Congenital hearing impairment associated with peripheral cochlear nerve dysmyelination in glycosylation-deficient muscular dystrophy.

Hearing loss (HL) is one of the most common sensory impairments and etiologically and genetically heterogeneous disorders in humans. Muscular dystrophies (MDs) are neuromuscular disorders characterized by progressive degeneration of skeletal muscle accompanied by non-muscular symptoms. Aberrant glycosylation of α-dystroglycan causes at least eighteen subtypes of MD, now categorized as MD-dystroglycanopathy (MD-DG), with a wide spectrum of non-muscular symptoms. Despite a growing number of MD-DG subtypes and increasing evidence regarding their molecular pathogeneses, no comprehensive study has investigated sensorineural HL (SNHL) in MD-DG. Here, we found that two mouse models of MD-DG, Largemyd/myd and POMGnT1-KO mice, exhibited congenital, non-progressive, and mild-to-moderate SNHL in auditory brainstem response (ABR) accompanied by extended latency of wave I. Profoundly abnormal myelination was found at the peripheral segment of the cochlear nerve, which is rich in the glycosylated α-dystroglycan-laminin complex and demarcated by "the glial dome." In addition, patients with Fukuyama congenital MD, a type of MD-DG, also had latent SNHL with extended latency of wave I in ABR. Collectively, these findings indicate that hearing impairment associated with impaired Schwann cell-mediated myelination at the peripheral segment of the cochlear nerve is a notable symptom of MD-DG.

Cervical abscess caused by Mycobacterium tilburgii in a patient carrying anti-interferon gamma autoantibody: A case report and literature review.

Mycobacterium tilburgii, a nonculturable mycobacterium, is an important nontuberculous mycobacterium that occasionally causes serious infections in patients with cellular immune deficiencies. Due to its nonculturable nature, information about its drug susceptibility is not available, and data about its clinical response to antimycobacterial treatment remains insufficient. Here, we report a case of a patient who presented with neck swelling and was finally diagnosed with cervical abscess caused by M. tilburgii carrying anti-interferon gamma autoantibodies using a molecular method. The relevant literature was reviewed in the context of epidemiological and clinical data on M. tilburgii infections. In this report, 15 patients were reported to be infected with M. tilburgii. Almost all patients had a cellular immune deficiency and presented with disseminated infections. Multiple refractory or relapse cases that often required prolonged antimycobacterial treatment have been reported, although a few fatal cases have also been reported. In conclusion, M. tilburgii is an important pathogen in patients with cellular immune deficiency. Physicians should thoroughly investigate cellular immune deficiency, including adult-onset immune deficiency with anti-interferon gamma autoantibodies, in patients with M. tilburgii infection.

Hearing vulnerability after noise exposure in a mouse model of reactive oxygen species overproduction.

Previous studies have convincingly argued that reactive oxygen species (ROS) contribute to the development of several major types of sensorineural hearing loss, such as noise-induced hearing loss (NIHL), drug-induced hearing loss, and age-related hearing loss. However, the underlying molecular mechanisms induced by ROS in these pathologies remain unclear. To resolve this issue, we established an in vivo model of ROS overproduction by generating a transgenic (TG) mouse line expressing the human NADPH oxidase 4 (NOX4, NOX4-TG mice), which is a constitutively active ROS-producing enzyme that does not require stimulation or an activator. Overproduction of ROS was detected at the cochlea of the inner ear in NOX4-TG mice, but they showed normal hearing function under baseline conditions. However, they demonstrated hearing function vulnerability, especially at high-frequency sounds, upon exposure to intense noise, which was accompanied by loss of cochlear outer hair cells (OHCs). The vulnerability to loss of hearing function and OHCs was rescued by treatment with the antioxidant Tempol. Additionally, we found increased protein levels of the heat-shock protein 47 (HSP47) in models using HEK293 cells, including H2 O2 treatment and cells with stable and transient expression of NOX4. Furthermore, the up-regulated levels of Hsp47 were observed in both the cochlea and heart of NOX4-TG mice. Thus, antioxidant therapy is a promising approach for the treatment of NIHL. Hsp47 may be an endogenous antioxidant factor, compensating for the chronic ROS overexposure in vivo, and counteracting ROS-related hearing loss.

Maintenance of stereocilia and apical junctional complexes by Cdc42 in cochlear hair cells.

Cdc42 is a key regulator of dynamic actin organization. However, little is known about how Cdc42-dependent actin regulation influences steady-state actin structures in differentiated epithelia. We employed inner ear hair-cell-specific conditional knockout to analyze the role of Cdc42 in hair cells possessing highly elaborate stable actin protrusions (stereocilia). Hair cells of Atoh1-Cre;Cdc42(flox/flox) mice developed normally but progressively degenerated after maturation, resulting in progressive hearing loss particularly at high frequencies. Cochlear hair cell degeneration was more robust in inner hair cells than in outer hair cells, and began as stereocilia fusion and depletion, accompanied by a thinning and waving circumferential actin belt at apical junctional complexes (AJCs). Adenovirus-encoded GFP-Cdc42 expression in hair cells and fluorescence resonance energy transfer (FRET) imaging of hair cells from transgenic mice expressing a Cdc42-FRET biosensor indicated Cdc42 presence and activation at stereociliary membranes and AJCs in cochlear hair cells. Cdc42-knockdown in MDCK cells produced phenotypes similar to those of Cdc42-deleted hair cells, including abnormal microvilli and disrupted AJCs, and downregulated actin turnover represented by enhanced levels of phosphorylated cofilin. Thus, Cdc42 influenced the maintenance of stable actin structures through elaborate tuning of actin turnover, and maintained function and viability of cochlear hair cells.

Experiences of Percutaneous Endoscopic Approach for the Mastoid Lesions: A Novel Minimally Invasive Ear Surgery.

OBJECTIVES: We developed a novel keyhole surgery, named "percutaneous endoscopic ear surgery" (PEES), with the aim of further reducing the invasiveness of otologic surgery. We reported the cases we encountered and retrospectively analyzed the invasiveness of PEES. METHODS: We analyzed the ears of eight patients who underwent PEES for mastoid lesions that could not be manipulated with transcanal endoscopic ear surgery (TEES) at our hospital between July 2021 and November 2022. We performed PEES alone in three patients, including one case of type A (preauricular incision) and two cases of type B (retroauricular incision). The last five patients underwent combined endoscopic ear surgery, which is simultaneous PEES and TEES. In these cases, one patient underwent type A PEES, and four patients underwent type B PEES. RESULTS: PEES was performed in all patients without converting to conventional microscopic mastoidectomy. The mean length of skin incisions was 19.1 ± 4.5 mm, which was smaller than that in conventional mastoidectomy. In all cases, the average length of the major axis of the keyhole was <10 mm, indicating that sufficient minimally invasive surgery was achieved. The average depth from the keyhole to the deepest site was 21.6 ± 8.9 mm. There was no change in the mean hearing level before and after the surgery. CONCLUSION: PEES is a minimally invasive procedure for manipulating lesions in the mastoid. In addition, the combination of PEES and TEES is an ideal, minimally invasive procedure that can be used to treat all regions of the temporal bone.

Left ventricular systolic dyssynchrony index by three-dimensional echocardiography in patients with decreased left ventricular function: comparison with tissue Doppler echocardiography.

BACKGROUND: Three-dimensional echocardiography (3DE) can simultaneously assess left ventricular (LV) regional systolic motion and global LV mechanical dyssynchrony. METHODS: We used 3DE to measure systolic dyssynchrony index (SDI) (standard deviation of the time from cardiac cycle onset to minimum systolic volume in 17 LV segments) in 100 patients and analyzed the association of SDI with other parameters for LV systolic function or dyssynchrony. Eighteen patients who underwent cardiac resynchronization therapy (CRT) were also evaluated at 6 months after CRT, and the association of baseline SDI and tissue Doppler imaging (TDI) dyssynchrony index (Ts-SD) with the change of LV end-systolic volume (ESV) analyzed. Ts-SD was calculated using the standard deviation of the time from the QRS complex to peak systolic velocity. RESULTS: There was a significant inverse correlation between LVEF and SDI (r =-0.686, P < 0.0001). QRS duration was also significantly correlated to SDI (r = 0.407, P < 0.0001). There was a significant positive correlation between baseline SDI and the decrease in LVESV after CRT (r = 0.42). Baseline SDI was significantly greater in responders (10 patients) than in nonresponders (16.4 ± 5.1 vs. 7.9 ± 2.4%, P < 0.01), but there was no significant difference in Ts-SD. SDI > 11.9% predicted CRT response with a sensitivity of 90% and a specificity of 75%. CONCLUSIONS: SDI derived from 3DE is a useful parameter to assess global LV systolic dyssynchrony and predict responses to CRT.

Left atrial volume predicts adverse cardiac and cerebrovascular events in patients with hypertrophic cardiomyopathy.

AIMS: To prospectively evaluate the relationship between left atrial volume (LAV) and the risk of clinical events in patients with hypertrophic cardiomyopathy (HCM). METHODS: We enrolled a total of 141 HCM patients with sinus rhythm and normal pump function, and 102 patients (73 men; mean age, 61±13 years) who met inclusion criteria were followed for 30.8±10.0 months. The patients were divided into two groups with or without major adverse cardiac and cerebrovascular events (MACCE), a composite of stroke, sudden death, and congestive heart failure. Detailed clinical and echocardiographic data were obtained. RESULTS: MACCE occurred in 24 patients (18 strokes, 4 congestive heart failure and 2 sudden deaths). Maximum LAV, minimum LAV, and LAV index (LAVI) corrected for body surface area (BSA) were significantly greater in patients with MACCE than those without MACCE (maximum LAV: 64.3±25.0 vs. 51.9±16.0 ml, p=0.005; minimum LAV: 33.9±15.1 vs. 26.2±10.9 ml, p=0.008; LAVI: 40.1±15.4 vs. 31.5±8.7 ml/mm2, p=0.0009), while there were no differences in the other echocardiographic parameters.LAV/BSA of ≥40.4 ml/m2 to identify patients with cardiovascular complications with a sensitivity of 73% and a specificity of 88%. CONCLUSION: LAVI may be an effective marker for detecting the risk of MACCE in patients with HCM and normal pump function.

Intramuscular transplantation of G-CSF-mobilized CD34(+) cells in patients with critical limb ischemia: a phase I/IIa, multicenter, single-blinded, dose-escalation clinical trial.

A number of preclinical studies have indicated the therapeutic potential of endothelial progenitor cells for vascular regeneration in ischemic diseases. A phase I/IIa clinical trial of transplantation of autologous CD34(+) cells, the endothelial and hematopoietic progenitor-enriched fraction, was performed in no-option patients with atherosclerotic peripheral artery disease or Buerger's disease with critical limb ischemia (CLI). CD34(+) cells were isolated from the G-CSF-mobilized apheresis product using a magnetic cell sorting system. CD34(+) cells (10(5)/kg, n = 6; 5 x 10(5)/kg, n = 8; or 10(6)/kg, n = 3) were injected i.m. into the leg with more severe ischemia. The Efficacy Score, representing changes in the toe brachial pressure index (TBPI), Wong-Baker FACES pain rating scale, and total walking distance 12 weeks after cell transplantation, the primary endpoint, was positive, indicating improvement in limb ischemia in all patients, although no significant dose-response relationship was observed. During the 12-week observation after cell therapy, the Wong-Baker FACES pain rating scale, TBPI, transcutaneous partial oxygen pressure, total or pain-free walking distance, and ulcer size serially improved in all patients. No death or major amputation occurred, and severe adverse events were rare, although mild to moderate events relating to G-CSF and leukapheresis were frequent during the 12-week follow-up. In conclusion, the outcomes of this prospective clinical study indicate the safety and feasibility of CD34(+) cell therapy in patients with CLI. Favorable trends in efficacy parameters encourage a randomized and controlled trial in the future.

[Congenital ossicular malformation: a study of 27 ears].

Despite otological surgical progress improving clinical congenital ossicular malformation management, some cases remain inadequately treated. We report 27 cases of congenital ossicular malformation, focusing on reasons for remaining or delayed postoperative hearing loss evaluated in 27 congenital ossicular malformation cases in Kyoto Prefecture from 2002 to 2008. Overall success was 93% (25/27) 6 months postoperatively. Two ears had no hearing improvement and three delayed hearing loss 8 to 48 months postoperatively. The first two ears underwent small fenestration stapedotomy with malleus attachment piston, and the other three tympanoplasty type III using an autologous ossicle or total ossicular replacement prosthesis (TORP) as a columella. We discuss problems and solutions using a malleus attachment piston or prosthesis, preoperative audio-and radiological findings, and operative findings including facial nerve anomaly and congenital cholesteatoma.

Detection of severe stenosis and total occlusion in the left anterior descending coronary artery with transthoracic Doppler echocardiography in the emergency room.

BACKGROUND: The noninvasive measurement of coronary flow velocity in the left anterior descending artery (LAD) has recently been realized by using the transthoracic Doppler echocardiography (TTDE). A couple of investigations demonstrated that the diastolic-to-systolic peak velocity ratio (DSVR) by TTDE is a simple and noninvasive method for the detection of severe stenosis in the elective settings. However, the usefulness of DSVR by TTDE in the emergency settings has not been evaluated. OBJECTIVE: The purpose of this study was to assess the clinical feasibility to document the LAD flow by TTDE in emergency patients who complained of chest pain. METHODS: We studied 49 consecutive patients with acute coronary syndrome who were going to undergo emergency coronary angiography (CAG) for the anatomical diagnosis and the facilitated percutaneous coronary intervention (PCI). Prior to CAG, we recorded the LAD flow by TTDE and measured the diastolic peak velocity (DVp), systolic peak velocity (SVp), and their ratio, DSVR (DVp/SVp) of LAD flow. RESULTS: By CAG, the culprit lesions actually resided in the proximal LAD in 36 patients. Among the 36 patients, we detected the Doppler LAD flow in 29. Five out of 7 patients who were unable to detect the LAD flow revealed total occlusions by CAG. DSVR of the LAD is significantly lower in 17 patients who showed severe stenoses (>90%) than those in the rest of 12 patients who did not show such critical stenoses (1.44 +/- 0.16 vs 2.10 +/- 0.26, P < 0.0001). CONCLUSION: In the emergency settings, a noninvasive assessment of the LAD flow by TTDE accurately estimates the critical stenotic lesions of the LAD.

Reoperation for early failure of a freestyle bioprosthesis using a full root technique.

The case is reported of a 65-year-old male who required reoperation for early failure of a Freestyle stentless valve aortic root bioprosthesis implanted using the full root technique. The bioprosthesis had been implanted to treat annuloaortic ectasia associated with severe aortic regurgitation (AR). At 18 months postoperatively, a new diastolic murmur developed, though without complaint by the patient. Transthoracic echocardiography demonstrated severe AR with aneurysmal dilatation of the non-coronary porcine sinus of Valsalva. Pseudoaneurysm formation, associated with perforation of the non-coronary sinus of Valsalva of the bioprosthesis, was observed at surgery. On inspection, the pseudoaneurysm had pushed the commissures inward, and had created severe aortic valve regurgitation. No infection or calcification was detected on the Freestyle valve, and the aortic root was successfully reconstructed using a composite graft.

Left atrial volume: predictor of atrial fibrillation in patients with degenerative mitral regurgitation.

BACKGROUND AND AIM OF THE STUDY: In patients with mitral regurgitation (MR) due to degenerative mitral valve prolapse (MVP), preoperative atrial fibrillation (AF) has been identified as an independent predictor of survival after surgery for MR. Thus, the determinants of preoperative AF may have critical implications to evaluate the timing of mitral valve repair. The study aim was to investigate the role of left atrial (LA) volume in predicting preoperative AF in patients with severe MR due to degenerative MVP. METHODS: Sixty-six patients with severe degenerative MR (regurgitant volume > or =60 ml, regurgitant fraction > or =50%, effective regurgitant orifice area > or =0.4 cm(2)) in sinus rhythm (SR) at diagnosis and conservatively managed were eligible for the study. Complete two-dimensional (2-D) echocardiographic and Doppler measurements, including the measurement of maximum LA volume, were performed in all patients. RESULTS: During follow up under conservative management (18.1+/-4.8 months), eight patients (12%) experienced conversion to AF, and 58 remained in SR. The mean LA dimension was 4.0+/-0.5 cm in patients with SR, and 5.1+/-0.8 cm in those who developed AF (p <0.0001). The mean LA volume and LA volume index (indexed to body surface area) were 95 +/-23 ml and 60+/-14 ml/m(2) respectively in patients with SR, and 166+/-66 ml and 104+/-42 ml/m(2) respectively in those who developed AF (both p <0.0001). The optimal cut-off value for LA volume to predict AF conversion was 117.5 ml (sensitivity 88%, specificity 83%), and for LA volume index was 75 ml/m(2) (sensitivity 88%, specificity 88%). CONCLUSION: LA volume measurement should be considered in patients with degenerative severe MR diagnosed in SR. A LA volume index > or =75 ml/m(2) reflects the risk of subsequent AF, and patients should be closely monitored.

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 (> or =2+, n=15 versus < or =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.

Coronary flow velocity pattern immediately after percutaneous coronary intervention as a predictor of complications and in-hospital survival after acute myocardial infarction.

BACKGROUND: Recently, it was reported that the degree of microvascular injury and left ventricular functional recovery during the chronic period can be predicted after treatment of the infarct-related artery based on the coronary flow velocity (CFV) pattern assessed using a Doppler guidewire. The aim of this prospective study was to examine whether the CFV pattern may predict complications and in-hospital survival after acute myocardial infarction (AMI). METHODS AND RESULTS: The study population consisted of 169 consecutive patients with a first anterior AMI successfully treated with percutaneous coronary intervention (PCI). We examined the CFV pattern immediately after PCI using a Doppler guidewire. In accordance with previous findings, we defined severe microvascular injury as a diastolic deceleration time < or =600 ms and the presence of systolic flow reversal. Patients were divided into two groups: those without severe microvascular injury (n=118; group 1) and those with severe microvascular injury (n=51; group 2). All of the patients who had cardiac rupture were in group 2. Congestive heart failure (CHF) was observed more frequently in group 2 than in group 1 (53% versus 8%, P<0.001). The in-hospital cardiac mortality rate was significantly higher in group 2 than in group 1 (18% versus 0%, P<0.001). Nine patients in group 2 died, 5 patients because of CHF and 4 patients because of cardiac rupture. CONCLUSIONS: These findings suggest that the CFV pattern is an accurate predictor of the presence or absence of complications and of in-hospital survival after AMI.

Prognosis of retrograde dissection from the descending to the ascending aorta.

BACKGROUND: Natural history of aortic dissection (AD) with intimal tear in the descending or abdominal aorta and retrograde extension into the ascending aorta (retrograde AD) remains unknown. The purpose of this study was to elucidate medium-term prognosis of patients with retrograde AD. METHODS AND RESULTS: Study population consisted of 109 patients with acute type A AD. There were 27 patients (25%) with retrograde AD and 82 patients (75%) with intimal tear in the ascending aorta (antegrade AD). In antegrade AD patients, 60 patients underwent surgery and 22 patients were treated medically. In retrograde AD patients, 14 patients showed localized crescentic high attenuation area along the ascending aortic wall without enhancement in computed tomography. Transesophageal echocardiography revealed complete thrombosis of false lumen (FL) in the ascending aorta (retrograde thrombosed). The remaining 13 patients showed incomplete or no thrombosis (retrograde nonthrombosed). All retrograde nonthrombosed AD patients underwent surgery except for 1 patient with stroke, whereas all retrograde thrombosed AD patients were treated medically. In-hospital mortality rate of retrograde AD patients was significantly lower than that of antegrade AD patients (15% versus 38%, P=0.027). The survival rates in retrograde AD patients were all 85% at 1, 2, and 5 years, which were significantly higher than those of antegrade AD patients (63%, 62%, and 57%, respectively)(P=0.009). CONCLUSIONS: Patients with type A retrograde AD have better medium-term prognosis than patients with antegrade AD. Retrograde AD patients with thrombosed FL in the ascending aorta could be treated medically with timed surgical repair.

Long-term prognosis of patients with type B aortic intramural hematoma.

BACKGROUND: The long-term clinical course of patients with type B aortic intramural hematoma (IMH) and predictors for progression remains unknown. The difference of aortic pathology may have a different impact on clinical course compared with classic aortic dissection (AD). The purpose of this study was to investigate long-term clinical course and predictors of progression in patients with type B IMH. METHODS AND RESULTS: Clinical data were compared retrospectively between 53 patients with acute type B IMH (IMH group) and 57 patients with acute type B AD (AD group). All patients were treated initially with medical therapy. Two patients in IMH group and 14 patients in AD group underwent surgical repair because of aortic enlargement. The in-hospital mortality rate in IMH group was significantly lower than that in AD group (0% and 14%, P=0.006). Mean follow-up periods were 53+/-43 months, which revealed 3 and 5 late deaths, respectively. Eleven patients with IMH showed progression (development of aortic dissection or aortic enlargement) in follow-up imaging study. The actuarial survival rates in IMH group were 100%, 97%, and 97% at 1, 2, and 5 years, which were significantly higher than those in AD group (83%, 79%, and 79%) (P=0.009). Multivariate analysis identified age >70 years and new appearance of an ulcerlike projection as the strongest predictors of progression in patients with IMH. CONCLUSIONS: Patients with type B IMH have better long-term prognosis than patients with AD. Older age and appearance of an ulcerlike projection are predictive for progression in patients with type B IMH.

Long-term prognosis of patients with type a aortic intramural hematoma.

BACKGROUND: Recent studies have shown an favorable short-term prognosis of patients with type A acute aortic intramural hematoma (IMH). The difference of aortic pathology may have a different impact on clinical course compared with classic aortic dissection (AD). The purpose of this study was to elucidate clinical features and long-term prognosis of patients with type A IMH. METHODS AND RESULTS: Clinical data were compared retrospectively between 30 patients with acute type A IMH (IMH group) and 101 patients with acute type A AD (AD group) who were admitted to our institutions from 1988 to 1998. In AD group, 72 patients underwent surgical repair and 29 patients were treated medically. All patients in IMH group were treated initially with supportive medical therapy. Thirteen patients who demonstrated progression to AD or increase in size of hematoma underwent timed surgical repair except for 1 patient. The overall in-hospital mortality rate in IMH group was significantly lower than that in AD group (7% and 34%, P=0.004). Follow-up periods were 56+/-37 (IMH group) and 60+/-42 months (AD group), which revealed 1 and 6 late deaths, respectively. The actuarial survival rates in IMH group were all 90% at 1, 2, and 5 years, which were significantly higher than those in AD group (67%, 66%, and 62%, respectively; P=0.004). CONCLUSIONS: Patients with type A IMH have better long-term prognosis than patients with AD.

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.

BACKGROUND: Myocardial 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. AIM: To 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. METHODS: Thirty 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. RESULTS: Pts were divided into 2 groups according to the deceleration time of coronary artery flow pattern (Group A; 20 pts with deceleration time > or = 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). CONCLUSION: The preserved microvasculature detecting by myocardial contrast echocardiography and coronary flow velocity reserve is related to functional recovery after acute myocardial infarction.

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.

Rapid freehand scanning three-dimensional echocardiography: accurate measurement of left ventricular volumes and ejection fraction compared with quantitative gated scintigraphy.

This study was performed to assess clinical feasibility of rapid freehand scanning 3-dimensional echocardiography (3DE) for measuring left ventricular (LV) end-diastolic and -systolic volumes and ejection fraction using quantitative gated myocardial perfusion single photon emission computed tomography as the reference standard. We performed transthoracic 2-dimensional echocardiography and magnetic freehand 3DE using a harmonic imaging system in 15 patients. Data sets (3DE) were collected by slowly tilting the probe (fan-like scanning) in the apical position. The 3DE data were recorded in 10 to 20 seconds, and the analysis was performed within 2 minutes after transferring the raw digital ultrasound data from the scanner. For LV end-diastolic and -systolic volume measurements, there was a high correlation and good agreement (LV end-diastolic volume, r = 0.94, P <.0001, standard error of the estimates = 21.6 mL, bias = 6.7 mL; LV end-systolic volume, r = 0.96, P <.0001, standard error of the estimates = 14.8 mL, bias = 3.9 mL) between gated single photon emission computed tomography and 3DE. There was an overall underestimation of volumes with greater limits of agreement by 2-dimensional echocardiography. For LV ejection fraction, regression and agreement analysis also demonstrated high precision and accuracy (y = 0.82x + 5.1, r = 0.93, P <.001, standard error of the estimates = 7.6%, bias = 4.0%) by 3DE compared with 2-dimensional echocardiography. Rapid 3DE using a magnetic-field system provides precise and accurate measurements of LV volumes and ejection fraction in human beings