Left ventricular (LV) remodeling following myocardial infarction (MI) is the result of complex interactions between various factors, including presence or absence of early revascularization. The impact of early revascularization on the relationship between infarct tissue characteristics and LV remodeling is incompletely known. Therefore, we investigated in patients with versus without successful early revascularization for acute MI potential relations between infarct tissue characteristics and LV remodeling with contrast-enhanced (CE) cardiovascular magnetic resonance (CMR). Patients with versus without successful early revascularization underwent CE-CMR for tissue characterization and assessment of LV remodeling including end-diastolic and end-systolic volumes, LV ejection fraction, and wall motion score index (WMSI). CE-CMR images were analyzed for infarct tissue characteristics including core-, peri- and total-infarct size, transmural extent, and regional scar scores. In early revascularized patients (n = 46), a larger area of infarct tissue correlated significantly with larger LV dimensions and a more reduced LV function (r = 0.39-0.68; all P ≤ 0.01). Multivariate analyses identified peri-infarct size as the best predictor of LV remodeling parameters (R² = 0.44-0.62). In patients without successful early revascularization (n = 47), there was no correlation between infarct area and remodeling parameters; only peri-infarct size versus WMSI (r = 0.33; P = 0.03) and transmural extent versus LVEF (r = -0.27; P = 0.07) tended to be related. A correlation between infarct tissue characteristics and LV remodeling was found only in patients with early successful revascularization. Peri-infarct size was found to be the best determinant of LV remodeling. Our findings stress the importance of taking into account infarct tissue characteristics and success of revascularization when LV remodeling is studied.

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Large infarcts are associated with a terminal QRS-distortion in ST-elevation myocardial infarction (STEMI) patients. Late gadolinium enhancement (LGE) on the cardiac MRI (CMR) can depict an infarct distribution. However, less is known about the relationship between the LGE findings and QRS-distortion on admission, including the best ECG-lead location to reveal the QRS-distortion (DIS-lead) in STEMI patients. Fifty STEMI patients successfully treated with percutaneous coronary intervention were classified into two groups according to whether the QRS-distortion was positive (+) or negative (−). The LGE on a recent CMR was classified into 12 left ventricular segments (Basal-Middle-Apical × Anterior-Septal-Inferior-Lateral). The coincidences between the segmental LGE scores and DIS-lead were investigated. All patients were divided into 23 QRS-distortion (+) and 27 QRS-distortion (−) groups. The total LGE score was significantly greater in the QRS-distortion (+) group (14.7 ± 6.8 versus 9.6 ± 6.2, P < 0.01). The highest LGE score in 96% of QRS-distortion (+) patients was 4, and a score 4 segment indicated a good selection of the DIS-lead (86.4%). QRS-distortion in the ECG on admission represents severe transmural infarction in the LGE using CMR, which represents large infarcts in STEMI patients.

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Although the clinical benefits of implantable cardioverter-defibrillators (ICDs) have been demonstrated, inappropriate therapies (IATs) cannot be completely avoided even with the most advanced devices. Recently, IATs are considered to decrease the ventricular function and prognosis of a patient. The aim of this study was to investigate the predictors of IAT with parameters during cardiopulmonary exercise stress test (CPX). Sixty consecutive ICD patients underwent symptom-limited CPX, and were divided into IAT (+) and IAT (−) groups. During and after CPX, ECG and hemodynamic parameters of systemic blood pressure, heart rate, and maximal O₂ consumption (max VO₂) were evaluated every minute. In selected patients, sympathetic and parasympathetic activities were evaluated with analyses of heart rate variability (HRV). No significant differences were observed in clinical background parameters. In the CPX parameters, only the maximal heart rate exhibited a significant difference between the IAT (+) group and the IAT (−) group (154.8 ± 5.9 versus 137.9 ± 4.2 beats per minute, P = 0.032), and LF/HF was higher during the recovery phase 4 minutes after peak exercise in the former group (4.5 ± 1.0 versus 2.4 ± 0.9, P = 0.021). In ICD patients, IAT can be predicted using simple parameters of increased sympathetic activity such as increased maximal heart rate and increased LF/HF ratio during and after the exercise stress test.

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Cardiac fibrosis is an important process of myocardial remodeling. Connective tissue growth factor (CTGF) is a cytokine that plays a key role in the occurrence of progressive fibrosis and excessive scarring. CTGF levels are increased in the failing heart. In addition, sympathetic nerve activity is enhanced in the failing heart, and exacerbates heart failure. To clarify the relation between cardiac sympathetic nerve activity and CTGF, we studied 35 (M/F = 28/7 patients) aged 57 ± 15 years with dilated cardiomyopathy (DCM). Cardiac sympathetic nerve activity was estimated from the total defect score (TDS) and from the H/M ratio and washout rate (WR) on I-123-MIBG imaging. Cardiac symptoms (NYHA class), exercise capacity (specific activity scale: SAS), brain natriuretic peptide (BNP), hemodynamics, and CTGF were assessed. There was a significant correlation between the CTGF and WR on I-123-MIBG (r = 0.45, P = 0.008). Also, a higher plasma CTGF level was associated with a lower SAS score (r = 0.51, P = 0.002), but not the TDS, H/M ratio, or BNP concentration. Moreover, a higher NYHA class and pulmonary artery wedge pressure were associated with a higher plasma CTGF level. The plasma CTGF level can be strongly related with cardiac sympathetic nerve activity in heart failure in DCM patients.

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Since early intervention using corticosteroids improves prognosis in some patients with cardiac sarcoidosis, early and accurate diagnosis of this clinical condition is important. However, it is still not easy to evaluate the activity of cardiac sarcoidosis in clinical practice. The aim of this study was to determine whether high-sensitive cardiac troponin T (hscTnT) is useful as an additional parameter to standard assessment in patients with cardiac sarcoidosis. Twelve patients who were diagnosed as having cardiac sarcoidosis at our institution were retrospectively studied. Evaluation of patients included clinical examinations, electrocardiography, echocardiography, 67-gallium-citrate (Ga) scintigraphy, ¹⁸F-fluoro2-deoxyglucose positron emission tomography (¹⁸F-FDG PET) and laboratory data including hs-cTnT, angiotensin-converting enzyme (ACE), lysozyme and B-type natriuretic peptide (BNP). The activity of cardiac sarcoidosis was judged mainly by using ¹⁸F-FDG PET. Localized uptake of ¹⁸F-FDG, which was considered to be active cardiac sarcoidosis, was seen in 8 patients. Based on the findings of ¹⁸F-FDG PET, hs-cTnT was considered to be a reliable parameter: sensitivity and specificity were 87.5% and 75.0%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) were 87.5% and 75.0%, respectively. On the other hand, these values in lysozyme and BNP markers were not as high as those in hs-cTnT. Although an ACE marker and Ga-67 scintigraphy showed specificity and PPV of 100%, both sensitivity and NPV were less than 50%. Furthermore, hs-cTnT levels decreased after steroid therapy in some patients. Hs-cTnT seems to be a useful marker for evaluating the activity of cardiac sarcoidosis.

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The purpose of this study was to investigate the precise pattern of stroke volume (SV) response during exercise in patients with chronic heart failure (CHF) compared with age-matched controls. Fourteen patients with CHF and 7 controls performed symptom-limited bicycle exercise testing with respiratory gas exchange measurement. Patients were classified into group A (n = 7) with peak VO₂ ≥18.0 mL/kg/minute and group B (n = 7) with peak VO₂ < 18.0 mL/kg/ minute. SV and cardiac output (CO) were continuously measured during exercise using a novel thoracic impedance method (Physioflow). CO and SV were lower in the group B patients than those in controls at peak exercise [CO: 11.3 ± 1.0 (SE) versus 15.6 ± 0.9 L/minute, P < 0.05, SV: 89 ± 6 versus 110 ± 6 mL, P < 0.05]. SV reached its peak levels during submaximal exercise and remained close to the peak value until peak exercise in 6 of 7 group B patients (86%). On the other hand, it progressively increased until peak exercise in 6 of 7 controls (86%) and 5 of 7 group A patients (71%). In all subjects, CO at peak exercise was more closely correlated with SV at peak exercise (r = 0.86, P < 0.001) than with peak heart rate (r = 0.69, P < 0.001). CHF patients with impaired exercise capacity had attenuated increment of CO during exercise, and SV reached its peak levels during submaximal exercise.

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Left ventricular diastolic dysfunction (LVDD) develops in the early stages of acromegaly. The purpose of this study was to identify LVDD analyzing by new echocardiograpic criteria as well as to evaluate determinants of the LVDD in acromegaly. This cross-sectional study examined 42 patients with acromegaly; 16 in active disease (AA) and 26 cured/ well controlled (CA), and compared them with 30 healthy controls (CG). Ventricular systolic and diastolic functions were studied by conventional and tissue Doppler imaging based on the E/Em ratio and myocardial performance index (MPI). Other clinical parameters possibly contributing to LVDD in acromegaly were also investigated. The prevalence of LV hypertrophy (33%) and LVDD (35.7%) were increased in acromegaly, however, there were no differences between the AA and CA groups. Acromegalic patients had higher LV volumes and LV mass, and septal E/Em ratio compared to CG, whereas LV ejection fraction and MPI were not different. The presence of acromegaly (r = 0.29, P = 0.013), diabetes mellitus (DM) (r = 0.41, P < 0.001), hypertension (r = 0.35, P = 0.002), and sleep apnea (r = 0.56, P = 0.003) were found to be correlated with LVDD, whereas duration and activity of acromegaly were not. In regression analysis, advanced age (OR: 8.53, P = 0.006) and DM (OR: 25.9, P = 0.007) were found to be independent risk factors for LVDD. The risk of LVDD according to new criteria increases in acromegaly. However, it seems to be related to the presence of DM and advanced age and is independent of disease duration and activity.

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The purpose of this study was to determine whether high sensitivity C-reactive protein (hsCRP) before cardiac re-synchronization therapy (CRT) implantation was able to predict the response to CRT and cardiac deaths in severe heart failure patients. The study population consisted of 65 heart failure patients (46 males, mean age 65.0 ± 11.8 years, NYHA class III/IV) with CRT implantation. Levels of hsCRP and B-type natriuretic peptide (BNP) were measured before CRT implantation. Left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), and left ventricular ejection fraction (LVEF) were assessed by echocardiography at the same time. At 6 months after device implantation follow-up, echocardiography was performed and reverse remodeling was defined as > 15% reduction in LVESV. Of the 61 patients (4 patients died within 6 months), 41 patients (67%) and 20 patients (33%) were classified as responders (group-R) and nonresponders (group-NR), respectively. Cardiac deaths occurred more frequently in group-NR than in group-R (29% versus 5%, P < 0.05). Hs-CRP level was significantly higher in group-NR than in group-R (P < 0.01). Multivariate logistic regression analysis showed an independent relationship between hsCRP and the incidence of nonresponders (odds ratio: 1.499, P = 0.011). Stepwise multivariate Cox proportional hazard analysis identified the hsCRP level as the strongest predictive factor for cardiac death (hazard ratio: 1.337, P = 0.001). Receiver operating characteristic (ROC) analysis revealed hsCRP levels of 3.0 mg/L as the cut-off value for cardiac mortality. The hsCRP level may provide a new insight into CRT implantation for severe heart failure by predicting responses to CRT and cardiac death.

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The relationship between the short-term prognosis of acute heart failure (AHF) and acute kidney injury (AKI) using the risk, injury, failure, and end stage (RIFLE) criteria has already been reported, however, the relationship between the long-term prognosis and AKI has not. We investigated the relationship between the long-term prognosis after discharge and AKI using the RIFLE criteria. Five hundred patients with AHF admitted to our intensive care unit were analyzed. Patients were assigned to a no AKI (n = 156), Class R (risk; n = 201), Class I (injury; n = 73), or Class F (failure; n = 70) using the most severe RIFLE classifications during hospitalization. We evaluated the relationships between the RIFLE classifications and any-cause death, and HF events including death and readmission for HF within 1 year. A multivariate logistic regression model found that Class I (P = 0.013, OR: 2.768; 95% CI: 1.236-6.199) and Class F (P < 0.001, OR: 7.920; 95% CI: 3.497-17.938) were independently associated with any-cause death, and Class F was associated with HF events (P = 0.001, OR: 3.486; 95% CI: 1.669-7.281). The Kaplan-Meier survival curves showed the prognosis, including death, to be significantly poorer in Class I than in no AKI and Class R, to be significantly poorer in Class F than in no AKI, Class R, and Class I, and the prognosis including HF events to be significantly poorer in Class F than in no AKI, Class R, and Class I. The presence of severe AKI (Class I and F) was independently associated with long-term mortality for AHF.

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Rapid measurement of B-type natriuretic peptide (BNP) plays a practical role in the diagnosis of congestive heart failure. Analytical evaluation of a new small-footprint immunochromatography reader of BNP (Rapidpia^® ) was performed and compared with the commercially available SHIONOSPOT^® Reader as the index. The new BNP assay had a within-run coefficient of variation (CV) of 9.0% and a between-run CV of 2.1%. Correlations between whole blood and plasma samples and those with the index SHIONOSPOT^® Reader were y = 0.93x + 0.88, R² = 0.98 and y = 1.08x - 6.67, R² = 0.93, respectively. Based on our findings, the two point-of care (POC) assays for BNP, Rapidpia^® and SHIONOSPOT^® Reader, showed comparable results.

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Although a relationship between periodontitis and myocardial hypertrophy has been reported, the precise mechanism has not been clarified. The purpose of this study was to investigate the association between periodontal infection and myocardial hypertrophy. Transverse aortic constriction (TAC) was performed. Mice were injected with Aggregatibacter actinomycetemcomitans (A.a.) (0.1 mL of 10⁸ CFU/mL) in the infected group and PBS in the control group. Echocardiography, histopathology, and immunohistochemistry were performed. Echocardiography indicated that left ventricular fractional shortening had decreased in the infected group compared to the control group on day 28. Heart to body weight ratio increased in the infected group compared to the control group. Histopathologically, A.a.-infected mice showed markedly enhanced cardiac hypertrophy, fibrosis and arteriosclerosis 4 weeks after TAC operation. Immunohistochemistry revealed that expression of MMP-2 in the interstitial tissue was enhanced in the infected group. These results suggested that the periodontal pathogen caused a deterioration of pressure overload-induced myocardial hypertrophy through MMP activation.

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Vascular calcification is an active and regulated process that is similar to bone formation. While calcium channel blockers (CCBs) have been shown to improve outcomes in atherosclerotic vascular disease, it remains unknown whether CCBs have an effect on the process of vascular calcification. Here we investigated whether CCBs inhibit osteogenic differentiation and matrix mineralization of vascular smooth muscle cells induced by Msx2, a key factor of vascular calcification. Human aortic smooth muscle cells (HASMCs) were transduced with adenovirus expressing MSX2 and were treated with 3 distinct CCBs. Azelnidipine, a dihydropyridine subclass of CCBs, significantly decreased alkaline phosphatase (ALP) activity of Msx2-overexpressed HASMCs, whereas verapamil and diltiazem had no effect. Furthermore, azelnidipine, but not verapamil and diltiazem, significantly decreased matrix mineralization of Msx2-overexpressing HASMCs. Azelnidipine significantly attenuated the induction of ALP gene expression by Msx2, a key transcription factor in osteogenesis, while it did not reduce enzymatic activity of ALP. Furthermore, azelnidipine inhibited the ability of Msx2 to activate the ALP gene, but had no effect on Notch-induced Msx2 expression. Given that L-type calcium channels are equally blocked by these CCBs, our results suggest that azelnidipine inhibits the Msx2-dependent process of vascular calcification by mechanisms other than inhibition of calcium channel activity.

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Announcement of Retraction
The editorial office of International Heart Journal has recently confirmed that the clinical study written by Masataka Yoda, et al published in the March 2008 issue of International Heart Journal (Int Heart J 2008; 49: 213-220), was a duplicate publication, which violates the prepublication agreement that any submission to IHJ should be the first publication on an ex-clusive basis. Therefore, we hereby notify our readers that the paper has been retracted.

Ryozo Nagai, MD
Editor-in-Chief
International Heart Journal

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