operative adhesions.¹⁸ However, a relatively fixed RV is expected to directly affect the rotational motion of the LV during systole. Since the insertion line of the RV is just anterior to the anterior septum, it affects directly the clockwise rotation of the anteroseptal segment (segment 2) during LV twisting, the septum being pushed toward the RV (Figure 5). Additionally, during cardiac surgery, the aorta is separated from pulmonary artery and surrounding tissues, being prepared for cardiopulmonary bypass and clamping. The employed surgical dissection and aortic manipulation are expected to result in significant post-operative adhesions, affecting aortic root and adjacent antero-superior septum at the LV base, further limiting the rotational motion of these structures. Since the rotational motion of other basal LV segments is higher, the ventricular septum is being displaced toward the RV (Figure 5). The ventricular septum at the LV apex is similarly displaced toward the RV during systole (Figure 5), although the restrain in rotational motion caused by the RV is expected to affect all apical segments due to a much smaller LV diameter at this level (Figure 3, segments 13–16).

The described mechanism is consistent with previous reports showing normal perfusion of the paradoxically moving septum,^20,21 and is supported by cardiac MR findings that the entire LV translocates anteriorly in systole after CABG, with the heart lifting against gravity during systole even when patients lie supine in the MRI scanner.¹⁸ The mechanism would also explain the appearance of paradoxical ventricular septal motion after other types of cardiac surgery or fibrotic adherent pericarditis due to other causes.²²

Although considered to have little clinical significance, marked paradoxical septal motion needs to be differentiated from other conditions, such as septal dyskinesia due to myocardial infarction or ischemia.^18,23,24 The mechanism can also explain the lower peak systolic radial velocities in segment 3 after CABG (Figure 2), the segment being pushed toward the RV during systole (Figure 5).

The lower longitudinal velocities recorded after CABG can also be attributed to post-operative fibrosis and adherences that attach the ventricular surface to surrounding tissues, affecting mediastinal anatomy and limiting LV rotational and longitudinal motions. In addition, other factors such as pulmonary hypertension, primary or developed RV dysfunction may contribute to the paradoxical septal motion; however, we do not have enough data to support such a mechanism in this study. Moreover, the evaluation of RV function in these patients was the subject of a separate study, which concluded that the function of the RV recovered completely by 6 months, with normalization of all volumetric parameters after revascularization.

Our findings suggest that post-operative adhesions play a major role in ventricular remodeling after cardiac surgery, being also the cause of paradoxical ventricular septal motion. The effects of this remodeling on ventricular contraction and cardiac hemodynamics may require further investigations, especially as preventive measures have been proposed.

Study limitations and perspectives. Most patients included in this study are male. Peri-procedural injury may have also influenced regional wall motion post-surgery. The cardiac phases were calculated and normalized for the entire group based on their average duration during systole and diastole and not on the timing of cardiac valves closure and opening, which was not recorded. The phases are provided for general orientation and even when slightly displaced would not affect data interpretation. 

Since all patients included in the study had triple-vessel ischemic heart disease, no significant difference between affected myocardial areas was expected and no segmental analysis was performed. Evaluating segmental velocities and regional myocardial motion in patients with a single-vessel coronary disease and correlating areas of regional wall motion abnormalities with the affected coronary artery represents an excellent foreground for further studies. Given the findings suggesting that post-operative adhesions play a major role in ventricular remodeling after cardiac surgery, evaluating ventricular wall motion in patients treated with percutaneous coronary interventions versus open cardiac surgery would be of particular interest.  

Acknowledgments. This work was supported by a direct project grant from the British Heart Foundation (grant number PG/05/037), by the Oxfordshire Health Services Research Committee (OHSRC reference G) and by the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the Department of Health's NIHR Biomedical Research Centres funding scheme.

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From ¹the Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom, ²the University of Oxford Centre for Clinical Magnetic Resonance Research, Oxford, United Kingdom, ³the Department of Cardiovascular Medicine, Flinders University, Bedford Park SA 5042, Australia, ⁴Saint Francis Hospital and Medical Center, Hartford, Connecticut, ⁵the Department of Diagnostic Radiology, Medical Physics, University Hospital, Freiburg, Germany, and ⁶the Department of Cardiothoracic Surgery, John Radcliffe Hospital, Oxford, United Kingdom.
The authors have no conflicts of interest to declare.
Manuscript submitted February 8, 2011, provisional acceptance given March 15, 2011, final version accepted May 2, 2011.
Address for correspondence: Dr. Ion Codreanu, Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford, United Kingdom. Email: codrion@yahoo.com