Predicting the clinical course in hypertrophic cardiomyopathy using thallium-201 myocardial scintigraphy.

AIMS: This study aimed to evaluate the changes in left ventricular remodelling with time in patients with hypertrophic cardiomyopathy (HCM) using thallium-201 myocardial scintigraphy. METHODS AND RESULTS: Forty-eight patients with HCM participated in the study. The extent score (ES) and a newly devised index termed the 'mean count change' (MCC) were used to evaluate the myocardial perfusion defects. Using the amount of thallium-201 uptake (TU), MCC (%) was calculated using the following formula: (last TU - initial TU)∕initial TU × 100. To confirm the site of the lesion, the left ventricle was divided into five segments: anterior, septal, inferior, lateral, and apex. Cardiovascular complications and deaths were recorded. The mean follow-up period was 8.6 ± 2.0 years. ES increased from 17.4 ± 13.7% to 44.0 ± 22.3% (P < 0.0001). MCC increased from 0% to 12.0 ± 9.0% (P < 0.0001). The apex was the most frequent site of lesion. Twenty-seven patients (56.3%) had experienced left ventricular heart failure (LVHF). Both ES and MCC were greater in patients with LVHF than in those without LVHF. An overlap between the two groups was greater in ES than in MCC. Patients with LVHF had a higher incidence of atrial fibrillation and apoplexy. Nineteen patients (39.6%) died during the study period; 14 died from LVHF, 3 from sudden cardiac death, and 2 from cancer. CONCLUSIONS: Thallium-201 myocardial scintigraphy is useful for detecting the severity of myocardial damage and for confirming the lesion site in patients with HCM. MCC may be superior to ES in the evaluation of these changes with time.

Impact of chronic kidney disease on the diuretic response of tolvaptan in acute decompensated heart failure.

AIM: This study investigated the relationship between the initial diuretic response to tolvaptan and clinical predictors for tolvaptan responders in patients with acute decompensated heart failure (ADHF). METHODS AND RESULTS: Patients (153) with ADHF (clinical scenario 2 or 3 with signs of fluid retention) who were administered tolvaptan were enrolled. Tolvaptan (15 or 7.5 mg) was administered for at least 7 days to those patients in whom fluid retention was observed even after standard treatment. The maximum urine volume immediately after tolvaptan administration showed good correlations with the ejection fraction and estimated glomerular filtration rate that were independent predictors of the urine volume (UV) responders (≥1500 mL increase in urine volume). The diuretic response (in terms of maximum diuresis) diminished with advancing chronic kidney disease (CKD) stage and concomitant deterioration of the renal function. Furthermore, advanced CKD was a significant negative predictor for the body weight (BW) responders (2.0% decrease in the body weight within 1 week after starting tolvaptan). As compared with non-CKD, the presence of advanced CKD predicts poor diuretic response for both UV and BW responders. CONCLUSIONS: The diuretic response following tolvaptan administration gradually diminished with progressive deterioration of the CKD stage. Worsening renal function was not observed. Tolvaptan is effective in treating CS2 or CS3 ADHF patients who present fluid retention and congestion, suggesting its potential efficacy for fluid management in the ADHF patients with CKD without worsening the renal function.

Correlation between plaque vulnerability of aorta and coronary artery: an evaluation of plaque activity by direct visualization with angioscopy.

This study investigated the relationship between the degree of atherosclerotic changes in the descending thoracic aorta (TA) and the coronary artery using angioscopy. Twenty-five consecutive patients undergoing angioscopy of the TA and coronary angiography were enrolled in this study. Participants were divided into three groups according to the angioscopic grading of the TA: white plaque group (W-group), yellow plaque group (Y-group) and intensive yellow, ruptured plaque with ulceration and/or thrombus group (RP-group). The maximum plaque grade, plaque score, number of yellow plaques, frequency of yellow-plaque grades by coronary angioscopy, and SYNTAX score by coronary angiography were evaluated. Brachial-artery pulse wave velocity and high-sensitivity C-reactive protein level tended to be higher in the RP-group than in the other groups, although the differences were not statistically significant. The SYNTAX score was significantly higher in the RP-group than in the W-group (W-group 4.0 ± 3.6 vs. RP-group 17.5 ± 10.0, P = 0.045). In addition, the angioscopic maximum plaque grade, plaque score, and number of yellow plaques in the RP-group were significantly higher than in the W-group (maximum plaque grade W-group 0.8 ± 0.4 vs. RP-group 1.8 ± 0.8, P = 0.026; plaque score W-group 1.0 ± 1.2 vs. RP-group 4.0 ± 1.4, P = 0.014; and number of yellow plaques W-group 1.0 ± 1.2 vs. RP-group 2.5 ± 0.5, P = 0.023). The yellow-plaque grade in the coronary artery was correlated significantly with the plaque grading of TA (P = 0.043). Our study suggests that the angioscopic progression of aortic atherosclerosis is closely associated with vulnerability to and the extent of coronary stenosis, indicating that vulnerability toward atherosclerotic plaque development occurs simultaneously in the coronary tree and systemic arteries.

An autopsy case of acute cor pulmonale and paradoxical systemic embolism due to tumour cell microemboli in a patient with breast cancer.

A 62-year-old woman was admitted to our hospital because of severe respiratory distress. Diagnostic imaging studies suggested the existence of inexplicable cor pulmonale. Although we immediately sought the aetiology of her severe condition, she died suddenly on the fourth day after admission. Postmortem autopsy revealed tumour cell microemboli in the small pulmonary arteries. In addition, tumour cell embolisation identical to that in primary breast cancer cells was also observed in microvessels in systemic multiple organs, such as the liver, brain, kidneys, spleen, uterus, bone marrow and adrenal glands-with simultaneous findings of peripheral infarction. Systemic tumour cell embolism mediated through the patent foramen ovale superimposed on pulmonary tumour cell emboli (PTCE) is considered to be the mechanism underlying inexplicable cor pulmonale. The rapid aggravation of her condition terminated in death.

Relationship between plaque composition and no-reflow phenomenon following primary angioplasty in patients with ST-segment elevation myocardial infarction--analysis with virtual histology intravascular ultrasound.

BACKGROUND: The angiographic no-reflow phenomenon after primary percutaneous coronary intervention (PCI) carries a poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI). However, the type of plaque composition that associates with the angiographic no-reflow phenomenon remains unclear. METHODS: A total of 44 patients with STEMI were enrolled in this study. After thrombectomy with an aspiration catheter, virtual histology intravascular ultrasound (VH-IVUS) of the infarct-related vessel was performed. Patients were divided into two groups according to final thrombolysis in myocardial infarction (TIMI) flow grade at the completion of PCI procedure. Complete reperfusion group (CR-group) was defined as final TIMI flow grade 3, and no-reflow group (NR-group) was defined as final TIMI flow < or = 2. The relationship between plaque composition and angiographic no-reflow phenomenon was analyzed. RESULTS: The angiographic no-reflow phenomenon was observed in 20 individuals. The summation of the percentage of fibrofatty+necrotic core and fibrofatty+dense calcium was significantly higher in the NR-group. Receiver-operating characteristics analysis revealed that the summation of the volume and percentage of fibrofatty+necrotic core (> 20.1 mm(3), 26.2%) and fibrofatty+dense calcium (> 20.0 mm(3), 22.6%) predict the angiographic no-flow phenomenon. CONCLUSION: The fibrofatty-rich component with necrotic core or dense calcium derived from VH-IVUS is closely related to the angiographic no-reflow phenomenon observed in primary PCI.

Endothelial nitric oxide synthase gene polymorphism (Glu298Asp) in patients with coexistent hypertrophic cardiomyopathy and coronary spastic angina.

Coronary vasospasm appears to play a significant role in the etiology of myocardial ischemia in patients with hypertrophic cardiomyopathy (HCM). Furthermore, the management of patients with coexistent HCM and coronary spastic angina (CSA) presents a therapeutic challenge. The purpose of this study was to examine the Glu298Asp variant of the endothelial nitric oxide synthase (eNOS) gene to determine whether this polymorphism was associated with susceptibility to CSA in patients with HCM. The eNOS gene polymorphism (Glu298Asp) was genotyped in 150 HCM patients by the TaqMan chemical method. Patients were classified into group A (n=12) if they had CSA provoked by intracoronary acetylcholine, and group B (n=138) if they did not. In group A, the frequency of Glu/Glu, Glu/Asp, and Asp/Asp genotypes was 5 (41.7%), 6 (50%), and 1 (8.3%), respectively. In group B, it was 119 (86.2%), 17 (12.3%), and 2 (1.5%), respectively. The frequency of the Asp298 variant was significantly higher in group A than in group B (P<0.001). Multivariate logistic regression analysis showed that the Asp298 variant was a significant risk factor for CSA (odds ratio 11.8; P<0.001) that was independent of age, gender, smoking status or body mass index. Significantly more drugs were used by the patients in group A than those in group B and the patients with the Asp298 variant were treated with significantly more drugs than those without it. In conclusion, the Asp298 variant of the eNOS gene may be associated with CSA in HCM patients. HCM patients with CSA or the Asp298 variant may need more drugs to relieve their symptoms.

Relation of circulating interleukin-6 to left ventricular remodeling in patients with reperfused anterior myocardial infarction.

BACKGROUND: During the remodeling process after myocardial infarction (MI), the expression of proinflammatory cytokines is enhanced in the myocardium. However, only a few clinical studies have been conducted on cytokine involvement in left ventricular (LV) remodeling after MI. HYPOTHESIS: Circulating proinflammatory cytokines may be involved in LV remodeling in patients with reperfused MI. METHODS: We studied 25 patients with acute anterior MI who had undergone coronary reperfusion therapy, and 10 normal control subjects with no cardiac disease. In all patients, LV ejection fraction, end-diastolic volume index (EDVI), and end-systolic volume index (ESVI) were determined using left ventriculography at the acute phase and 6 months after onset. The delta EDVI and delta ESVI were calculated as the value of LV volume reduction, suggesting LV reverse remodeling. Serum levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha were measured using enzyme-linked immunosorbent assay. RESULTS: Serum levels of IL-6 and TNF-alpha at the acute phase were significantly higher in patients with MI than in control subjects (both p < 0.05). The IL-6 levels correlated well negatively with delta EDVI (r = 0.779, p = 0.039), whereas no correlation was found for TNF-alpha. According to multivariate analysis, IL-6 at the acute phase was a significant independent predictor for LV remodeling after reperfused MI (p = 0.007). CONCLUSIONS: Circulating IL-6 levels correlated closely with LV geometric changes during the remodeling process in patients with reperfused MI. Our study addresses the usefulness of another marker for LV remodeling after MI.

[Cardiac tamponade with paroxysmal atrial flutter controlled by antituberculous therapy].

We report a rare and unique case of possible extrapulmonary tuberculosis in an 83-year-old man who had cardiac tamponade and paroxysmal atrial flutter. The patient was admitted to our hospital because of syncope. The cardiac tamponade and paroxysmal atrial flutter were treated by pericardiocentesis and drainage of bloody pericardial fluid. Mycobacterium tuberculosis was not detected in diagnostic specimens, nor was any evidence of malignancy found. The remarkable elevation of adenosine deaminase and the predominance of lymphocytes in the pericardial fluid, considering the past history of tuberculosis, led to a diagnosis of extrapulmonary tuberculosis. After receiving standard antituberculous therapy by ethambutol, isoniazid, and rifampicin, the patient recovered and has remained well up to the present day. Thirty-six months have passed since his recovery without the recurrence of cardiac tamponade or any other cardiac events.

Rapid progression of primary cardiac leiomyosarcoma with obstruction of the left ventricular outflow tract and mitral stenosis.

We report a 73-year-old woman with primary cardiac leiomyosarcoma in the left atrium and ventricle. The tumor progressed very rapidly for 2 months after initial clinical evaluation. Obstruction of the left ventricular outflow tract and mitral stenosis were induced by the tumor. Urgent surgical resection was performed because she had cardiogenic shock due to paroxysmal atrial fibrillation. We could not resect the tumor completely because of severe invasion. She refused postoperative chemotherapy and radiotherapy, and died suddenly at home 89 days after surgery. To our knowledge, this is the first observation of mitral stenosis concomitant with obstruction of the left ventricular outflow tract in a patient with primary cardiac leiomyosarcoma.

Effect of beta-blockers on insulin resistance in patients with dilated cardiomyopathy.

The aim of this study was to evaluate the effect of beta-blockers on insulin resistance in patients with dilated cardiomyopathy (DCM). A secondary aim was to determine the effect of this treatment on plasma concentrations of tumor necrosis factor-alpha (TNF-alpha) and to investigate the relationships between this adipocytokine and insulin resistance. Insulin resistance determined using the Homeostatic Model Assessment (HOMA), echocardiographic measurements and analysis of plasma TNF-alpha concentration were carried out in 47 patients with DCM without diabetes mellitus before and after 6 months of beta-blocker therapy. A reduction in left ventricular dimensions and an associated increase in ejection fraction occurred with beta-blocker. The treatment resulted in a significant decrease in insulin resistance (HOMA index: Baseline, 2.73+/-3.36 vs, Month 6, 1.58+/-1.33, p=0.0347). Beta-blockade was also associated with a decrease in plasma TNF-alpha concentration although no significant relationship between this change and the improvement in insulin resistance was observed. Beta-blocker therapy in patients with DCM improved not only cardiac function, but also insulin resistance. The mechanism of the change in insulin function remains unclear, but may be related to improvements in left ventricular function or an attenuation of the inhibitory effect of reduction in TNF-alpha on insulin signaling.

Role of angiotensin II-regulated apoptosis through distinct AT1 and AT2 receptors in neointimal formation.

BACKGROUND: In vitro studies suggest that angiotensin II type 1 and type 2 (AT1 and AT2) receptors exert opposite effects in terms of vasoconstriction, natriuresis, and cell growth, but the role of these receptors in cardiovascular remodeling in vivo is still an enigma. In this study, we tested the hypothesis that AT2 exerts an antiproliferative effect by inducing apoptosis, thereby antagonizing AT1a in vascular remodeling. METHODS AND RESULTS: Vascular injury was induced by polyethylene cuff placement around the left femoral artery of AT1a-null (AT1aKO), AT2-null (AT2KO), and wild-type mice. Neointimal formation as well as DNA synthesis in vascular smooth muscle cells (VSMC) after vascular injury was exaggerated in AT2KO mice, but they were both suppressed in AT1aKO mice compared with those in wild-type mice. In contrast, the number of apoptotic cells in the injured artery in VSMC was significantly increased in AT1aKO mice but decreased in AT2KO mice. Reverse transcriptase-polymerase chain reaction analysis revealed that the expression of bax mRNA was attenuated in AT2KO mice. On the other hand, the expression of bcl-2 and bcl-x(L) mRNA was enhanced in AT2KO mice but attenuated in AT1aKO mice. Immunohistochemical staining with antibody to the bcl-2 protein family supported these results. CONCLUSIONS: Our results suggest that AT2 exerts antiproliferative effects and proapoptotic changes in VSMC by counteracting AT1a in the process of neointimal formation after vascular injury.

Relationship between cardiomyocyte cell death and cardiac function during hypertensive cardiac remodelling in Dahl rats.

The exact mechanisms responsible for the progression of heart failure remain unclear. We investigated the in vivo relationship between the incidence of apoptotic cell death and left ventricular function serially from the beginning of hypertension to decompensated heart failure in Dahl salt-sensitive rats. Dahl salt-resistant and Dahl salt-sensitive rats were fed on a high-salt diet from 6 weeks of age. Systolic blood pressure was recorded by the tail-cuff method every week. Cardiac function in vivo was evaluated by echocardiography and cardiac catheterization. Cardiomyocyte apoptosis was detected by the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) method. The gene expression of Bax, Bcl-2 and Bcl-xL was analysed by Northern blotting. The TUNEL method revealed that the incidence of cardiomyocyte apoptosis was significantly increased in the hearts of 18-week-old Dahl salt-sensitive rats (apoptotic index 1.3 +/- 0.1%). Northern blot analysis revealed that the Bcl-xL mRNA level increased gradually during the progression towards heart failure. In conclusion, these data suggest that cardiomyocyte apoptosis is a terminal event, and plays a role as an aggravating factor in the vicious cycle of heart failure.