Kunihiko Nagai

Pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus: an intravascular ultrasound scanning study

BACKGROUND It has been reported that pioglitazone reduces neointimal hyperplasia after balloon-induced vascular injury in an experimental model. METHODS To determine whether pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus, we studied 44 stented lesions in 44 patients with diabetes mellitus who underwent successful coronary stent implantation. Study patients were randomized into 2 groups: the pioglitazone group (23 patients with 23 lesions) and the control group (21 patients with 21 lesions). All patients underwent serial quantitative coronary angiography and serial intravascular ultrasound scanning studies. With a motorized pullback system, multiple image slices within the stent were obtained at every 1 mm. The stent area and lumen area were measured, and the neointimal area was calculated. Measurements were averaged over the number of selected image slices. The neointimal index was calculated as the averaged neointimal area divided by the averaged stent area multiplied by 100 (%). RESULTS After 6 months of treatment, angiographic in-stent restenosis (17% vs 43%, respectively, P =.0994) and target lesion revascularization (13% vs 38%, respectively, P =.0835) were less frequent in the pioglitazone group than the control group; however, these differences did not reach significance. The intravascular ultrasound scanning study demonstrated that the neointimal index in the pioglitazone group was significantly smaller than that in the control group (28% +/- 9% vs 48% +/- 15%, respectively, P <.0001). CONCLUSION A serial intravascular ultrasound scanning assessment demonstrated that pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus.

Annular Geometry in Patients With Chronic Ischemic Mitral Regurgitation: Three-Dimensional Magnetic Resonance Imaging Study

Background—Although animal studies showed that annular remodeling may be related to the pathogenesis of chronic ischemic mitral regurgitation (CIMR), little was known in humans. A better understanding of the precise 3D geometry of the mitral valvular-ventricular complex in CIMR is needed to devise a better surgical technique. The purpose of the study was to elucidate mitral annular geometry in patients with CIMR using cardiac MRI. Methods and Results—Thirty-eight patients with previous inferior or posterior myocardial infarction were studied. With the 3D reconstruction of the mitral annulus and subvalvular apparatus from a series of longitudinal cine MRIs, end-systolic mitral annulus dimensions and 3D geometry were calculated. Patients were grouped by mitral regurgitation grade using echocardiography (≥2+, n=15 versus ≤1+, n=23). Both septal-lateral and commissure-commissure mitral annular diameters were significantly greater in CIMR(+) patients (35±5 versus 30±4 mm, P=0.005; 46±6 versus 39±4 mm, P<0.001, respectively). The length of the fibrous annulus was significantly larger in CIMR(+) patients (28±3 versus 24±3 mm; P<0.001). The height of the annular “saddle horn” above a best-fit plane was lower in CIMR(+) patients (4.2±1.2 versus 6.0±1.8 mm; P=0.002), and the annular height to commissural width ratio was significantly lower in CIMR(+) patients (12±3 versus 21±5%; P<0.001). Conclusions—Patients with CIMR had greater septal-lateral and commissure-commissure mitral annular dimension, larger intertrigonal distance, and flattened saddle shape of mitral annulus. These associated geometric alterations may be important in the pathogenesis of CIMR.

Inhibition of Sarcolemmal Na+,K+-ATPase Activity Reduces the Infarct Size–Limiting Effect of Preconditioning in Rabbit Hearts

BACKGROUND The inhibition of sarcolemmal Na+,K+-ATPase activity is closely related to ischemic myocardial cell injury. However, the involvement of this enzyme in preconditioning has not been determined. METHODS AND RESULTS We assessed the effect of ischemia on sarcolemmal Na+,K+-ATPase activity. Control and preconditioned rabbits were subjected to 0, 10, 20, 30, and 60 minutes of coronary occlusion. Ten to 60 minutes of ischemia reduced Na+,K+-ATPase activity, whereas preconditioning preserved the activity of this enzyme only during the first 20 minutes of ischemia. To determine whether the preservation of Na+,K+-ATPase activity in the early phase of ischemia contributed to limiting the infarct size, additional rabbits underwent 30 minutes of occlusion followed by 3 hours of reperfusion with or without pretreatment with digoxin, an inhibitor of Na+,K+-ATPase. Infarct size in animals pretreated with digoxin in the absence of preconditioning did not differ from that in controls. It was markedly reduced by preconditioning, whereas digoxin reduced the infarct size-limiting effect. Moreover, preconditioning increased sarcolemmal Na+-Ca2+ exchange activity in rabbits subjected to 20 minutes of ischemia, whereas digoxin diminished this increase. CONCLUSIONS Preconditioning preserves the ischemia-induced reduction in sarcolemmal Na+,K+-ATPase activity in the early phase of ischemia in rabbit hearts. Inhibition of Na+,K+-ATPase activity reduces the infarct size-limiting effect of preconditioning with a loss of increased Na+-Ca2+ exchange activity, implying that this preservation is responsible for the cardioprotective effect of preconditioning.

Ischemic preconditioning is associated with a delay in ischemia-induced reduction of beta-adrenergic signal transduction in rabbit hearts.

BackgroundIt has been reported that the A,-adenosine receptor mediates the cardioprotective effect of ischemic preconditioning. This receptor couples inhibitory guanine nucleotide-binding protein (Gi) and inhibits adenylate cyclase activity. However, the role of adenylate cyclase in preconditioning is unknown. Methods and ResultsWe compared the effects of ischemia on the sarcolemmal I3-adrenergic receptor density (Bm.), the stimulatory guanine nucleotide-binding protein (G,) activity as determined by reconstitution with S49 lymphoma cyc- membranes, and baseline and maximally stimulated adenylate cyclase activities (ACAs) in control and preconditioned rabbit hearts. The control population (n=28) received 0, 10, 20, and 60 minutes of coronary occlusion (n=6 to 8 per stage), and preconditioned rabbits (n=24) received two cycles of alternating 5-minute occlusion and reperfusion before sustained ischemia (n=6 per stage). In control hearts, occlusion induced rapid and progressive reductions in the B.., G, and ACAs after 10 to 60 minutes of ischemia. Preconditioning did not affect the reduction in B.., but it preserved reductions in G, activity and ACAs after 10 to 20 but not 60 minutes of sustained ischemia. In another study, 18 rabbits were treated with pertussis toxin 48 hours before surgery to block Gi. During treatment, no significant difference was observed in the ischemia-induced reduction in ACAs in the ischemic region between control (n=8) and preconditioned (n=10) animals after 20 minutes of ischemia. ConclusionPreconditioning delays ischemia-induced reductions in 3-adrenergic signal transduction. Inhibition of ACA is not the target effect of the A1-adenosine receptor-Gi pathway responsible for the cardioprotective role of preconditioning.

Quantitative assessment of harmonic power doppler myocardial perfusion imaging with intravenous levovist™ in patients with myocardial infarction: comparison with myocardial viability evaluated by coronary flow reserve and coronary flow pattern of infarct-related artery

BackgroundMyocardial contrast echocardiography and coronary flow velocity pattern with a rapid diastolic deceleration time after percutaneous coronary intervention has been reported to be useful in assessing microvascular damage in patients with acute myocardial infarction.AimTo evaluate myocardial contrast echocardiography with harmonic power Doppler imaging, coronary flow velocity reserve and coronary artery flow pattern in predicting functional recovery by using transthoracic echocardiography.MethodsThirty patients with anterior acute myocardial infarction underwent myocardial contrast echocardiography at rest and during hyperemia and were quantitatively analyzed by the peak color pixel intensity ratio of the risk area to the control area (PIR). Coronary flow pattern was measured using transthoracic echocardiography in the distal portion of left anterior descending artery within 24 hours after recanalization and we assessed deceleration time of diastolic flow velocity. Coronary flow velocity reserve was calculated two weeks after acute myocardial infarction. Left ventricular end-diastolic volumes and ejection fraction by angiography were computed.ResultsPts were divided into 2 groups according to the deceleration time of coronary artery flow pattern (Group A; 20 pts with deceleration time ≧ 600 msec, Group B; 10 pts with deceleration time < 600 msec). In acute phase, there were no significant differences in left ventricular end-diastolic volume and ejection fraction (Left ventricular end-diastolic volume 112 ± 33 vs. 146 ± 38 ml, ejection fraction 50 ± 7 vs. 45 ± 9 %; group A vs. B). However, left ventricular end-diastolic volume in Group B was significantly larger than that in Group A (192 ± 39 vs. 114 ± 30 ml, p < 0.01), and ejection fraction in Group B was significantly lower than that in Group A (39 ± 9 vs. 52 ± 7%, p < 0.01) at 6 months. PIR and coronary flow velocity reserve of Group A were higher than Group B (PIR, at rest: 0.668 ± 0.178 vs. 0.248 ± 0.015, p < 0.0001: during hyperemia 0.725 ± 0.194 vs. 0.295 ± 0.107, p < 0.0001; coronary flow velocity reserve, 2.60 ± 0.80 vs. 1.31 ± 0.29, p = 0.0002, respectively).ConclusionThe preserved microvasculature detecting by myocardial contrast echocardiography and coronary flow velocity reserve is related to functional recovery after acute myocardial infarction.

Chronic dynamic exercise improves a functional abnormality of the G stimulatory protein in cardiomyopathic BIO 53.58 Syrian hamsters.

BackgroundThe effects of chronic exercise training on myocardial contractility and β-adrenergic signal transduction in hearts with left ventricular dysfunction have not been determined. Methods and ResultsFourteen-week-old cardiomyopathic BIO 53.58 and normal F1B Syrian hamsters underwent 10 weeks of treadmill training and were compared with 24-weekold BIO 53.58 and F1B untrained controls. Left ventricular isovolumic maximum positive dP/dt and peak developed pressure were significantly lower in BIO 53.58 than in F1B controls. Exercise training improved left ventricular contractile indices in BIO 53.58 but not F1B hamsters. The left ventricular β-adrenergic receptor number (Bmax) was similar in BIO 53.58 and F1B controls. Basal adenylate cyclase activity (ACA) and ACAs stimulated by isoproterenol, 5′-guanylylimidodiphosphate (GppNHp), sodium fluoride, and forskolin were significantly lower in BIO 53.58 than in F1B controls. The functional activity of stimulatory guanine nucleotide-binding protein (Gs), as determined by reconstitution with S49 lymphoma cyc− cell membranes, was significantly lower in BIO 53.58 controls. After 10 weeks of exercise training, Bmax and basal and isoproterenol-stimulated ACAs were unchanged in either BIO 53.58 or F1B hamsters compared with controls. However, in F1B hamsters, training decreased ACAs stimulated by GppNHp, sodium fluoride, and forskolin, with a reduced functional activity of Gs In contrast, these ACAs increased significantly in association with an enhanced G, activity in cardiomyopathic BIO 53.58 hamsters after training. ConclusionsChronic exercise training does not change receptor-mediated β-adrenergic responsiveness in either F1B or BIO 53.58 hamsters. However, exercise training reduces Gs activity in normal F1B hamsters and improves the functional abnormality of Gs in cardiomyopathic BIO 53.58 hamsters. This improvement may potentially contribute to augmented left ventricular contractility in BIO 53.58 after training.

1037-144 Left atrial volume and the risk of paroxysmal atrial fibrillation in patients with hypertrophic cardiomyopathy

Paroxysmal atrial fibrillation (PAF) is a common complication of patients with hypertrophic cardiomyopathy (HCM), often leading to acute or progressive heart failure and cerebral infarction. Therefore, the early detection of patients with HCM at risk for atrial fibrillation (AF) development has important implications for patient treatment. M-mode left atrial (LA) dimension, a unidimensional measure of LA size, was shown to be incremental to clinical risk factors for predicting AF in both the Framingham Heart Study and the Cardiovascular Health Study. However, the inaccuracy of the M-mode method is expected when the LA enlarges, and LA volume (LAV) has been shown to provide a more accurate assessment of LA size than M-mode LA dimensions. The aim of this study was to evaluate the ability of LAV to assess the risk of PAF development for patients with HCM and preserved left ventricular (LV) systolic function.

1157-43 Coronary flow velocity pattern immediately after percutaneous coronary intervention as a predictor of complications after acute myocardial infarction in patients achieving thrombolysis in myocardial infarction grade 3 flow

Background: Strokes are particularly devasting to the African American community and extracranial carotid artery disease is a significant etiologic factor. The benefits of surgical intervention with carotid endarterectomy are well documented, but African Americans are underrepresented in most of these trials and there is evidence that their post surgical short-term mortality is increased. Carotid artery stenting(CAS) is rapidly becoming an accepted treatment strategy for certain high risk patient groups and this study examines the safety and efficacy of CAS in African Americans. Methods: Between December 1999 and August 2003, a total of 172 consecutive patients underwent CAS. Patients were objectively evaluated preand post procedure by a board certified neurologist and NIH stroke scores were recorded. All cases were performed by a single operator in a single institution. All patients received periprocedural intravenous IIB/IIIA inhibitors and fractionated heparin to maintain activated clotting time (ACT) 200-250 secs. All cases were performed without distal protection. All patients received oral antiplatelet therapy for at least 4 weeks post procedure. Results: In a retrospective review of the 172 patients, 66(38%) were African Americans. Of this group, there was a 100 % procedural success rate. There were no periprocedural major or minor strokes. There were no TIAs. There were no significant change in pre-and post procedural NIH stroke scores. There were no deaths. At 30 days there were no new neurovascular events or deaths. Conclusion: CAS is a safe and efficacious procedure in the managemnet of extracranial cerobrovascular disease in African Americans.

Noninvasive assessment of flow velocity and flow velocity reserve in the right gastroepiploic artery graft by transcutaneous Doppler echocardiography: comparison with an invasive technique.

BACKGROUND The measurement of flow velocity (FV) in coronary artery bypass grafts using a Doppler guidewire has provided useful clinical and physiologic information. The recently developed transcutaneous Doppler echocardiography is a noninvasive technique to measure FV and FV reserve (FVR) in the right gastroepiploic artery (GEA) graft. The purpose of this study was to evaluate whether transcutaneous Doppler echocardiography accurately measures FV and FVR in the right GEA graft in a clinical setting. METHODS In 33 patients who underwent graft angiography for the assessment of the right GEA graft, FV in the right GEA graft was measured by transcutaneous Doppler echocardiography under the guidance of color flow Doppler imaging at the time of examination using a Doppler guidewire. FV in the midportion of the right GEA graft was measured at baseline and during hyperemic conditions using both transcutaneous Doppler echocardiography and a Doppler guidewire. RESULTS There were excellent correlations between the value of FV obtained by transcutaneous Doppler echocardiography and those obtained with the Doppler guidewire (averaged peak velocity: y = 0.95 x + 1.46, r = 0.98, standard error of the estimate [SEE] = 2.94 cm/s; averaged systolic peak velocity: y = 0.94 x + 1.18, r = 0.97, SEE = 3.15 cm/s; diastolic peak velocity: y = 0.97 x + 1.62, r = 0.98, SEE = 4.40 cm/s; averaged diastolic peak velocity: y = 0.95 x + 1.75, r = 0.98, SEE = 3.60 cm/s). The FVR as determined by transcutaneous Doppler echocardiography showed a good correlation with that determined using the Doppler guidewire method (y = 0.90 x + 0.21, r = 0.92, SEE = 0.31). CONCLUSIONS Transcutaneous Doppler echocardiography proved to be an accurate noninvasive method to measure FV and FVR in the right GEA graft.

Identification of Cardiac Abnormal Structures with Harmonic Power Doppler Contrast Echocardiography

We describe two cases in which echocardiographic image enhancement with an intravenous contrast agent using harmonic power Doppler (HPD) imaging established the diagnosis of abnormal structures in the left ventricle (LV).