Additive prognostic significance of ejection fraction for ESC risk model in hypertrophic cardiomyopathy patients.

The European Society of Cardiology (ESC) clinical risk model is reported in predicting sudden death of hypertrophic cardiomyopathy (HCM). We examined the validity of this model and investigated the significance of ejection fraction (EF) in predicting the prognosis using ESC risk model in HCM patients. 305 HCM patients (198 males) were followed (median follow-up 4.8 years) for life-threatening arrhythmic events (sudden death, aborted sudden death, sustained VT/VF, appropriate ICD intervention for VT/VF) and were divided using ESC risk model into low- (Group L), intermediate- (Group I) and high- (Group H) risk groups. There was a significant difference in the events rate among the 3 groups (L, 0.9%/year; I, 3.9%/year; H, 6.8%/year; log-rank p < 0.001) in all study patients. Reduced EF (<50%) was identified in 27 (8.9%) cases. There was a significant difference in the events rate among the 3 groups in patients with reduced EF (L, 2.4%/year; I, 4.9%/year; H, 16.1%/year; log-rank p = 0.025). There was a significant difference in the events rate among 2 groups in patients stratified as Group H (preserved EF, 3.1%/year vs. reduced EF, 16.1%/year; log-rank p = 0.041). ESC risk model precisely predicts life-threatening events in patients with HCM. Adding EF to ESC risk model are useful for further risk stratification of life-threatening arrhythmic events.

High Signal Intensity on T2-Weighted Cardiovascular Magnetic Resonance Imaging Predicts Life-Threatening Arrhythmic Events in Hypertrophic Cardiomyopathy Patients.

BACKGROUND: The prognostic value of high signal intensity on T2-weighted cardiovascular magnetic resonance imaging (T2 high signal) in hypertrophic cardiomyopathy (HCM) patients in a single-center cohort was investigated.Methods and Results:A total of 237 HCM patients (median age, 62 years; 143 male) underwent T2-weighted, cine and late gadolinium enhancement (LGE) imaging, and were followed (median duration, 3.4 years) for life-threatening arrhythmic events. The clinical and magnetic resonance imaging characteristics were extracted, and predictors of life-threatening arrhythmic events were assessed on multivariate analysis. LGE was present in 180 patients (75.9%). Median LGE score was 3 in a left ventricle 17-segment model. T2 high signal was present in 49 patients (20.7%). The annual events rate was significantly higher in patients with extensive LGE (score ≥4) than in those without (3.0%/year vs. 0.5%/year, P=0.011). On multivariate analysis, extensive LGE (hazard ratio, 5.650; 95% CI: 1.263-25.000, P=0.024) as an independent predictor for life-threatening arrhythmic events. In patients with extensive LGE, the annual events rate was significantly higher in patients with T2 high signal than in those without (5.8%/year vs. 0.9%/year, P=0.008). CONCLUSIONS: Extensive LGE was an independent predictor of life-threatening arrhythmic events in HCM patients. Furthermore, T2 high signal is useful for the risk stratification of serious arrhythmic events in patients with extensive LGE.

Prognostic value of cardiovascular magnetic resonance imaging for life-threatening arrhythmia detected by implantable cardioverter-defibrillator in Japanese patients with hypertrophic cardiomyopathy.

Implantable cardioverter-defibrillator (ICD) is effective to prevent sudden death in HCM patients. We reviewed ICD records to analyze the relation between life-threatening arrhythmia and late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) in Japanese hypertrophic cardiomyopathy (HCM) patients. In 102 consecutive patients (median age 63 years, 63 males) implanted with an ICD after CMR with gadolinium enhancement (median follow-up 2.8 years), the outcome of life-threatening arrhythmic events (appropriate ICD interventions for ventricular tachycardia or ventricular fibrillation) was examined. Appropriate interventions rate were 10.3% per year for secondary prevention and 7.4% per year for primary prevention. The annualized ICD-related complication rate was 3.7%. 43/91 patients (47%) implanted ICD for primary prevention had maximum wall thickness ≥20 mm plus LGE in ≥4 of 17 left ventricular segments (cut-off value obtained from ROC curve); the appropriate ICD intervention rate was significantly higher in this group than in other patients group (annualized event rate, 11.1 vs. 4.6%; log-rank P = 0.038). A combination of myocardial hypertrophy and LGE is a useful outcome predictive factor for life-threatening ventricular arrhythmia in Japanese HCM patients.

Extent of Late Gadolinium Enhancement on Cardiac Magnetic Resonance Imaging in Japanese Hypertrophic Cardiomyopathy Patients.

BACKGROUND: In addition to the presence of late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR), the extent of LGE is considered clinically important in hypertrophic cardiomyopathy (HCM). We evaluated the extent of LGE on CMR in a large series of Japanese HCM patients. METHODS AND RESULTS: CMR was performed in 317 HCM patients (147 male). The extent of LGE was scored as the sum of LGE-positive segments in a left ventricle (LV) 17-segment model. LGE was present in 246 patients (77.6%). LGE was detected in 3.5±3.1 segments on average. When the patients were divided according to maximum wall thickness (mild, <20 mm; moderate, 20-29 mm; severe, ≥30 mm), median LGE score increased as wall thickness increased (mild, 2 vs. moderate, 4 vs. severe, 5; P=0.000). When the patients were divided according to ejection fraction (EF) (reduced, <50%; low-normal, 50-65%; normal, >65%), median LGE score increased as EF decreased (reduced, 7 vs. low-normal, 4 vs. normal, 2; P=0.000). On multivariate analysis, reduced EF (OR, 0.947, P=0.015), pressure gradient <30 mmHg (OR, 0.359, P=0.000) and increased maximum wall thickness (OR, 1.236, P=0.000) were independent factors associated with extensive LGE. CONCLUSIONS: Progression of LGE was related to increased wall thickness, decreased contractility, and reduced intraventricular pressure gradient.

Diagnostic performance of computed tomography for detection of concomitant coronary disease in hypertrophic cardiomyopathy.

OBJECTIVES: To evaluate the diagnostic performance of computed tomography (CT) in patients with hypertrophic cardiomyopathy (HCM) and suspected coexistent coronary artery diseases (CADs). METHODS: Sixty patients were enrolled in this study. Cardiac CT examination included CT coronary angiography (CTCA) and delayed enhancement CT. CT performance in evaluation of the coronary artery was assessed and compared with that of catheter-based coronary angiography (CA). The left ventricle (LV) wall thickness, functional indices and myocardial delayed enhancement (MDE) were measured via cardiac magnetic resonance (CMR) and CT images. RESULTS: Compared with catheter-based CA, CTCA produced a 100 % (24/24) sensitivity, a 94.4 % (34/36) specificity, a 92.3 % (24/26) positive predictive value and a 100 % (34/34) negative predictive value. CT-measured LV wall thickness and functional indices were correlated with those measured via CMR (P < 0.01), though the CT-measured values were smaller than the CMR-measured values. Bland-Altman analysis showed the volume of the focal MDE determined via CT was slightly smaller than that determined using CMR (mean difference: 0.3 cm(3)). CONCLUSIONS: For patients with HCM and suspected coexistent CAD, this comprehensive cardiac CT protocol can be helpful in ruling out coronary stenosis and can provide information regarding morphology, function and tissue characterization of the LV myocardium.

[Cardiovascular magnetic resonance imaging].

Cardiac magnetic resonance imaging (CMR) evolves and is occupying an important status in cardiovascular diagnostic imaging. In particular, in the estimation of the cause of heart failure, or evaluation of severity-of-illness and prognostic presumption, utility is high clinically. In this chapter, about a selection sequence for taking image according to the purpose, description of findings, and its clinical utility are introduced. And the role which this imaging plays will be discussed in the near future.

[Basic examination for three-dimensional phase-sensitive inversion recovery (3D PSIR) method by late gadolinium enhancement of non-breath-hold cardiac magnetic resonance image].

PURPOSE: We studied imaging parameters for the three-dimensional phase-sensitive inversion recovery by a late gadolinium enhancement (3D PSIR) method. METHOD: In the 3D PSIR method using a 1.5 Tesla MRI system and a polyvinyl alcohol (PVA) gel phantom, we evaluated the relation of the signal intensity at multiple inversion times (TI), 100-500 ms; flip angles (FA), 15-35°; and segments, 20-45. In 30 patients with chronic myocardial infarction, we measured and compared the late gadolinium enhancement (LGE) image area of ratio for each of 3 sections on both 3D LGE images by a non-breath hold and two-dimensional inversion recovery (2D IR) method non-breath hold. RESULT: In the 3D PSIR method, we recognized the signal intensity to make the width of step, maximum, and we recognized that the TI range, to keep the effective signal intensity difference constant, was limited on each phantom. The more this TI range decreased the bigger the difference in the FA and signal intensity. The set-up range of TI for the segment number remained the same. In the clinical setting, we recognized a good correlation between the 3D PSIR method (TI 300 ms, FA 20°) and the IR method (r=0.905, p<0.001). The imaging parameter that can be used in the clinical setting with the 3D PSIR method is FA 20° TI 200-300 ms, with the segment number adjusted by the cardiac cycle.

Significance of the second peak of systolic blood pressure for identifying both high and low cardiovascular risk states.

This study was conducted to clarify whether the second peak of the systolic blood pressure (SBP2) has significant information about cardiovascular (CV) risk state, independent of the brachial BP. SBP2 was measured by radial pressure wave analysis in 7847 Japanese subjects (50+/-10 years old), and the Framingham risk score (FRS) and general cardiovascular disease risk score were calculated (FRSgen). The results of multivariate analysis revealed that the SBP2 showed a significant correlation with the FRS (beta=0.04, t-value=3.92, P<0.01) and FRSgen (beta=0.05, t-value=6.55, P<0.01), independent of the brachial SBP. The non-standardization coefficient of SBP2 was smaller than that of brachial SBP. The logistic regression analysis showed that SBP2 (2 mm Hg per increase) had a significant odds ratio to identify not only subjects with a high risk for coronary heart disease (CHD) and general CV disease (CVDgen), but also subjects with a low risk for CHD and CVDgen, independent of the brachial SBP. However, when the analysis was limited to subjects of >or=49 years of age, SBP2 could not identify either high or low CV risk subjects. Thus, in middle-aged Japanese subjects, SBP2 may provide little, yet significant, information reflecting both high and low CV risk states, independent of the brachial BP. SBP2 seems to be more applicable for CV risk stratification in younger subjects than in older subjects.

Synergistic effect of smoking and blood pressure on augmentation index in men, but not in women.

This study was conducted in healthy Japanese subjects to examine the effects of age and gender on the relationship between the risk factors for cardiovascular disease (CVD) and augmentation index (AI), and the effects of clusters of those risk factors on AI. Radial arterial pressure wave analysis was used to obtain AI in 3675 men and 2919 women. AI was found to be higher in women than in men, and age-related increase in AI showed an attenuated curve in subjects aged >or=50 years. A step-wise multivariate linear regression analysis showed that mean blood pressure and smoking are independent significant variables related to AI in men regardless of age, and in women aged <50 years, but not in women aged >or=50 years. A general linear model univariate linear regression analysis showed that mean blood pressure and smoking had a significant interaction for their relation with AI in men, but not in women. In conclusion, among the risk factors for CVD, smoking and blood pressure were found to be independent factors related to increase in AI. Although age-related attenuation of increase in AI was confirmed in Japanese subjects, these risk factors may act to increase AI even in elderly subjects, at least in part. However, the effects of these factors on AI may differ based on gender, and these factors may act synergistically to increase AI in men. On the contrary, these factors may act independently in young women to increase AI without interaction, whereas only the blood pressure seems to increase AI in elderly women.

Frequency and distribution of late gadolinium enhancement in magnetic resonance imaging of patients with apical hypertrophic cardiomyopathy and patients with asymmetrical hypertrophic cardiomyopathy: a comparative study.

Our aim was to compare the frequency and distribution of late gadolinium enhancement (LGE) on contrast MRI between hypertrophic cardiomyopathy (HCM) patients with apical hypertrophic cardiomyopathy (APH) and those with asymmetrical septal hypertrophy (ASH). We studied 66 patients with HCM (50 men and 16 women; average age: 58.8 +/- 29.8 years) who had undergone MRI. All the MRI examinations were performed using a 1.5 T system. LGE images were acquired using the inversion recovery segmented spoiled-gradient echo and phase-sensitive inversion recovery methods. We evaluated 17 segments of the left ventricle as defined by the American Heart Association criteria for LGE determination. LGE was detected at the junction of the right ventricle and the interventricular septum in 25 (73.5%) of the 34 HCM patients with ASH and in the apex of the heart in 13 (40.6%) of the 32 patients with APH. LGE-positive areas were more widely distributed in the case of the ASH group than in the case of the APH group. The distribution of LGE was clearly different between the two groups (Fisher's exact probability test, P = 0.0068). The number of LGE-positive cases and LGE-positive segments were significantly higher in the ASH group than in the APH group and there was a significant difference in the distribution of the LGE-positive areas between the two groups. LGE was mainly detected in the hypertrophied areas of the myocardium.

Usefulness of late gadolinium enhancement combined with MRI and 67-Ga scintigraphy in the diagnosis of cardiac sarcoidosis and disease activity evaluation.

We report a case in which late gadolinium enhancement (LGE) and 67-Ga scintigraphy were useful for the diagnosis of cardiac sarcoidosis and for the evaluation of the disease activity. The patient was a 60-year-old woman who had been diagnosed as having eye sarcoidosis when she was 48. Two years previously her electrocardiogram had shown abnormalities but the coronary angiography had shown normal coronary arteries; however, an aneurysm was detected in the apical portion by left ventriculography. A II degree AV block was noted on the electrocardiogram and she was referred to us for further detailed evaluation. Since the biopsy findings of skin eruptions on both eyelids indicated an epithelial cell granuloma, she was diagnosed as having cutaneous sarcoidosis. On the 67-Ga scintigram, myocardial accumulation of gallium was recognized, and on cardiovascular magnetic resonance (CMR), LGE was recognized. She was diagnosed as cardiac sarcoidosis and steroid therapy started with 30 mg prednisolone. The myocardial accumulation of gallium on the 67-Ga scintigram disappeared after the 30th day of steroid therapy. On the other hand, no changes in LGE patterns were seen after steroid therapy. In this case, LGE was useful for the diagnosis of cardiac sarcoidosis, and 67-Ga scintigram was useful for the evaluation of the disease activity. This case shows that both imaging techniques are important for the diagnosis of cardiac sarcoidosis and evaluation of the disease.

Alpha B-crystallin mutation in dilated cardiomyopathy.

Mutations in genes for sarcomeric proteins such as titin/connectin are known to cause dilated cardiomyopathy (DCM). However, disease-causing mutations can be identified only in a small proportion of the patients even in the familial cases, suggesting that there remains yet unidentified disease-causing gene(s) for DCM. To explore the novel disease gene for DCM, we examined CRYAB encoding alphaB-crystallin for mutation in the patients with DCM, since alphaB-crystallin was recently reported to associate with the heart-specific N2B domain and adjacent I26/I27 domain of titin/connectin, and we previously reported a N2B mutation, Gln4053ter, in DCM. A missense mutation of CRYAB, Arg157His, was found in a familial DCM patient and the mutation affected the evolutionary conserved amino acid residue among alpha-crystallins. Functional analysis revealed that the mutation decreased the binding to titin/connectin heart-specific N2B domain without affecting distribution of the mutant crystallin protein in cardiomyocytes. In contrast, another CRYAB mutation, Arg120Gly, reported in desmin-related myopathy decreased the binding to both N2B and striated muscle-specific I26/27 domains and showed intracellular aggregates of the mutant protein. These observations suggest that the Arg157His mutation may be involved in the pathogenesis of DCM via impaired accommodation to the heart-specific N2B domain of titin/connectin and its disease-causing mechanism is different from the mutation found in desmin-related myopathy.

Delayed contrast enhancement in a patient with perimyocarditis on contrast-enhanced cardiac MRI: case report.

The findings of contrast-enhanced cardiac magnetic resonance imaging of a 19-year-old man with perimyocarditis in the subacute and chronic stage are presented. In perimyocarditis., it is useful to check the presence of delayed contrast enhancement to confirm the presence of the lesion and to evaluate the severity of inflammation in the acute stage as well as to determine the extent of fibrosis in the pericardium and myocardium in the chronic stage.