Effects of Mechanical Dyssynchrony on Coronary Flow: Insights From a Computational Model of Coupled Coronary Perfusion With Systemic Circulation.
ABSTRACT: Mechanical dyssynchrony affects left ventricular (LV) mechanics and coronary perfusion. Due to the confounding effects of their bi-directional interactions, the mechanisms behind these changes are difficult to isolate from experimental and clinical studies alone. Here, we develop and calibrate a closed-loop computational model that couples the systemic circulation, LV mechanics, and coronary perfusion. The model is applied to simulate the impact of mechanical dyssynchrony on coronary flow in the left anterior descending artery (LAD) and left circumflex artery (LCX) territories caused by regional alterations in perfusion pressure and intramyocardial pressure (IMP). We also investigate the effects of regional coronary flow alterations on regional LV contractility in mechanical dyssynchrony based on prescribed contractility-flow relationships without considering autoregulation. The model predicts that LCX and LAD flows are reduced by 7.2%, and increased by 17.1%, respectively, in mechanical dyssynchrony with a systolic dyssynchrony index of 10% when the LAD's IMP is synchronous with the arterial pressure. The LAD flow is reduced by 11.6% only when its IMP is delayed with respect to the arterial pressure by 0.07 s. When contractility is sensitive to coronary flow, mechanical dyssynchrony can affect global LV mechanics, IMPs and contractility that in turn, further affect the coronary flow in a feedback loop that results in a substantial reduction of dP LV /dt, indicative of ischemia. Taken together, these findings imply that regional IMPs play a significant role in affecting regional coronary flows in mechanical dyssynchrony and the changes in regional coronary flow may produce ischemia when contractility is sensitive to the changes in coronary flow.
Project description:Objective:Basic science studies demonstrated a general intramyocardial angiogenetic response potentially responsible for the creation of a microvascular neocapillaries network assisting myocardial function. We hypothesized that the benefit provided by the reperfusion of left anterior descending (LAD) territories and the biological angiogenetic drive triggered by the revascularization could translate in a global improvement in ventricular contractility, not restricted to the grafted area. Methods:High-risk patients with multivessel coronary artery disease and preoperative wall motion abnormalities were retrospectively analyzed to compare outcomes and regional ventricular function of those who received optimal medical therapy (OMT) versus those who underwent off-pump coronary artery bypass grafting (OPCABG) and received an incomplete myocardial revascularization using left internal mammary artery (LIMA) on LAD (OPCABG group). From January 2007 to December 2014, 206 patients (OMT, n = 136, OPCABG, n = 70) were propensity-score matched to have 70 matched pairs. Variables included in propensity score analyses were ejection fraction (EF), left ventricular end diastolic volume (LVEDVi), EuroSCORE II. Primary endpoint was the variation in the global wall motion score index (?WMSI) as evaluated by transthoracic echocardiography. Follow up was completed at 3 years from surgery or hospital discharge. Results:Regional analysis of ventricular function revealed a regional WMSI improvement in the OPCABG group not only for LAD territories but also for non-LAD regions, associated with a reduction in the negative left ventricular ischemic remodeling, compared to patients discharged in optimal medical therapy. Global ?WMSI was negative in OPCABG group (-3.4 ± 2.8%) and positive in the OMT group (5.9 ± 3.1%), indicating a better wall motion score for OPCAB patients. Surprisingly, regional WMSI improved also in non-grafted territories in the off-pump CABG group with a delta value of -3.7 ± 5.3% for left circumflex artery (LCX) area and -3.5 ± 5.4% for right coronary artery (RCA) area. Conclusions:In patients with multivessel coronary artery disease, LIMA-to-LAD grafting is associated with an improvement in the WMSI involving also the surrounding non-LAD ungrafted segments and with the attenuation of negative global and regional ischemic ventricular remodeling.
Project description:PURPOSE:To evaluate the diagnostic performance of left coronary bifurcation angles and plaque characteristics for prediction of coronary stenosis by dual-source CT. METHODS:106 patients suspected of coronary artery disease undergoing both coronary computed tomography angiography (CCTA) and invasive coronary angiography (CAG) within three months were included. Left coronary bifurcation angles including the angles between the left anterior descending artery and left circumflex artery (LAD-LCx), left main coronary artery and left anterior descending artery (LM-LAD), left main coronary artery and left circumflex artery (LM-LCx) were measured on CT images. CCTA plaque parameters were calculated by plaque analysis software. Coronary stenosis ? 50% by CAG was defined as significant. RESULTS:106 patients with 318 left coronary bifurcation angles and 126 vessels were analyzed. The bifurcation angle of LAD-LCx was significantly larger in left coronary stenosis ? 50% than stenosis < 50%, and significantly wider in the non-calcified plaque group than calcified. Multivariable analyses showed the bifurcation angle of LAD-LCx was an independent predictor for significant left coronary stenosis (OR = 1.423, P = 0.002). In ROC curve analysis, LAD-LCx predicted significant left coronary stenosis with a sensitivity of 66.7%, specificity of 78.4%, positive predictive value of 85.2% and negative predictive value of 55.8%. The lipid plaque volume improved the diagnostic performance of CCTA diameter stenosis (AUC: 0.854 vs. 0.900, P = 0.045) in significant coronary stenosis. CONCLUSIONS:The bifurcation angle of LAD-LCx could predict significant left coronary stenosis. Wider LAD-LCx is related to non-calcified lesions. Lipid plaque volume could improve the diagnostic performance of CCTA for coronary stenosis prediction.
Project description:We present the case of 56-year-old woman who required complex coronary artery bypass grafting for high-risk anomalous left main coronary artery (LMCA) originating from right coronary cusp including conventional reimplantation of the LMCA plus left internal mammary artery (LIMA) graft to the left anterior descending (LAD) and saphenous vein graft (SVG) to the left circumflex (LCx). On subsequent cardiac computed tomography screening and cardiac catheterization, the LIMA graft was occluded after just a few centimeters, but the SVG graft was patent with good run-off into the native LCx and also filled the LAD retrogradely. The reimplanted left main stem demonstrated at least moderate ostial stenosis although pressure wire assessment of this was not significant (fractional flow reserve 0.89), probably due to good retrograde filling of the LAD from the SVG to LCx, therefore, we did not proceed with ostial LMCA stenting. She remains on yearly review with a low threshold for further revascularization should the SVG to LCx develop progressive stenosis. This case illustrates how patients with anomalous LMCA may sometimes benefit from grafting in addition to conventional reimplantation.
Project description:BACKGROUND:A wider angle between the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX) has been suggested to induce plaque formation in the arterial system via changes in shear stress. However, the relationship between the left main coronary artery (LM)-LAD angle and LAD stenosis has not been investigated. Therefore, we aimed to evaluate the associations between the LM-LAD and LAD-LCX angles and LAD stenosis. METHODS:Coronary computed tomography angiographies (CTAs) of 201 patients with suspected coronary artery disease were analyzed. Angle measurements were performed twice by experts using CTA images, and the values were averaged. The patients were divided into two groups, based on the presence of significant LAD stenosis (luminal diameter narrowing ?50%) on CTA. RESULTS:The mean LM-LAD and LAD-LCX angles were 37.46° and 63.04°, respectively. The LM-LAD and LAD-LCX angles of the group with significant LAD stenosis were significantly wider than that of the group with nonsignificant LAD stenosis (P<0.001; P = 0.020, respectively). In a multivariate analysis, an LAD-LCX angle greater than 60° showed a trend toward predicting significant LAD stenosis (HR, 3.14; 95% CI: 0.96-1026; P = 0.058). In contrast, an LM-LAD angle greater than 40° was a significant predictor of significant LAD stenosis (HR, 12.2; 95% CI: 2.60-56.52; P = 0.001). CONCLUSIONS:The results of the present study may suggest that a wider LM-LAD angle could be used to identify patients at higher risk for coronary artery disease (CAD). Thus, close follow-up and preventive management of other risk factors may be needed in such cases.
Project description:The role of atherosclerosis in the progression of global left ventricular dysfunction and cardiovascular events has been well recognized. Left ventricular (LV) dyssynchrony is a measure of regional myocardial dysfunction. Our objective was to investigate the relationship of subclinical atherosclerosis with mechanical LV dyssynchrony in a population-based asymptomatic multi-ethnic cohort.Participants of the Multi-Ethnic Study of Atherosclerosis (MESA) at exam 5 were evaluated using 1.5T cardiac magnetic resonance (CMR) imaging, carotid ultrasound (n = 2062) for common carotid artery (CCA) and internal carotid artery (ICA) intima-media thickness (IMT), and cardiac computed tomography (n = 2039) for coronary artery calcium (CAC) assessment (Agatston method). Dyssynchrony indices were defined as the standard deviation of time to peak systolic circumferential strain (SD-TPS) and the difference between maximum and minimum (max-min) time to peak strain using harmonic phase imaging in 12 segments (3-slices × 4 segments). Multivariable regression analyses were performed to assess associations after adjusting for participant demographics, cardiovascular risk factors, LV mass, and ejection fraction. In multivariable analyses, SD-TPS was significantly related to measures of atherosclerosis, including CCA-IMT (8.7 ms/mm change in IMT, p = 0.020), ICA-IMT (19.2 ms/mm change in IMT, p < 0.001), carotid plaque score (1.2 ms/unit change in score, p < 0.001), and log transformed CAC+1 (0.66 ms/unit log-CAC+1, p = 0.018). These findings were consistent with other parameter of LV dyssynchrony i.e. max-min.In the MESA cohort, measures of atherosclerosis are associated with parameters of subclinical LV dyssynchrony in the absence of clinical coronary event and left-bundle-branch block.
Project description:BACKGROUND: Right ventricular (RV) pacing generates regional disparities in electrical activation and mechanical function (ventricular dyssynchrony). In contrast, left ventricular (LV) or biventricular (BIV) pacing can improve cardiac efficiency in the setting of ventricular dyssynchrony, constituting the rationale for cardiac resynchronization therapy (CRT). Animal models of ventricular dyssynchrony and CRT currently relay on large mammals which are expensive and not readily available to most researchers. We developed a methodology for double-site epicardial pacing in conscious rats. Here, following post-operative recovery, we compared the effects of various pacing modes on LV dyssynchrony in normal rats and in rats with ischemic cardiomyopathy. METHODS: Two bipolar electrodes were implanted in rats as follows: Group A (n = 6) right atrial (RA) and RV sites; Group B (n = 7) RV and LV sites; Group C (n = 8) as in group B in combination with left coronary artery ligation. Electrodes were exteriorized through the back. Following post-operative recovery, two-dimensional transthoracic echocardiography was performed during pacing through the different electrodes. Segmental systolic circumferential strain (Ecc) was used to evaluate LV dyssynchrony. RESULTS: In normal rats, RV pacing induced marked LV dyssynchrony compared to RA pacing or sinus rhythm, as measured by the standard deviation (SD) of segmental time to peak Ecc, SD of peak Ecc, and the average delay between opposing ventricular segments. LV pacing and, to a greater extend BIV pacing diminished the LV dyssynchrony compared to RV pacing. In rats with extensive MI, the effects of LV and BIV pacing were markedly attenuated, and the response of individual animals was variable. CONCLUSIONS: Rodent cardiac pacing mimics important features seen in humans. This model may be developed as a simple new tool to study the pathophysiology of ventricular dyssynchrony and CRT.
Project description:Background: Coronary artery dissection (CAD) sometimes accompanies unstable hemodynamics and requires mechanical cardiac support. Meanwhile, mechanical cardiac support may influence coronary hemodynamics in CAD. No study has examined the impact of Impella left ventricular (LV) support on CAD. Materials and Methods: CAD was induced in eight Yorkshire pigs by injuring the left anterior descending artery (LAD) using a 0.018-in. stiff guidewire and/or deep engagement of a blunt-cut coronary guiding catheter. After the creation of CAD, hemodynamic parameters, coronary pressure, and flow as well as coronary angiograms were acquired before and after maximum LV support using the Impella CP. Result: CADs with a large flap were successfully created by deep engagement of a blunt-tip guiding catheter with forceful contrast injection. One animal (#8) exhibited thrombolysis in myocardial infarction (TIMI)-1 flow, while the others (animals #1-#7) showed TIMI-2/3 flow. In TIMI-2/3 animals, maximal Impella support increased mean coronary pressure (108.4 ± 22.5 to 124.7 ± 28.0 mmHg, P < 0.001) with unchanged mean coronary flow velocity (63.50 ± 28.66 to 48.32 ± 13.30 cm/s, P = 0.17) of the LAD distal to the dissection. The LV end-diastolic pressure (20.6 ± 6.6 vs. 12.0 ± 3.4 mmHg, P = 0.032), LV end-diastolic volume (127 ± 32 vs. 97 ± 26 ml, P = 0.015), stroke volume (68 ± 16 vs. 48 ± 14 ml, P = 0.003), stroke work (5,744 ± 1,866 vs. 4,424 ± 1,650 mmHg·ml, P = 0.003), and heart rate (71.4 ± 6.6 vs. 64.9 ± 9.3/min, P = 0.014) were all significantly reduced by Impella support, indicating effective unloading of the LV. In the TIMI-1 animal (animal #8), maximal Impella support resulted in further delay in angiographic coronary flow and reduced distal coronary pressure (22.9-17.1 mmHg), together with increased false-lumen pressure. Conclusion: Impella support effectively unloaded the LV and maintained the hemodynamics in a novel porcine model of CAD. Coronary pressure distal to the dissection was increased in TIMI-2/3 animals after Impella support but decreased in the animal with initial TIMI-1 flow.
Project description:Coronary plaque distribution, frequency and cut-off value of percent stenosis for developing vasospasm are uncertain in patients with vasospastic angina (VA). We enrolled 2960 patients who received coronary angiography (CAG) and ergonovine provocation test prospectively in 11 university hospitals in Korea. A total of 1836 patients with VA and 867 without VA were included. Plaque and % stenosis were defined as ?1% luminal narrowing and mean of each segmental stenosis. Overall frequency of plaque and % diameter stenosis was compared among VA-patients with index coronary spasm positive, those with index arterial spasm negative/other arterial spasm positive (INOP) and non-VA patients. Diameter stenosis associated with the spasm positivity was investigated. Overall plaque frequency and % stenosis were higher in VA patients than non-VA patients. Plaque frequency was 27.6% (243/881) in spasm positive at LAD, 16.4% (157/955) in LAD INOP and 12.6% (109/867) in non-VA with statistic difference (P?<?0.001). Same trend for higher rate was observed in LCx and RCA. For % stenosis, 36.6 vs 32.4% (p?=?0.010) in LAD, 36.1 vs. 28% (p?<?0.001) in LCx and 35.3 vs.30.0% (p?=?0.047) in RCA, respectively. Diameter stenosis of LAD with spasm positive vs. LAD INOP vs. non-VA were 38.3%, 34.0%, 32% (P?=?0.002) with similar pattern in LCx and RCA. By multivariate logistic regression analysis, coronary stenosis of LAD???35% or LCx ?35% or RCA???40% were independent predictor of developing spasm (OR 2.019, 95% CI 1.315-3.100, P?=?0.001). In conclusions, spastic coronary artery had more plaque frequency, higher % stenosis than in non-spastic coronary in VA patients. The spasm related and unrelated coronary in VA patients had more plaque than in matched and unmatched coronary arteries in non-VA patients. Coronary stenosis ?35% in LAD and LCx was an independent predictor of developing spasm.
Project description:BACKGROUND:Dual-source computed tomography (CT) can evaluate left ventricular (LV) dyssynchrony, myocardial scar, and coronary venous anatomy in patients undergoing cardiac resynchronization therapy (CRT). OBJECTIVE:We aimed to determine whether dual-source CT predicts clinical CRT outcomes and reduces intraprocedural time. METHODS:In this prospective study, 54 patients scheduled for CRT (mean age 63 ± 11 years; 74% men) underwent preprocedural CT to assess their venous anatomy as well as CT-derived dyssynchrony metrics and myocardial scar. Based on 1:1 randomization, the implanting physician had preimplant knowledge of the venous anatomy in half the patients. In blinded analyses, we measured time to maximal wall thickness and inward wall motion to determine (1) CT global and segmental dyssynchrony and (2) concordance of lead location to regional LV mechanical contraction. End points were 6-month CRT response measured using heart failure clinical composite score and 2-year major adverse cardiac events (MACE). RESULTS:There were 72% CRT responders and 17% with MACE. Two wall motion dyssynchrony indices-global wall motion and opposing anteroseptal-inferolateral wall motion-predicted MACE (P < .01). Lead location concordant to regions of maximal wall thickness was associated with less MACE (P < .01). No CT dyssynchrony metrics predicted 6-month CRT response (P = NS for all). Myocardial scar (43%), posterolateral wall scar (28%), and total scar burden did not predict outcomes (P = NS for all). Preknowledge of coronary venous anatomy by CT did not reduce implant or fluoroscopy time (P = NS for both). CONCLUSION:Two CT dyssynchrony metrics predicted 2-year MACE, and LV lead location concordant to regions of maximal wall thickness was associated with less MACE. Other CT factors had little utility in CRT.
Project description:The aim of this study was to assess the accuracy of echocardiographic techniques in detecting the early recovery of left ventricular (LV) function after revascularization in acute coronary syndrome (ACS). In 80 consecutive patients with ACS (age 55.7 ± 9.4 years, 77% male, 15% with CCS Angina III), an echocardiographic examination of left ventricle regional wall motion abnormalities (LV RWMA), peak systolic strain rate (PSSR), peak systolic strain (PSS) and end systolic strain (ESS) was performed before and after percutaneous intervention (PCI). Of the 80 patients, one vessel stenosis (>70%) was present in 53 (66%), two vessel disease in 12 (15%) and multivessel disease in 15 patients (19%). In total, 51% of patients had hypertension, 40% diabetes and 23% dyslipidemia. After PCI, regional PSS, ESS and PSSR of their segments subtended by the culprit vessel improved; left anterior descending-LAD, circumflex-LCx and right coronary-RCA (p<0.05 for all) as well as global S and SR (p < 0.05 for all). In univariate analysis, hypertension (HTN) (? = -0.294 (-0.313-0.047), p = 0.009, smoking ? = -0.244 (-0.289-0.015) =0.03, WMA ? = -0.317 (-0.284-0.014), p = 0.004 and the number of diseased vessels ? = -0.256 (-0.188- 0.054) p=0.03 were predictors of delta global SR. In multivariate analysis, only HTN ? = 0.263 (0.005-3.159) and the number of diseased vessels ? =0.263 (0.005 - 3.159), p=0.04) predicted delta global SR. In ACS, the echocardiographic regional myocardial deformation is accurate in detecting early recovery of LV myocardial function after culprit lesion revascularization. Also, the findings of this study support the current practice regarding the crucial importance of proximal epicardial vessel PCI treatment on LV function compared to more distal lesions.