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Atrial cycle length during atrial fibrillation and flutter waves may be correlated with atrial refractoriness and organization. The nature of the frequency by spectral analysis may reflect a profile of atrial cycle length. In this study, we developed a novel body surface 2-dimensional spectral map during fibrillation using vector-projected 187 channel ECG (187ch VP-ECG).
The study consisted of 28 patients (24 with atrial fibrillation (AFIB) and 4 atrial flutter (AFL) with valvular heart disease). We performed spectral analysis by maximum entropy modeling (MEM) in 4 second nonaveraged 187ch electrical current waves by 187ch VP-ECG. Body surface spectral features were displayed according to the frequency and power magnitude components. We verified the accuracy of the spectral features by a 64ch magnetocardiography (MCG).
The average dominant frequency in AFL by 187ch VP-ECG was lower than those in AFIB (4.6 ± 0.9 Hz in AFL, 7.2 ± 0.9 Hz in AFIB, P < 0.01). Comparison of average dominant frequency between 187ch VP-ECG and 64 ch MCG demonstrated good agreement (y = 0.86x+0.84, r² = 0.89, P < 0.0001). Body surface 2-dimensional spectral features demonstrated homogenous spectrum patterns in AFL, and in-homogenous spectrum patterns in AFIB.
In conclusion, novel body surface spectral mapping using 187ch VP-ECG may represent a 2-dimensional spectral feature that may be related to atrial refractoriness and organization.

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The efficacy of heart failure (HF) management programs is compromised by the challenge of early identification of patients at imminent risk. Segmental multifrequency bioelectrical impedance analysis can generate an “edema index” (EI) as a surrogate for the body fluid status. In this study, we tested whether integration of EI-guided management improved the 6-month outcomes of HF patients under multidisciplinary care. In total, 159 patients with acute HF were randomized into control, case management (CM), and EI-guided CM (EI) groups (n = 53 in each group). In the EI group, a management algorithm was designed based on the measured EI. The analyzed endpoints included HF-related and all cause-related events during the 6-month follow-up period. In the 6 months, there were 11 (6.9%) deaths, 19 (11.9%) HF-related rehospitalizations, and 45 (28.3%) all-cause-related rehospitalizations. Compared to the control (26.4%) and CM groups (15.1%), the EI group had a lower rate of HF-related death and rehospitalization (3.8%, P = 0.004). Multivariate analysis revealed that EI-guided management was an independent predictor of a lower HF-related event rate (hazard ratio = 0.15, 95%CI = 0.03~0.66, P = 0.012). Patients with a higher pre-discharge EI were older, had lower blood albumin and hemoglobin levels, and had a higher functional class and incidences of diabetes mellitus and chronic kidney disease. An increase in the pre-discharge EI by 0.001 increased the HF-related event rate by 6% (P = 0.002). Use of EI-guided management lowered this risk (P = 0.03). In conclusion, an EI-based HF management program demonstrated an event-lowering effect superior to traditional nurse-led multidisciplinary care in 6 months after an acute HF episode.

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A stress-induced myocardial perfusion abnormality (MPS), in the absence of angiographically significant epicardial coronary artery disease, is considered a “false-positive” test result. We hypothesized that echocardiography would provide complementary prognostic and pathophysiologic data relevant to the management of patients with MPS and normal coronary angiograms.
Accordingly, left atrial volume index (LAVi) was assessed by echocardiography in 38 patients with false positive MPS as defined by normal coronary angiograms and 26 patients with true negative MPS from a total of 1,356 patients stressed from July 2006-May 2008. Pathologically abnormal elevation of LAVi (≥ 32 mL/m²) was observed in 16 of 19 women (84%) and 11 of 19 men (58%) in the false positive MPS (FPMPS) group while none of the patients in the true negative MPS (TNMPS) group had elevated LAVi. In the FPMPS group mean LAVi was significantly higher in women than men (40.64 ± 11.4 mL/m² versus 32.6 ± 10.5 mL/m², P = 0.01). The mean LAVi in the FPMPS group was significantly different from the TNMPS group (36.6 ± 11.6 versus 21 ± 7 mL/m², P = 0.000). A stepwise logistic regression determined BSA, LAV and LAVi as useful in predicting false positive and true negative MPS. All three were significant predictors (P < 0.01) and the area under the ROC curve was 0.91.
Our findings in this relatively small cohort suggest that patients with false positive MPS have a greater increased LAVi.

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Diabetic patients with coronary artery disease are often asymptomatic, making appropriate care of such patients difficult. The purpose of this study was to investigate the prevalence of coronary lesions in asymptomatic diabetic patients. Coronary computed tomography (CT) angiography was performed in 120 consecutive diabetic patients (90 of whom were men, mean age 65, mean HbA1c 7.2%). Images from patients whose coronary artery calcium scores (CAC scores) were less than 400 were subjected to stenosis and plaque analysis. Significant stenosis was defined as coronary artery stenosis > 70%. High-risk plaque was defined as plaque having both a CT density < 30 Hounsfield Units (HU) and showing positive remodeling. Significant stenoses were identified in 30.5% of the patients. High-risk plaques were identified in 17.1% of the patients. Less than half of the high-risk plaques were obstructive plaques. There was a statistically significant association between significant stenosis and high-risk plaque by chi-square test (P = 0.022). We found significant stenosis even in patients whose CAC score = 0 at a rate of 5.0%. Using univariate logistic-regression analysis, we found that coronary risk factors associated with significant stenosis and high-risk plaque were dyslipidemia (P = 0.033) and current smoking (P = 0.030), respectively. We report for the first time, the prevalence of high-risk plaques in the arteries of patients with asymptomatic diabetes, as assessed by coronary CT angiography.

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Since distinct cholesterol and triglyceride concentrations in major lipoproteins and their subclasses may be related to atherosclerosis, we investigated the relationship of cholesterol and triglyceride concentrations in lipoprotein subclasses and the severity of carotid intima-media thickness (IMT), a surrogate marker of subclinical atherosclerosis. We studied 116 apparently healthy Japanese men (53 ± 9 years) without a history of cardiovascular diseases who were not taking any medication. Carotid IMT was measured by means of high-resolution vascular ultrasound. Plasma cholesterol and triglyceride concentrations in major lipoproteins and their subclasses were determined by HPLC with gel permeation columns. By univariate analyses, carotid IMT was the most closely related to age (r = 0.528, P < 0.001), followed by smoking habit expressed as pack-year cigarette consumption (r = 0.409, P < 0.001). In addition to total cholesterol and LDL cholesterol, carotid IMT was significantly associated with cholesterol and triglyceride concentrations in several LDL and VLDL subclasses. Stepwise multiple linear regression analysis revealed that age (β = 0.436, P < 0.001), smoking (pack-years) (β = 0.225, P = 0.007), and large LDL cholesterol (β = 0.175, P = 0.023) were independent predictors of determining carotid IMT (adjusted R² = 0.347, P < 0.001). These results indicate that large LDL cholesterol is an important, independent determinant of carotid IMT in healthy men.

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The ‘evidence’ in evidence-based medicine (EBM) is often limited to knowledge obtained from randomized controlled clinical trials (RCT). Most RCTs, however, have strict enrollment criteria which make patient background characteristics and clinical histories significantly different from those encountered in actual practice. Thus it is important to accumulate and analyze data obtained in daily practice to gain insight into a larger clinical picture. Recent developments in information technology and its lowered cost have enabled us to record clinical activity in much greater detail at a lower cost. These factors prompted us to design and develop a coronary angiography and intervention reporting system (CAIRS) to collect data and analyze outcomes of coronary intervention. The resulting advanced CAIRS can record detailed data on coronary angiographic and interventional procedures.
To date, data on 10,025 cases of coronary angiography, of which 3,574 were interventional, have been collected over a 5.5 year period. There were 4,343 unique patients, 3,115 (71.7%) of which were male. The overall mean age was 67.0 ± 11.5. The mean age of males was 66.3 ± 11.4 and that of females was 69.0 ± 11.4. About one-third of the patients never underwent a PCI procedure at our institution. For patients that underwent at least one PCI procedure at our institution, the prescription rate of statin increased from 50.8% in 2005 to 80.3% in 2011, while those of nitrate and ticlopidine decreased from 36.7% and 90.8% in 2005 to 21.3% and 0.8% in 2011, respectively. We have also implemented the same system at another institution and compared the data on stent usage between the two institutions, which revealed vastly different stent usage profiles.
In conclusion, we have successfully developed and implemented an advanced coronary angiography and intervention reporting system which we call CAIRS. Implementing the same system at multiple institutions and analyzing data collected from several institutions will provide detailed and timely insight into the ‘real world’ of coronary angiography and interventional procedures and their outcome.

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Coronary microvascular hyperplasia is a cause of microvessel angina, although the underlying cellular mechanisms remain unclear. We examined how mononuclear cells expressing β-actin (β-MNCs), which were identified in coronary vessels, induce coronary microvascular hyperplasia.
The presence of β-MNCs in coronary hyperplastic arterial (HAM) and venous microvessels (HVM) was examined by endomyocardial biopsy in 25 patients with suspected microvessel angina. β-MNCs were identified in 14 HAMs obtained from 11 patients. Basic fibroblast growth factor and heparin sulfate were injected into the infarcted myocardium to induce HAM and HVM in 28 beagles, and then we examined the role of β-MNCs in the onset of HAM and HVM. The following changes were observed after infarction induction in beagles: (a) migration of β-MNCs from the existing microvessels into the interstitial space at 1-2 weeks; (b) those traversing the adventitia into the media, but not intima, of microvessels; (c) their transformation to smooth muscle cells (SMCs) and/or connective tissues (collagen and elastin fi-bers); (d) and medial hyperplasia without intimal hyperplasia. Medial hyperplasia was classified into SMC-proliferative and both SMC- and connective tissue-proliferative types. β-MNCs expressed CD₃₄ but did not express other major vessel-related cell markers.
β-MNCs are a vascular progenitor, and migrate out of the adventitia into media, and participate in the etiology of coronary microvascular medial hyperplasia.

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It was previously thought that arteriogenesis and venogenesis are induced not only by proliferation of vessel-resident smooth muscle cells (SMCs) and endothelial cells (ECs) but also by migration of their precursors. However, it is not well understood through what route(s) the precursors migrate into the existing vessels.
We examined through what route or routes circulating mononuclear cells expressing β-actin (β-MNCs), which we identified in canine coronary vessels, migrate into coronary vessel walls and cause arteriogenesis and venogenesis at 1, 2, 4 and 8 weeks after induction of myocardial infarction.
The following changes were observed: (1) The β-MNCs migrated via coronary microvessels to the interstitial space at one week; (2) β-MNCs traversed the adventitia into the media and settled in parallel with pre-existing smooth muscle cells (SMCs) in arterioles and arteries and lost β-actin and acquired α-smooth muscle actin (α-SMA) to become mature SMCs at 2-4 weeks; (3) at the same time, other β-MNCs migrated across the adventitia and media into the intima and settled in parallel with pre-existing endothelial cells (ECs) and lost β-actin, while acquiring CD₃₁, to become mature ECs, resulting in arteriogenesis; (4) Similarly, β-MNCs migrated into venular and venous walls and became SMCs or ECs, resulting in venogenesis.
β-MNCs in the interstitial space expressed CD₃₄ but not other major vascular cell markers.
β-MNCs, possibly a vascular progenitor, migrate not from the lumen but across the adventitia into the media or intima of coronary vessels and transit to SMCs or ECs, and participate in arteriogenesis and venogenesis in ischemic myocardium.

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ONO-1301MS is a compound that acts as a prostacyclin agonist with thromboxane A2 synthase inhibitory activity. We investigated the effect of ONO-1301MS on myocardial remodeling in murine cardiac allografts. The hearts of Balb/c mice were transplanted into C3H/He mice (a full allomismatch combination) to assess acute rejection or C57BL/6 hearts into B6.C-H2^‹bm12› KhEg (a class II mismatch combination) to examine chronic rejection. ONO-1301MS did not prolong full allomismatch cardiac graft survival. Severe myocardial fibrosis with high collagen concentration was observed in untreated class II mismatch allografts on day 60. However, significantly suppressed myocardial fibrosis with less collagen synthesis was observed in the ONO-1301MS-treated group compared to the control group. ONO-1301MS could be an effective strategy to suppress chronic myocardial remodeling in cardiac transplantation.

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Acute myocardial infarction is sometimes complicated in patients with coronary spastic angina. The mechanisms are known to be plaque rupture and thrombosis induced by spasm, and reduced coronary flow due to prolonged spasm. We describe the case of a 45-year-old woman with coronary spastic angina who had a complication of an acute myocardial infarction. A specimen obtained with thrombectomy was the disrupted coronary artery wall accompanied by massive intramural hemorrhage. The cause of the acute myocardial infarction was thought to be an embolism of the coronary arterial wall that was disrupted by spasm and intramural hemorrhage.

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While diuretic drugs are commonly used in patients with congestive heart failure, the efficacy of their long-term use still remains controversial. Recently, a new class of diuretics, vasopressin receptor 2 antagonists, has been launched, and tolvaptan is one such drug. We describe our initial experience with this novel agent. Tolvaptan is potentially useful for treatment of heart failure patients with fluid overload who are refractory to conventional diuretic therapies.

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Mitral and aortic valve regurgitation is commonly found in osteogenesis imperfecta (OI) patients, however, little is known about the myocardial involvement in this disorder. An 82-year-old man with OI developed heart failure and was admitted to our hospital. Echocardiogram revealed severe mitral regurgitation without left ventricular (LV) dilatation, but with LV wall thickening. Histological analysis exhibited interstitial fibrosis of the myocardium in addition to myxoid changes of the mitral leaflet. These findings suggest that OI patients may develop LV remodeling together with diastolic dysfunction.

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