Yoshiharu Enomoto

Validation of 3-Dimensional Speckle Tracking Imaging to Quantify Regional Myocardial Deformation

Background—Three-dimensional speckle tracking imaging (3D-STI) has been introduced to assess regional left ventricular (LV) myocardial function. This study was designed to validate LV strain measurements by 3D-STI against data obtained by sonomicrometry. Methods and Results—In each of 10 anesthetized sheep, sonomicrometry crystals were implanted on the endocardium and epicardium at the LV basal, mid, and apical anterior and lateral walls. LV 3D-STI data sets were obtained from the apical approach at a frame rate of approximately 30 frames/s. Segmental longitudinal (LS), radial (RS), and circumferential strain (CS) measurements by 3D-STI were compared with those by sonomicrometry at baseline and during pharmacological stress tests (dobutamine and propranolol infusion) and acute myocardial ischemia induced by coronary artery occlusion. Data were available from 136 LS, 108 CS, and 175 RS measurements. Good correlations were observed between strain measurements by 3D-STI and those by sonomicrometry (LS: r=0.89, P<0.001; RS: r=0.84, P<0.001; CS: r=0.90, P<0.001). In each segmental study, significant correlations of the 3 strain components were observed (LS: r=0.65 to 0.68, P<0.001; RS: r=0.59 to 0.70, P<0.001; CS: r=0.71 to 0.78, P<0.001). Conclusions—The newly developed 3D-STI technique can estimate LV regional circumferential, longitudinal, and radial strain components with reasonable correlation to sonomicrometry data. This methodology could be applied clinically to assess alteration of myocardial function by accurately measuring strain in basal, mid, and apical LV segments, even during pharmacological and ischemic interventions. Therefore, 3D-STI appears to be a reliable tool to assess LV regional wall function.

Annuloplasty ring selection for chronic ischemic mitral regurgitation: lessons from the ovine model.

BACKGROUND Chronic ischemic mitral regurgitation (CIMR) is poorly understood and repair operations are often unsatisfactory. This study elucidates the mechanism of CIMR in an ovine model. METHODS Sonomicrometry array localization measured the three-dimensional geometry of the mitral annulus and subvalvular apparatus in five sheep before and 8 weeks after a posterior infarction of the left ventricle that produced progressive severe CIMR. RESULTS End systolic annular area increased from 647 +/- 44 mm(2) to 1,094 +/- 173 mm(2) (p = 0.01). Annular dilatation occurred equally along the anterior (47.0 +/- 5.6 mm to 60.2 +/- 4.9 mm, p = 0.001) and posterior (53.8 +/- 3.1 mm to 68.5 +/- 8.4 mm, p = 0.005) portions of the annulus. The tip of the anterior papillary muscle moved away from both the anterior and posterior commissures by 5.2 +/- 3.2 mm (p = 0.021) and 7.3 +/- 2.2 mm (p = 0.002), respectively. The distance from the tip of the posterior papillary muscle to the anterior commissure increased by 11.0 +/- 5.7 mm (p = 0.032) while the distance from the tip of the posterior papillary muscle to the posterior commissure remained constant. CONCLUSIONS Progressive dilatation of both the anterior and posterior mitral annuli, increased annular area, and asymmetric ventricular dilatation combine to cause CIMR by distortion of mitral valve geometry and tethering of leaflet coaptation. Therefore complete ring annuloplasty may be superior to partial annuloplasty in the treatment of CIMR.

The effect of regional ischemia on mitral valve annular saddle shape.

BACKGROUND The mitral valve annulus has a distinctive saddle shape. Recent finite element analysis indicates this shape may contribute to normal valve function by increasing leaflet curvature and reducing leaflet stress. This study tests the hypothesis that acute ischemic mitral regurgitation (AIMR) is associated with loss of annular saddle shape. METHODS Sonomicrometry array localization (SAL) measured the three-dimensional geometry of the mitral annulus in 6 sheep before and after 30 min of posterior ischemia that produced severe AIMR. Using this SAL data the annular height to commissural width ratio (AHCWR), a measure of annular saddle shape, was calculated throughout the cardiac cycle and reported as a percentage. RESULTS The normal mitral annulus accentuated its saddle shape rapidly during isovolemic contraction: AHCWR increased from 11.6% +/- 1.1%-13.9% +/- 1.6% (p < 0.001). During ejection AHCWR remained relatively constant ranging from a minimum of 14.1% +/- 1.5% to a maximum of 14.9% +/- 1.3%. During ischemia AHCWR was found to be significantly smaller (p < 0.05) during isovolemic contraction, ejection, and isovolemic relaxation, but not during diastolic filling. Whereas ischemia did not affect AHCWR at end diastole (11.6% +/- 2.8%), the isovolemic accentuation of the saddle shape was lost. CONCLUSIONS The normal mitral annulus accentuates its saddle shape during systole. This accentuation is eliminated during ischemia that causes AIMR. These data suggest an association between annular saddle shape and valve competency.

Endocardial surface area tracking for assessment of regional LV wall deformation with 3D speckle tracking imaging.

OBJECTIVES The aim of this experimental study was to validate area tracking by 3-dimensional (3D) speckle tracking imaging (STI) as a method to measure changes in regional left ventricular (LV) endocardial surface area with sonomicrometry and to assess the usefulness as a wall motion evaluation method compared with 1-dimensional strain parameters. BACKGROUND A 3D-STI allows for tracking a regional endocardial surface area during a cardiac cycle. Area tracking is a new concept that regional wall motion is quantified through the magnitude of deformation in an endocardial surface area. METHODS In each of 8 anesthetized sheep, sonomicrometry crystals were implanted on the endocardium at the LV mid and apical anterior walls. Area change ratio (ACR) that was a novel parameter obtained by area tracking was measured as percentage change in a segmental area during systole. Segmental longitudinal (LS) and circumferential strain (CS) also were measured by 3D-STI. The ACR, LS, and CS were compared with those by sonomicrometry at baseline and during pharmacological stress tests (dobutamine and propranolol infusion) and acute myocardial ischemia induced by occlusion of mid-left ascending artery. RESULTS The strong correlation was observed between ACR measurements by 3D-STI and those by sonomicrometry (Y = -4.20 + 0.84X, r = 0.87, p < 0.001). The ACR showed significant relations with both LS and CS (LS: Y = -15.1 + 1.73X, r = 0.73, p < 0.001; CS: Y = -5.85 + 1.06X, r = 0.79, p < 0.001). ACR showed significant differences among baseline, pharmacological stress, and acute myocardial ischemia. In contrast, LS and CS were reduced significantly during acute ischemia studies compared with those during the other studies; no differences were observed among baseline, propranolol infusion, and dobutamine infusion studies. CONCLUSIONS Area tracking by 3D-STI can estimate changes in LV regional area and might be promising for regional wall motion evaluations.

Experimental validation of left ventricular transmural strain gradient with echocardiographic two-dimensional speckle tracking imaging

AIMS To validate intramural strain measured by a speckle tracking imaging (STI) system against that measured by sonomicrometry crystals. METHODS AND RESULTS In 11 anaesthetized sheep, six sets of three sonomicrometry crystals were implanted in endo-, mid-wall, and epimyocardium on the anterior and lateral walls. Circumferential strain (CS) was calculated at three layers from endo-, mid-wall, and epicardial speckle. Radial strain (RS) was assessed for inner and outer halves of the myocardium. We compared ultrasound-derived strain measurements against those by sonomicrometry at baseline and during pharmacological stress and coronary occlusion. Intraclass correlation coefficients at baseline and during coronary occlusion were as follows: endocardial CS 0.80, 0.97; mid-wall CS 0.58, 0.89; epicardial CS 0.71, 0.81; endocardial RS 0.50, 0.78; epicardial RS 0.35, 0.83; and total RS 0.33, 0.71; respectively. At baseline, endocardial strains were higher than mid-wall and epicardial strains, resulting in an inner/outer wall RS gradient and inner/mid/outer wall CS gradients. Ischaemia caused significant reduction in all strains and disappearance of the strain gradient. CONCLUSION A newly developed STI system can accurately assess the intramural heterogeneity of CS distribution in normal and ischaemic myocardial segments and has the potential to become a non-invasive bedside tool for characterizing myocardial strain gradient.

The minimum coronary artery diameter in which coronary spasm can be identified by synchrotron radiation coronary angiography

BACKGROUND Coronary vasospasm is defined as a temporary, intense narrowing of the coronary conduit artery. It brings about ischemic chest pain and becomes one of the causes of myocardial infarction. Coronary spasms are divided into two categories. One is the coronary spasm of the conduit artery and the other is the coronary microvascular spasm. Although coronary spasms are diagnosed with the images of coronary angiography, microvascular spasms cannot be diagnosed because of the limitations of conventional angiographic systems. However, synchrotron radiation coronary angiography (SRCA) can identify coronary arteries down to 100 microm in diameter in the beating heart and 50 microm in arrested heart. AIM The purpose of this study was to confirm whether microvascular spasms could be identified or not using SRCA, and then down that size identification was possible. METHODS The Langendorff perfusion system with isolated rat hearts was employed. Krebs-Henseleit solution (KH solution) was used as a perfusate. 10mM of 4-aminopyridine (4-AP: a voltage-gated potassium channel blocker; spasm inducer) was added to the KH solution and maintained for 5 min. SRCA was performed at pre-, during and 10 min after cessation of the KH solution with 4-AP. Coronary spasms were defined as a temporal 75% reduction of coronary arterial diameter. RESULTS AND CONCLUSION Multiple sizes of coronary arteries showed coronary spasms. The minimum stenosed coronary artery size was 100 microm. Since coronary microvascular spasms are seen in the arterioles (50-400 microm), coronary microvascular spasms may be diagnosed with the use of synchrotron radiation coronary angiography.

Activated neutrophils and platelet microaggregates impede blood filterability through microchannels during simulated extracorporeal circulation

BACKGROUND Neutrophil sequestration and platelet microaggregates in organ capillaries have been implicated in the inflammatory response associated with cardiopulmonary bypass. We examined the filterability of neutrophils and platelet microaggregates through silicon microchannels during simulated extracorporeal circulation. We hypothesize that blood contact with artificial surfaces over time decreases the ability of neutrophils, platelets, and their aggregates to pass through microchannels. METHODS Fresh human blood from donors (n = 9) was recirculated for 120 minutes in a simulated extracorporeal circuit. Blood samples were obtained from a donor at 0, 30, 60, and 120 minutes of recirculation. The microchannel transit time and the flow behavior of blood cells were evaluated by a silicon microchannel array flow analyzer. CD11b, L-selectin, and F-actin of neutrophils were measured by flow cytometry. Neutrophil and platelet counts and platelet aggregation to adenosine diphosphate were measured. RESULTS The microchannel transit time was prolonged during recirculation, reaching 185.9% +/- 25.6% of baseline at 120 minutes. The video microscope showed that neutrophils and platelet microaggregates plugged the microchannels. CD11b, L-selectin, and F-actin levels changed significantly by 120 minutes. Platelet counts decreased and platelet aggregability was attenuated. CONCLUSIONS Simulated extracorporeal circulation caused a progressive loss in the ability of neutrophils, platelets, and their aggregates to pass through the microchannels independent of neutrophil adhesion molecule expression.

ONO-6818, a novel, potent neutrophil elastase inhibitor, reduces inflammatory mediators during simulated extracorporeal circulation

BACKGROUND Among the serine proteases, neutrophil elastase is a powerful cytotoxic enzyme and plays a pivotal role in the inflammatory response associated with cardiopulmonary bypass. This study assesses the effects of the specific inhibition of neutrophil elastase by a novel, potent, low-molecular-weight neutrophil elastase inhibitor, ONO-6818. We hypothesized that ONO-6818 reduces inflammatory mediators and modulates adhesion molecules and the deformability of neutrophils during simulated extracorporeal circulation. METHODS Simulated extracorporeal circulation was established by recirculating fresh heparinized (3.75 U/mL) human blood for 120 minutes in a membrane oxygenator and a roller pump with and without 1.0 micromol/L of ONO-6818 (n = 9 for control group, n = 7 for ONO-6818 group). The neutrophil adhesion molecules, CD11b and L-selectin, and the cytoplasmic F-actin of neutrophils were measured by flow cytometry. Neutrophil deformability was evaluated using simulated silicon microcapillaries. Neutrophil elastase, interleukin 8, and C5b-9 were measured using enzyme immunoassay. RESULTS Neutrophil elastase levels were significantly lower in the ONO-6818 group. ONO-6818 significantly reduced interleukin 8 and C5b-9 production. ONO-6818 did not modulate changes of CD11b and L-selectin during recirculation. Cytoplasmic F-actin content and changes of neutrophil deformability did not significantly differ between the groups. CONCLUSIONS Inhibition of neutrophil elastase activity with ONO-6818 reduces further interleukin 8 production and the formation of the complement membrane attack complex, and this results in a reduction of neutrophil elastase levels during simulated extracorporeal circulation. This study suggests that specific neutrophil elastase inhibition with ONO-6818 is a feasible therapeutic option to attenuate the exaggerated inflammatory response associated with cardiopulmonary bypass.

Complex coronary artery aneurysm

A 68-year-old female with no previous history of coronary artery disease, hypertension, or hyperlipidemia presented with abnormal electrocardiographic changes which was ST elevation in V1 and V2 lead. The electrocardiogramwas performed for regular medical checkup. An echocardiogram revealed an aneurysmal structure along the intraventricular septum (Figure 1A). A computed tomogram (CT) demonstrated a coronary artery aneurysm, 5.0 × 2.8 cm, with a 1.3 × 1.0-cm pseudoaneurysm (Figure 2A). A coronary angiogram revealed that the aneurysm appeared to arise from the left anterior descending (LAD) artery and was fed by a septal artery (Figure 1B). At the time of surgery, following institution of cardiopulmonary bypass and cardioplegic arrest, the feeding artery was identified and divided and each end closed with a running 6-0 polypropylene suture (Figure 3A). The aneurysm and pseudoaneurysm were opened and no fistulas or other vascular communications could be identified. The aneurysmal wall was obliterated with a running 3-0 prolene suture (Figure 3B). The patient tolerated the procedure and had no coronary ischemia. A postoperative CT scan showed a patent LAD without any aneurysmal changes (Figure 2B).

Leukocyte-Depleted Blood Cardioplegia Reduces Cardiac Troponin T Release in Patients Undergoing Coronary Artery Bypass Grafting

OBJECTIVE Activated neutrophils have been implicated in reperfusion injury of the myocardium. Leukocyte depletion at reperfusion may contribute to better myocardial protection during cardiac surgery. We tested the efficacy of leukocyte-depleted blood cardioplegia in reducing myocardial injury during coronary artery bypass grafting. METHODS Subjects were 27 patients undergoing elective coronary artery bypass grafting divided into controls (perfused with nonfiltered blood cardioplegia, n = 12) and those undergoing leukocyte-depleted blood cardioplegia (n = 15). Oxygenated blood mixed with a potassium crystalloid cardioplegic solution was delivered through the aortic root at every 30 minutes during cardiac arrest and terminal warm blood was administered before aortic declamping in both groups. In leukocyte depletion, blood was filtered prior to the mixture with crystalloid solution in the cardioplegic reservoir. RESULTS Patient profiles did not differ significantly between groups, nor did systemic leukocyte count during or after surgery despite more than 81% removal of leukocytes in cardioplegic delivery. No consistent differences between groups in creatine kinase or creatine kinase-MB were seen up to 18 hours after surgery. Peak troponin T levels were significantly lower in the leukocyte-depleted blood cardioplegia group (0.52 +/- 0.13 ng/ml), however, than in controls (3.85 +/- 0.85 ng/ml). CONCLUSION We concluded that leukocyte-depleted blood cardioplegia reduces the release of cardiac troponin T in patients undergoing elective coronary artery bypass grafting and may produce better myocardial protection in patients with impaired cardiac function or a damaged myocardium.