[Surgical treatment of Marfan syndrome; late results and new strategy].

UNLABELLED: Rapid progress has been made in the treatment of Marfan syndrome. Today, the treatment is relatively established and the results have also improved. Even if surgery is performed, however, vascular lesions may recur late after operation and late prognosis is poor considering the age of patients. Issues such as whether a reoperation should be conducted or how the late results might be improved are subjects of debate. Based on an analysis of recent late data, we have performed operations according to the new treatment policy, and here report the results. A total of 203 consecutive operations were conducted in 141 patients with Marfan syndrome who underwent surgery for aortic aneurysm at our department between February 1973 and August 2001. The mean age of patients was 39 (11 years with a male/female ratio of 95:46. At the first operation, 72 patients were diagnosed with annuloaortic ectasia (AAE), 17 patients with AAE + chronic dissection (DeBakey I), 14 patients with AAE + chronic dissection (DeBakey II), 6 patients with AAE + acute dissection (Stanford A), 11 patients with AAE + dissection (DeBakey III), 9 patients with dissection (DeBakey III) only, 3 patients with AAE + abdominal aortic aneurysm only, and 2 patients with abdominal aortic aneurysm only. The cause of reoperation were a new lesion in 17 patients, dissection in 13 patients and a true aneurysm in 4 patients. In 36 patients, an increase in the remaining lesion occurred or a scheduled stage 2 operation was performed. Reoperation was performed following the Bentall operation in 7 patients, dehiscence of the anastomotic region of the coronary artery in 5 patients, aneurysm of the anastomotic region of the coronary artery in 1 patients, and infection of the artificial valve with aneurysm of the anastomotic region of the coronary artery in 1 patient. Hospital deaths were reported in 8 (6%) patients who underwent composite valve graft replacement (including simultaneous arch replacement) for AAE. Hospital deaths also occurred in 8 (13%) patients who underwent a replacement of the aortic arch, descending thoracic or thoracoabdominal aorta, with no cases of paraplegia reported. In all cases, the replacement was extensive. The observed 10-year survival rate was 70% with a freedom from reoperation of 64%. Although dissection did not reduce the observed survival rate, the 10-year freedom from reoperation was significantly decreased at 49% (p = 0.0007). CONCLUSIONS: (1) Surgery is indicated for AAE when the maximum diameter of the aneurysm prior to onset of dissection is 5 cm. In the case of aortic arch without dissection, the Bentall operation with simultaneous arch replacement should be aggressively performed in order to minimize the future risk of vascular events and to eliminate the need for extensive replacement in a reoperation, a procedure which is associated with a high level of risk. (2) Extensive replacement which is associated with poor results should be avoided where possible and, instead, scheduled staged surgery should be aggressively performed in the early stage when the maximum diameter of the aneurysm in the descending aorta is 5 cm or less. (3) By paying adequate attention to patient education, outpatient follow-up using detailed diagnostic imaging, drug therapy, periodic late surveillance, expedition of scheduled surgery, and to the basic approach as well as endeavoring to improve surgical results by the use of new methods of treatment, it is anticipated that further improvement will be observed in late results.

[Mitral valve stenosis due to primary cardiac granulocytic sarcoma relapsing 8 years after complete remission: a case report].

A 28-year-old man was admitted because of dyspnea on effort. His tricuspid valve had been affected by granulocytic sarcoma and manifested tricuspid valve stenosis 8 years previously. After chemotherapy and radiation therapy, the tumor had disappeared and the tricuspid valve stenosis was relieved. Echocardiography showed that the posterior leaflet of the mitral valve was affected by the tumor, and Doppler ultrasonography revealed mild mitral valve stenosis. Biopsy of the anterior chest wall detected granulocytic sarcoma. Chemotherapy was started. The tumor size was reduced and the mitral valve stenosis became slight. Primary cardiac granulocytic sarcoma is very rare and stenosis of the atrioventricular valve by relapse of this tumor after complete remission is extremely unusual.

Angiotensin II type 2 receptor mediates vascular smooth muscle cell apoptosis in cystic medial degeneration associated with Marfan's syndrome.

BACKGROUND: Cystic medial degeneration (CMD) is a histological abnormality that is common in the aortic diseases associated with Marfan's syndrome (MFS). Although little known about the mechanism underlying CMD, several recent reports have demonstrated that vascular smooth muscle cell (VSMC) apoptosis could play a substantial role in CMD. On the other hand, angiotensin II (Ang II) has been reported to play an important role in the regulation of VSMC growth and apoptosis via the Ang II type 1 receptor (AT1R) and type 2 receptor (AT2R). METHODS AND RESULTS: To elucidate the role of Ang II signaling via the Ang II receptors in CMD, we investigated AT1R and AT2R mRNA expression and tissue concentration of Ang II in MFS aortas (n=10) and control aortas (n=12). Furthermore, we examined the effects of an ACE inhibitor, an AT1R blocker, and an AT2R blocker on serum deprivation-induced VSMC apoptosis by organ culture system. AT1R expression was significantly decreased (P<0.01) and AT2R expression was significantly increased (P<0.001) in MFS aortas compared with control aortas, and tissue Ang II concentration was significantly higher in CMD than in the control condition (P<0.01). Both the ACE inhibitor and AT2R blocker significantly inhibited serum deprivation-induced VSMC apoptosis (P<0.05), although the AT1R blocker did not inhibit apoptosis in cultured aortic media from MFS patients. CONCLUSIONS: Accelerated ACE-dependent Ang II formation and signaling via upregulated AT2R play a pivotal role in VSMC apoptosis in CMD, and the ACE inhibitor could have clinical value in the prevention and treatment of CMD.

Total and partial cardiac sympathetic denervation after surgical repair of ascending aortic aneurysm.

UNLABELLED: Sympathetic cardiopulmonary nerves arise from the cervical sympathetic trunks and travel alongside the great arteries to innervate the ventricles. Because of the proximity of the nerve and artery, cardiac sympathetic denervation may occur in patients who have just undergone surgery for the repair of an ascending aortic aneurysm. METHODS: To evaluate the cardiac sympathetic activity in aortic aneurysm, we performed cardiac 123I-metaiodobenzylguanidine (MIBG) imaging on 12 patients (mean age +/- SD, 47 +/- 17 y) before and after the surgical repair of an aneurysm. Seven patients scheduled for coronary artery bypass grafting also underwent 123I-MIBG imaging as controls for open-chest surgery. Planar images were obtained at 15 min (early) and 4 h (delayed) after injection of 111 MBq 123I-MIBG, and the cardiac 123I-MIBG uptake was graded quantitatively and visually. The quantitative evaluation was based on the heart-to-mediastinum ratio (H/M), and visual evaluation was performed by assigning a score of 0-3 (0 = absent, 1 = severely reduced, 2 = reduced, and 3 = normal). Heart rate variability using 24-h Holter electrocardiography was analyzed before and after the operation to generate a time-domain index of heart rate variability as an index of autonomic balance. RESULTS: In patients with aortic aneurysms, both early and delayed H/Ms were significantly decreased after the operation (early H/M: 1.84 +/- 0.16 before vs. 1.40 +/- 0.16 after, P = 0.001; delayed H/M: 1.79 +/- 0.38 before vs. 1.27 +/- 0.18 after, P = 0.004). Visual analysis of 123I-MIBG accumulation in early images showed absence of 123I-MIBG accumulation in 3 of 12 patients, a score of 1 in 7 patients, and a score of 2 in 2 patients. In contrast, no significant difference between H/M before surgery and H/M after surgery was seen in patients who underwent coronary artery bypass grafting. The time-domain index of heart rate variability was significantly lower after the operation than before (135 +/- 40 after vs. 96 +/- 27 before, P < 0.05). CONCLUSION: Cardiac sympathetic nerves are totally or partially denervated after the surgical repair of ascending aortic aneurysm.

Diagnostic implications of elevated levels of smooth-muscle myosin heavy-chain protein in acute aortic dissection. The smooth muscle myosin heavy chain study.

BACKGROUND: A rapid 30-minute assay of circulating smooth-muscle myosin heavy-chain protein has been developed as a biochemical diagnostic tool for aortic dissection. OBJECTIVE: To determine the sensitivity and specificity of this assay. DESIGN: Cross-sectional study. SETTING: 8 major cardiovascular centers in Japan. PATIENTS: 95 patients with acute aortic dissection, 48 patients with acute myocardial infarction, and 131 healthy volunteers. MEASUREMENTS: Levels of circulating smooth-muscle myosin heavy-chain protein. RESULTS: Patients with acute aortic dissection who presented within 3 hours after onset had elevated levels of circulating smooth-muscle myosin heavy-chain protein. In these patients, the assay had a sensitivity of 90.9%, a specificity of 98% compared with healthy volunteers, and a specificity of 83% compared with patients who had acute myocardial infarction; the clinical decision limit was 2.5 microgram/L. All patients with proximal lesions had elevated levels of smooth-muscle myosin heavy-chain protein, and only patients with distal lesions had decreased levels (<2.5 microgram/L). CONCLUSIONS: Levels of smooth-muscle myosin heavy-chain protein can be used to diagnose aortic dissection soon after symptom onset. The assay had the greatest diagnostic value in patients with proximal lesions.

[Myocardial involvement in rheumatic diseases].

The rheumatic diseases share many features. Clinically, they are often systemic diseases affecting multiple organs. Pathologically, these diseases share in common a diffuse vasculitis with an inflammatory process. Involvement of myocardium is also pathologically a common finding in rheumatic diseases, especially systemic sclerosis and dermatopolymyositis. Although clinical symptoms are often silent, potentially life-threatening manifestations are well known. Non invasive techniques such as nuclear imaging and echocardiography are useful to detect occult cardiac lesions. Clinically overt cardiac involvement portends an unfavorable prognosis. Early detection of subclinical involvement of myocardium is essential to improve prognosis.

Active remodeling of the coronary arterial lesions in the late phase of Kawasaki disease: immunohistochemical study.

BACKGROUND: Remodeling of the coronary artery lesions in Kawasaki disease has been observed in longitudinal angiographic studies. However, mechanisms of such remodeling have not yet been elucidated. METHODS AND RESULTS: We examined formalin-fixed specimens of the coronary arteries immunohistochemically by using antibodies against vascular growth factors (GFs) and their receptors in 7 children with Kawasaki disease, 9 children with no coronary disease, and 3 adults with atherosclerosis. In the thickened intima at stenotic sites and at recanalized vessels with Kawasaki disease, extensive expression of vascular GFs, such as transforming GF-beta(1), platelet-derived GF-A, and basic fibroblast GF, was observed both within and surrounding smooth muscle cells. Vascular endothelial GF was observed within smooth muscle cells. Furthermore, all of these GFs were strongly expressed in the newly formed microvessels within the intima. In the thinned media, these GFs were focally and weakly expressed. In contrast, these GFs were expressed only in the media in the control children. In cases of adult atherosclerosis, GFs were expressed diffusely in the media but focally and weakly if at all in the intima. CONCLUSIONS: Active remodeling of the coronary artery lesions in Kawasaki disease continues in the form of luxuriant intimal proliferation and neoangiogenesis for several years after the onset of the disease. This process is distinct from adult-onset atherosclerosis.

Apoptotic cell death in arrhythmogenic right ventricular cardiomyopathy: a comparative study with idiopathic sustained ventricular tachycardia.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a specific heart muscle disease of unknown etiology characterized by fatty and fibrofatty replacement of the right ventricular myocardium. It often manifests life-threatened ventricular arrhythmias. Previous studies have hypothesized that myocyte apoptosis contributes to the myocyte cell loss and fatty change in ARVC and may be induced by recurrent ventricular tachycardia (VT). We examined whether these progressive pathological changes result from apoptotic cell death in both autopsied and biopsied right ventricular myocardium from 35 patients with ARVC by using in situ terminal deoxynucleotidyl transferase assay (TUNEL) and agarose gel electrophoresis. We also studied the biopsied myocardium from 30 patients with idiopathic sustained VT whose origin was the outflow tract of the right ventricle. TUNEL-positive cells indicating DNA fragments were observed in some cardiomyocytes and fibroblasts in ARVC, but the numbers of TUNEL-positive myocytes were very low in idiopathic VT. DNA laddering was confirmed in two autopsied cases in ARVC, but not in a non-cardiac case who died. These results suggest that at least some cardiomyocytes and fibroblasts are subjected to apoptosis in ARVC, leading to the loss of myocardium with characteristic pathological changes and subsequently progressive cardiomyopathy. Furthermore, the apoptotic process may not result from myocardial ischemia due to repetitive VT.

Ultrastructural features of the myocardium of children with dilated cardiomyopathy.

We analyzed the electron-microscopic features of endomyocardial biopsy from pediatric patients with dilated cardiomyopathy (DCM). The specimens examined were taken from the right ventricle of ten patients aged from 2 to 15 years (mean 9.7 years). Biopsy specimens from eight patients with congenital heart disease (tetralogy of Fallot), aged from 3 to 12 (mean 7.3 years), and ten adult patients with DCM, aged from 32 to 60 (mean 45 years), were also examined. Patients considered to have endocardial fibroelastosis, arrhythmogenic right ventricular cardiomyopathy, specific cardiomyopathy, or coronary heart disease were excluded from this study. Specimens from pediatric patients with DCM showed various degrees of ultrastructural abnormalities of myocytes, including myofibrillar fragmentation, mitochondrial abnormalities, and intracellular edema. The ultrastructurally determined contractility failure index based on the severity of myocardial degeneration at the electronmicroscopic level was 4.9 +/- 1.1. This value was significantly higher than that in patients with tetralogy of Fallot (0.9 +/- 0.6, P < 0.001) but was not significantly different from that in adult patients with DCM (6.1 +/- 2.6). The index of pediatric patients with DCM who died within 3 years was high (6.0 +/- 0.8). Basal lamina layering of a capillary (BLL) in the myocardium was revealed in 1 of the 10 (10%) pediatric patients with DCM and in 6 of the 10 (60%) adult patients with DCM (P < 0.05). No BLL was noted in the patients with tetralogy of Fallot. These findings may be related to the pathogenesis of DCM in children and adults.

Histopathologic aspects of endomyocardial biopsy in pediatric patients with idiopathic ventricular tachycardia.

PURPOSE: The present study aimed to investigate the clinicopathologic findings and histopathologic characteristics of endomyocardial biopsy in pediatric patients with idiopathic ventricular tachycardia. METHODS: Histopathological findings of endomyocardial biopsy from 17 patients aged 7-15 years with idiopathic ventricular tachycardia (VT) but no organic heart disease were examined. Patients considered to have cardiomyopathy of the dilated, hypertrophic or specific form or arrhythmogenic right ventricular cardiomyopathy were excluded from this study. RESULTS: Advanced histopathologic findings, including myocyte hypertrophy, degeneration, interstitial fibrosis and disarrangement of muscle bundles, were disclosed in three cases (17.6%). One of these cases exhibited sustained VT with left bundle branch block configuration and showed increased frequency of VT during exercise testing. The remaining two cases had non-sustained VT with multifocal origin and had syncope episodes. Another 14 cases showed mild or no significant findings in the biopsy. CONCLUSIONS: These results indicate that advanced histopathology in endomyocardial biopsy is occasionally disclosed in cases of idiopathic VT, especially those of exercise-related VT or multifocal VT, and that these patients may be considered as having heart muscle disease.

Comparison of parameters of 123I-MIBG scintigraphy for predicting prognosis in patients with dilated cardiomyopathy.

123I-metaiodobenzylguanidine (MIBG) scintigraphy has been used to predict prognosis of patients with dilated cardiomyopathy (DCM), although it is unknown which parameter of MIBG is the most useful clinically. We studied MIBG in 59 patients with DCM, and followed them up to evaluate the prognosis of DCM. Single photon emission tomography (SPET) and planar imaging were performed, both early (e) and 4 h (delayed, d) post-injection. 201Tl (TL) SPET and radionuclide-ventriculography were also investigated. The total defect score of early and delayed MIBG and 201 Tl (MIBGeDS, MIBGdDS, TLDS) was analysed visually for each SPET image. The heart to mediastinum ratio (H/M) for both the early and delayed MIBG planar images and myocardial washout rate at 4 h were analysed quantitatively. Sixteen patients died during follow-up. Cox Hazards univariate analysis selected washout rate (P < 0.0001), H/Me (P = 0.0012), H/Md (P = 0.0001) and left ventricular ejection fraction (P = 0.0004) as indices for the prediction of cardiac death. Multivariate analysis selected washout rate as the most powerful independent predictor of prognosis (P < 0.0001). Survival curves with a threshold value of 52% for washout rate were able to differentiate a negative outcome from survival (P < 0.0001). TLDS, MIBGeDS and MIBGdDS were not useful in the prediction of prognosis. The washout rate of MIBG is the most potent predictor of cardiac death and is considered clinically useful.

Programmed cell death in the myocardium of arrhythmogenic right ventricular cardiomyopathy in children and adults.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of the right ventricular myocardium. Recently, the myocardial loss in ARVC has been suggested to be related to apoptosis. However, it is still unknown whether this phenomenon is already established in the myocardium of pediatric cases with this disease. We examined the histopathologic characteristics of the ventricular myocardium in specimens obtained from 10 patients, including 3 children with ARVC, and investigated the occurrence of apoptosis in the myocardium by terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) assay and agarose-gel electrophoresis of DNA. Endomyocardial biopsy specimens from the 10 cases and a necropsy sample from one adult case with ARVC were examined. Histopathologic examination of biopsy specimens from the pediatric cases revealed extensive fibrosis. Typical fatty infiltration was demonstrated in one of the 3 pediatric cases. These findings were similar to those in adult cases; the histopathologic index based on the severity of myocardial damage, including myocyte degeneration and fibrosis, was not significantly different from that in adult cases. TUNEL assay revealed positive reactivity of the myocardial cells. The apoptotic index was 1.4 +/- 0.4% in children and 1.6 +/- 0.5% in adults (difference not statistically significant). Agarose-gel electrophoresis of a DNA extract of the myocardial tissue of the autopsy case revealed DNA fragmentation. Cases with idiopathic ventricular tachycardia and control cases with a cardiac transplant (with no rejection) had minimal histopathologic findings and negative reactivity in the TUNEL assay. These results indicate that myocardial damage is already established in cases diagnosed as ARVC in childhood, and suggest that the myocardial damage is closely related to apoptosis in children, as well as in adults, in this disease.

A noninvasive method of measuring wave intensity, a new hemodynamic index: application to the carotid artery in patients with mitral regurgitation before and after surgery.

Wave intensity (WI) is a new hemodynamic index, which is defined as (dP/dt)(dU/dt) at any site of the circulation, where dP/dt and dU/dt are the time derivatives of blood pressure and velocity, respectively. Arterial WI in normal subjects has two positive sharp peaks. The first peak occurs during early systole when a forward-traveling compression wave is generated by the left ventricle. The magnitude of this peak increases markedly with an increase in cardiac contractility. The second peak, which occurs towards the end of systole, is caused by generation of a forward-traveling expansion wave by the ability of the left ventricle to actively stop aortic blood flow. The interval between the R wave of the ECG and the first peak of WI (R-1st peak interval) and the interval between the first and second peaks (1st-2nd interval) are approximately equal to the preejection period and left ventricular ejection time, respectively. Using a combined Doppler and echo-tracking system, we obtained carotid arterial WI noninvasively. We examined the characteristics of WI in 11 patients with mitral regurgitation (MR) before and after surgery, and 24 normal volunteers. In the MR group before surgery, the second peak was decreased and the (1st-2nd interval)/(R-R interval) ratio was reduced, compared with the normal group (140 +/- 130 vs 750 +/- 290mmHg m/s3. P < 0.0083; 20.7% +/- 3.4% vs 26.7% +/- 2.8%, P < 0.083). There were no significant differences in the first peak between the normal group and the MR group before and after surgery. The second peak in the MR group was increased significantly (P < 0.016 vs before surgery) to 1,150 +/- 830mmHg m/s3 in the early period after surgery (stage I), and to 1,090 +/- 580mmHgm/s3 in the late period after surgery (stage II). These values did not differ significantly from that of the normal group. At stage I, the (R-1st peak interval)/ (R-R interval) ratio was increased from 13.4% +/- 2.7% to 20.6% +/- 5.6% (P < 0.016 vs before surgery). At stage II, this ratio decreased to 16.2% +/- 2.8% (P < 0.016 vs stage I). but was still significantly higher than that before surgery. The (1st-2nd interval)/(R-R interval) ratio increased significantly after surgery (P < 0.016 vs before surgery) to values (27.0% +/- 4.5% at stage I and 28.9% +/- 2.6% at stage II) which did not differ significantly from that of the normal group. The recovery of the second peak after surgery suggests that the left ventricle had recovered the ability to actively stop aortic blood flow. Wave intensity is useful for analyzing changes in the working condition of the heart.

[Cardiac sympathetic denervation after aortic surgery in a patient with thoracic dissecting aneurysm: a case report].

We experienced a case of a 60 year-old man with cardiac sympathetic denervation after aortic graft replacement of ascending aorta for a dissecting aneurysm (Debakey type II). Fourteen years after pheochromocytomectomy (paraganglioma), the patient developed a severe chest pain, and admitted to the hospital for the diagnosis of dissecting aneurysm. CT scan with contrast enhancement revealed thrombosed dissecting aneurysm in the region of ascending aorta to aortic arch. Graft replacement was undergone on the same day. 123I-MIBG imaging 20 days after the operation showed severely attenuated myocardial uptake (heart to mediastinum ratio 1.19), although the MIBG imaging before the operation showed normal myocardial uptake (heart to mediastinum ratio 1.55). Heart rate variability analysis in Holter ECG showed that the power of the low frequency (LF), that of the high frequency (HF) and L/H ratio were severely decreased. MIBG and heart rate variability analysis indicated that cardiac sympathetic and parasympathetic nerve were denervated. This is the first report of cardiac sympathetic denervation after aortic vascular surgery. Clinical significance of cardiac sympathetic denervation after aortic vascular surgery is uncertain, and further investigation will be required.

Primary cardiac angiosarcoma of the right atrium undiagnosed by transvenous endocardial tumor biopsy.

A 50-year-old man was admitted with acute pericarditis. Echocardiography demonstrated a large mass on the right atrial free wall along with a pericardial effusion. We performed transvenous biopsy of this mass under transesophageal echocardiographic guidance. Though the biotome obtained the mass, the pathological findings were of organized thrombus. Two weeks later, a new precordial mass appeared around the left third rib and was suspected to be a metastasis. Incisional biopsy of this mass gave the diagnosis of angiosarcoma.

[Postoperative therapy using human atrial natriuretic peptide in cases of valve replacement].

The effect of hANP (atrial natriuretic peptide) was investigated clinically in 40 patients who underwent isolated valve replacement. Patients were divided into four groups: aortic regurgitation (AR), aortic stenosis (AS), mitral regurgitation (MR) and mitral stenosis (MS). Each group was divided into two subgroups: one was administered hANP after the operation until leaving ICU, and the other was not administered hANP. We measured the levels of hANP and c-GMP and blood pressure, pulmonary artery pressure, central venous pressure and levels of Na, K of urine and blood prcoperatively, immediately postoperatively and 1, 2, 4, 6 hours after operation. First, to examine the relationship between preoperative level of hANP and cardiac function, the relationship between preoperative level of hANP and history of cardiac failure and pulmonary artery wedge pressure (PAWP) were evaluated. Also, we evaluated the relationship between preoperative level of hANP and each dimension on echocardiography. There was a weak statistical relationship between hANP and PAWP (row = 0.39 (p = 0.04) Pearson correlation method) and there was no statistical relationship between hANP and duration of cardiac failure (row = 0.00445 (p = 0.98) Pearson correlation method). Preoperatively Left atrial diameter (LAD) showed a statistical relationship with level of hANP in every group using Spearman correlation method. Other dimensions such as left ventricular diastolic diameter (LVDd) and left ventricular systolic diameter (LVDs) and also fractional shortening (FS) did not show a strong correlation with preoperative level of hANP. Especially, in AS group there was a strong relationship between every dimension and preoperative level of hANP. Only in MS group LAD and the level of hANP were negatively related. This finding suggests that atrial dilatation results in reduction of secretion of hANP in cases of MS on long term follow up. Finally, hNAP therapy was shown to have a continuous diuretic effect, with stable hemodynamics.

Heart valve operation in acromegaly.

BACKGROUND: Intractable congestive heart failure is known as a serious complication of acromegaly, but valvular heart disease rarely occurs in acromegalic patients. We experienced 5 surgical cases of valvular heart disease associated with acromegaly. We describe the features of those cases in this report. METHODS: The patient characteristics and operative and pathologic findings were retrospectively studied. RESULTS: There were 4 men and 1 women. Age at operation was 59 +/- 5.5 years. Cardiac lesions consisted of 1 case of aortic regurgitation associated with mitral regurgitation, 1 of aortic regurgitation, and 3 of mitral regurgitation. Operative procedures consisted of 1 double valve replacement (aortic and mitral valve replacement), 1 aortic valve replacement, and 3 mitral valve replacements. The causes of aortic valvular regurgitation were aortic valvular degeneration and aortic annular dilatation. The causes of mitral regurgitation were chordal rupture and mitral valvular degeneration. Histopathologic examination of the excised valves showed mucopolysaccharide deposits and myxomatous degeneration of the leaflets. The myocardium showed fibrosis of interstitial spaces and endocardium, and disarrangement of muscle fibers. CONCLUSIONS: We report 5 successful surgical cases of valvular heart disease associated with acromegaly. Earlier operation is recommended for such cases because of acromegalic cardiomyopathy.

Redifferentiation of smooth muscle cells after coronary angioplasty determined via myosin heavy chain expression.

BACKGROUND: The pathophysiology of phenotypic modulation of smooth muscle cells (SMCs) involved in restenosis after angioplasty is not well understood. Smooth muscle myosin heavy chain (SM MHC) isoforms (SM1 and SM2) are specific markers for SMC differentiation. In particular, SM2 is useful as a marker of mature SMCs. SMemb is a nonmuscle myosin heavy chain (NM MHC) whose expression is upregulated in immature or activated SMC. METHODS AND RESULTS: To determine SMC phenotypes in neointimal tissues after percutaneous transluminal coronary angioplasty (PTCA), we performed immunohistochemistry on human coronary arteries with antibodies against alpha-SM actin, SM1, SM2, and SMemb. Tissues were obtained from six autopsied patients and from atherectomy specimens from 16 patients who had undergone PTCA. Medial SMCs were positive for alpha-actin, SM1, and SM2. Expression of SM1 and SM2 in the neointima varied with the time after intervention, whereas alpha-actin was constitutively expressed in all cases studied. Neointimal cells at 16 and 20 days after PTCA contained alpha-actin but little or no SM1 or SM2, indicating that these cells modulated their phenotype to the immature state. Neointimal SMCs recovered SM MHC expression, first SM1 and then SM2, by 6 months after PTCA. Increased expression of SMemb was found in the neointima but without apparent relationship to the time after PTCA. CONCLUSIONS: Neointimal SMCs show features of an undifferentiated state, indicated by altered expression of SM MHC, and undergo redifferentiation in a time-dependent manner. The expression of SM MHC isoforms provides insight into the biology of healing after angioplasty and furnishes useful tools for the understanding of the roles of differentiation and phenotypic modulation of SMCs in human vascular lesions.

Serum levels of vascular endothelial growth factor in patients with acute myocardial infarction undergoing reperfusion therapy.

1. Vascular endothelial growth factor, a potent angiogenic mitogen, is known to be induced in response to ischaemia as well as being secreted from tumour cells. However, the precise mechanism of vascular endothelial growth factor release in acute myocardial infarction and the effects of coronary reperfusion on the circulating levels of vascular endothelial growth factor are still unknown. 2. Nineteen patients with acute myocardial infarction who underwent early reperfusion therapy were studied. Serum levels of vascular endothelial growth factor before reperfusion were markedly increased as compared with those in 19 healthy control subjects [252.4 +/- 158.1 pg/ml (mean +/- SD) compared with undetectable]. After reperfusion, the serum vascular endothelial growth factor levels rapidly returned almost completely to the normal control range. 4. These data strongly suggest that the serum level of vascular endothelial growth factor is one of the most sensitive indicators of myocardial ischaemia.