Accuracy of aortic valve calcification volume score for identification of significant aortic stenosis on non-electrocardiographic-gated computed tomography compared to the Agatston scoring system.

BACKGROUND: Considering the absence of reports validating the precision of the volume score and the relationship between the volume and Agatston scores, this study evaluated the accuracy of the volume score compared to the Agatston score for the quantitative measurement of aortic valve calcification (AVC) on non-electrocardiographic-gated computed tomography (CT). METHODS: We retrospectively analysed the AVC scores of 5385 patients who underwent transthoracic echocardiography between March 1, 2013 and December 26, 2019 â€‹at our institution, using non-contrast non-electrocardiographic-gated CT. The thresholds for significant aortic stenosis (AS) were computed using receiver operating characteristic curves based on the AVC scores. The area under the curve (AUC) of the Agatston and volume scores for significant AS were compared to evaluate the accuracy of the scoring method. RESULTS: All sex-specific AVC thresholds of the volume score for significant AS (moderate and high AS severity, moderate and high AS severity without discordance, discordant severe AS, and concordant severe AS) showed high sensitivity and specificity (AUC, 0.978-0.996; sensitivity, 94.2-98.4%; specificity, 90.1-100%). No significant differences in the AUC were observed between the Agatston and volume scores for significant AS in male and female patients. CONCLUSION: All volume score threshold values showed high sensitivity and specificity for identifying significant AS. The accuracy of the test for AVC thresholds of the volume score for significant AS was comparable to that of the Agatston score. Our findings raise questions about the significance of weighting calcium density in the Agatston score for assessing AS severity.

Prediction of spontaneous echocardiographic contrast within the left atrial appendage in cardiac computed tomography of patients with atrial fibrillation.

This study aimed to assess the predictors of spontaneous echocardiographic contrast (SEC) using left atrial appendage (LAA) findings in cardiac computed tomography (CT) of patients with atrial fibrillation (AF). We retrospectively analyzed cardiac CT findings of the LAA, including morphology, volume, and filling defects, of 641 patients who underwent transesophageal echocardiography (TEE) prior to pulmonary vein isolation (PVI) from January 6, 2013 through December 16, 2019 at our institution. We investigated potential associated factors that might be predictors of SEC using cardiac CT findings and computed a receiver operator characteristic, choosing a threshold value at which the likelihood of SEC could be predicted based on the LAA volume indexed for body size. SEC correlated significantly with indexed LAA volume (P < 0.001; odds ratio [OR], 1.31; 95% confidence interval [CI], 1.17-1.48) of 7.75 cm3/m2 or greater (sensitivity, 76.0%; specificity, 57.7%), LAA early filling defect (P = 0.005; OR, 2.72; 95% CI, 1.35-5.48), a history of persistent AF (P < 0.001; OR, 3.81; 95% CI, 1.86-7.80), and LAA flow velocity (P < 0.001; OR, 0.97; 95% CI, 0.96-0.99). Findings of LAA in cardiac CT can allow for the noninvasive estimation of SEC to determine the need for additional TEE investigation and the need to obtain additional information for risk stratification and management of thromboembolic events in patients with AF.

Optimal threshold score of aortic valve calcification for identification of significant aortic stenosis on non-electrocardiographic-gated computed tomography.

OBJECTIVES: This study evaluated the association between aortic valve calcification (AVC) and aortic stenosis (AS) by scoring the AVC to determine the threshold scores for significant AS on non-electrocardiographic (ECG)-gated computed tomography (CT). METHODS: We retrospectively analyzed the AVC scores of 5385 patients on non-contrast non-ECG-gated CT, who underwent transthoracic echocardiography (TTE) from March 1, 2013, to December 26, 2019, at our institution. Multivariable logistic regression models were used to identify potential risk factors for significant AS. The thresholds for significant AS were computed using receiver operator characteristic (ROC) curves, based on the AVC scores after propensity score matching. RESULTS: A significant association was found between AS and age (p < 0.001; odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.06), female sex (p < 0.001; OR, 4.5; 95% CI, 2.75-7.36), bicuspid aortic valve (p < 0.001; OR, 23.2; 95% CI, 7.35-72.9), and AVC score (AVC score/100) (p < 0.001; OR, 1.82; 95% CI, 1.71-1.95). All sex-specific AVC thresholds for significant AS (moderate and over AS severity, moderate and over AS severity without discordance, discordant severe AS, and concordant severe AS) showed high sensitivity and specificity (AUC, 0.939-0.968; sensitivity, 84.6-96%; specificity, 84.2-97.1%). CONCLUSIONS: We determined the optimal AVC threshold scores for significant AS, which may aid in diagnosing significant asymptomatic AS on incidental detection of AVC through non-ECG-gated CT for non-cardiac indications. KEY POINTS: • Increased frequency of non-electrocardiographic (ECG)-gated computed tomography (CT) for non-cardiac indications has led to the increased incidental identification of aortic valve calcification (AVC). • It is important to identify patients with significant aortic stenosis (AS) who require additional echocardiographic assessment on incidental detection of AVC via non-ECG-gated CT. • We determined the AVC thresholds with high sensitivity and specificity to identify significant AS on non-ECG-gated CT, which could lead to early diagnosis of asymptomatic significant AS and improved prognosis.

The role of native T1 values on the evaluation of cardiac manifestation in Japanese Fabry disease patients.

Aims: T1 mapping in cardiac magnetic resonance imaging enables us to distinguish various myocardial diseases showing left ventricular hypertrophy. Fabry disease is a lysosomal storage disorder causing the accumulation of glycosphingolipids into various organs, including the heart, which can be detected by native T1 values in T1 mapping. However, there is no report for the systematic evaluation of native T1 values in Fabry disease in Japan. Methods and results: We analyzed native T1 values of 30 Fabry disease patients (14 males and 16 females) obtained by 3-T cardiac magnetic resonance imaging. Averaged T1 values were significantly lower in male patients (septal T1: 1149.5 ± 63.3 ms; total T1: 1145.1 ± 59.5 ms) than in female patients (septal T1: 1210.5 ± 45.5 ms; total T1: 1198.8 ± 51.8 ms) (p < 0.01). We compared the native T1 values of Fabry disease patients with those obtained from 15 hypertrophic cardiomyopathy patients (9 males and 6 females). Native T1 values effectively differentiate Fabry disease from hypertrophic cardiomyopathy (septal T1: sensitivity 93.3% and specificity 80.0%; total T1: sensitivity 86.7% and specificity 73.3%). In addition, native T1 values had a significant negative correlation with the left ventricular mass index in male patients at the pre-hypertrophic stage (p < 0.05). In male and female patients without late-gadolinium enhancement, native T1 values also had a significant negative correlation with the left ventricular mass index (p < 0.05). Conclusion: These results suggest that native T1 values can be used to discriminate Fabry disease from hypertrophic cardiomyopathy and can reflect the accumulation of glycosphingolipids in cardiomyocytes.

Computed tomography findings associated with the reduction in left atrial appendage flow velocity in patients with atrial fibrillation.

The reduction in flow velocity within the left atrial appendage (LAAFV) is associated with a high risk of thromboembolic events. There has been few reports using sufficient sample size about the relationship between LAAFV reduction and LAA features on cardiac computed tomography (CT), including LAA volume and filling defects, in patients with atrial fibrillation (AF). We evaluated the predictors of reduced flow velocity within the LAA using the findings of cardiac CT in patients with AF. We retrospectively analysed the cardiac CT findings of the LAA of 440 patients who underwent transoesophageal echocardiography prior to pulmonary vein isolation between 12 February, 2013 and 16 December, 2019 at our institution. We investigated the potential predictors of reduced LAAFV and the difference in LAAFV between the different morphological types of the LAA. The reduced flow velocity within the LAA was significantly correlated with higher CHADS2 scores [P = 0.001; odds ratio (OR), 1.52; 95% confidence interval (CI), 1.18-1.95], early filling defect in the LAA (P = 0.001; OR, 3.36; 95% CI 1.63-6.93), and increased indexed LAA volume (P = 0.036; OR, 1.09; 95% CI 1.01-1.19). The LAA morphological type and AF type were not significant predictors of the LAAFV reduction. Increased LAA volume, early filling defects in the LAA, and higher CHADS2 scores were independent predictors of LAAFV reduction in patients with AF. Our findings suggest that cardiac CT findings might allow non-invasive estimation of reduced LAAFV. These CT-derived parameters may provide additional information for the risk stratification and management of thromboembolic events in patients with AF.

Filling defects in the left atrial appendage restricted to the early phase of cardiac computed tomography as a potential risk of left atrial appendage dysfunction.

BACKGROUND: Filling defects within the left atrial appendage (LAA) restricted to the early phase of computed tomography (CT) are not highly specific to the presence of thrombosis. The true significance of LAA early filling defects without thrombus remains uncertain. We evaluated the predictors of LAA early filling defects on echocardiography and cardiac CT findings in patients with atrial fibrillation (AF). METHODS: Cardiac CT findings of 641 patients with AF who underwent transesophageal echocardiography prior to pulmonary vein isolation from 6 January 2013 to 16 December 2019 at our institution were retrospectively analyzed. We investigated potential predictors of LAA early filling defects and computed the receiver operator characteristics, choosing a threshold value at which the likelihood of LAA early filling defects could be predicted. RESULTS: Early filling defects within the LAA correlated significantly with a history of persistent AF [p = 0.014; odds ratio (OR), 2.36; 95% confidence interval (CI), 1.19-4.66), low left ventricular ejection fraction (p = 0.009; OR, 2.62; 95% CI, 1.28-5.38), diminished LAA flow velocity (p < 0.001; OR, 0.97; 95% CI, 0.96-0.99) below 45.3 cm/s (sensitivity, 63.6%; specificity, 72.4%), and increased indexed LAA volume (p = 0.001; OR, 1.18; 95% CI, 1.07-1.30) ≥7.64 cm3/m2 (sensitivity, 70.5%; specificity, 69.0%). CONCLUSION: Early filling defects within the LAA on cardiac CT were associated with LAA function including risk factors for thrombus development, which could lead to noninvasive estimation of LAA function and additional information for risk stratification of thromboembolic events in patients with AF.

Characteristics of the Electrocardiogram in Japanese Fabry Patients Under Long-Term Enzyme Replacement Therapy.

Objective: An electrocardiogram (ECG) is an important tool for demonstrating cardiac manifestations in various heart diseases. The present study clarified the characteristics of ECG parameters in Japanese Fabry patients under long-term enzyme replacement therapy (ERT). Methods: We analyzed the ECGs of 40 Fabry patients (male, n = 17; female, n = 23) before and after treatment with ERT. To evaluate the atrio-ventricular conduction, the PQ interval, corrected PQ and PQ minus P-wave in lead II (Pend-Q) were calculated. The QRS duration, QTc, Sokolow-Lyon index, and strain pattern were also examined. Results: At the baseline, the shortening of the PQ interval, corrected PQ and Pend-Q was identified in 7.5, 25.0, and 47.5% of cases, respectively. The prolongation of QRS duration and QTc was found in 7.5 and 40.0% of cases, respectively. The strain pattern was mainly identified in female patients, irrespective of left ventricular hypertrophy (LVH). During long-term ERT, the PQ interval, corrected PQ and Pend-Q did not change significantly. The QRS duration was significantly prolonged in both genders, whereas the QTc was significantly prolonged only in male patients. A subgroup analysis revealed that the prolongation of the QRS duration and QTc only occurred in male patients with LVH and only occurred in female patients with the classical type mutation. The prevalence of the strain was significantly increased only in male patients with LVH. Conclusions: These results suggest that the shortening of the Pend-Q is a specific finding in Japanese Fabry patients, and the strain pattern without LVH in female patients can be considered Fabry disease. During long-term ERT, prolongation of the QRS duration and QTc can indicate the progression of myocardial damage in male patients with LVH and in female patients with the classical type mutation.

Clinical findings of gadolinium-enhanced cardiac magnetic resonance in Fabry patients.

BACKGROUND: Fabry disease is one of the causes of left ventricular hypertrophy (LVH) and can be treated with enzyme replacement therapy or pharmacological chaperone therapy. Late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR) can identify myocardial fibrosis and be used for the stratification in LVH. However, the details of the prevalence and characteristics of LGE in Japanese Fabry patients have not been reported. METHODS: We evaluated myocardial involvement in 26 Fabry patients (10 males, 16 females) using gadolinium-enhanced CMR. LGE areas were analyzed using the previously reported scoring method. Echocardiography was also performed to evaluate the left ventricular function and left ventricular mass. RESULTS: LGE on CMR images was positive in 5 out of 26 patients, and all patients with LGE-positive findings suffered from LVH (2 out of 5 male patients and 3 out of 4 female patients with LVH on echocardiography). LGE was specifically localized at the mid-wall in the infero-lateral area of the left ventricle. LGE-positive patients seemed to be older, and tended to have a larger left ventricular mass index and higher B-type natriuretic peptide level than LGE-negative patients. CONCLUSIONS: These results revealed that specific localization of LGE was present in Fabry patients.

Inflammation enhanced X-irradiation-induced colonic tumorigenesis in the Min mouse.

Inflammation is potential risk factor of various human malignancies. Inflammatory bowel syndromes such as ulcerative colitis are well known as risk factors for colon cancer. Here, we examined enhancing effects of dextran sulfate sodium (DSS)-associated inflammation on X-irradiation induced colonic tumorigenesis in Min and wild-type (WT) mice. Animals were X-irradiated at 1.5 Gy at 5 weeks of age (at 0 experimental week) and 2% DSS in drinking water was administered at 5 or 11 experimental weeks. Mice were sacrificed at 16 weeks and incidence and multiplicity of colonic tumors were assessed. Incidence of colonic tumors in Min mouse was increased from 33.3% to 100% (p<0.05) with X-irradiation alone, whereas no tumors were developed in WT mice. In DSS-treated Min mice, X-irradiation increased the number of colonic tumors. Total number of colonic tumors was increased 1.57 times to 30.7±3.83 tumors/mouse with X-irradiation+DSS at 5 weeks comapared to 19.6±2.9 in corresponding DSS alone group (p<0.05). When the duration of inflammation was compared, longer period of DSS effect promoted more colonic tumorigenesis. Collectively, we conclude that X-irradiation and DSS-induced inflammation act synergistically for colonic tumorigenesis.

Scoring of late gadolinium enhancement in cardiac magnetic resonance imaging can predict cardiac events in patients with hypertrophic cardiomyopathy.

BACKGROUND: Late gadolinium enhancement (LGE) of cardiac magnetic resonance imaging (MRI) represents myocardial fibrosis and may be related to the clinical outcome of various heart diseases. This study evaluated the relationship between LGE and cardiac events in hypertrophic cardiomyopathy (HCM) using a new scoring method. METHODS AND RESULTS: This study retrospectively followed 46 HCM patients without heart failure symptoms for 3.8 ± 1.8 years. Gadolinium-enhanced cardiac MRI was performed in all patients. Cardiac events including newly developed heart failure or ventricular tachyarrhythmia were evaluated during the follow-up period. We evaluated the predictive factors to identify the patients with cardiac events. None of the risk factors reported to be related to poor outcome or the existence of LGE alone could predict cardiac events, which might be due to the small number of subjects investigated in this study. A new scoring method for LGE-positive areas (LGE score) was applied and higher LGE score can predict cardiac events in this study population. CONCLUSIONS: The proposed LGE score for cardiac MRI is considered to be a potentially valid method for assessing cardiac events in HCM patients.

Completion of mitral isthmus ablation using a steerable sheath: prospective randomized comparison with a nonsteerable sheath.

BACKGROUND: Although mitral isthmus (MI) ablation in atrial fibrillation (AF) patients has been shown to be an effective ablative strategy, the establishment of the bidirectional conduction block of the MI is technically challenging. We investigated the usefulness of a steerable sheath for MI ablation in patients with persistent AF and its impact on the clinical outcome of persistent AF ablation. METHODS: A total of 80 consecutive patients undergoing MI ablation were randomized to 1 of the following 2 groups: group S (using a steerable long sheath) or group NS (using a nonsteerable long sheath). MI ablation was performed by using an open-irrigated ablation catheter with the guidance of a 3-dimensional mapping system. The endpoint of the MI ablation was the achievement of a bidirectional block. RESULTS: Bidirectional block through the MI was achieved in 87.5% (70/80) of patients with 14.0 ± 6.7 minutes of radiofrequency application. The bidirectional block was more frequently achieved in patients in group S compared to group NS (97.5% (39/40) vs 77.5% (31/40), P = 0.02). Additionally, epicardial ablation within the coronary sinus was less frequently required in group S compared to group NS (12.5% (5/40) vs 72.5% (29/40), P < 0.0001). Atrial tachycardia after the procedure more frequently occurred in the patients in whom MI block had not been achieved during the initial procedure (40.0% (4/10) vs 10.0% (7/70), P = 0.04). CONCLUSIONS: The MI block could be achieved in the majority of patients by using a steerable sheath. An incomplete MI block increased the risk of AT following persistent AF ablation.

Influence of low-grade inflammation on plasma B-type natriuretic peptide levels.

OBJECTIVE: B-type natriuretic peptide (BNP) is a cardiac hormone. The results of previous in vitro studies suggest that neurohumoral factors, and not only hemodynamic factors, may cause BNP secretion. In this study, we examined the impact of serum C-reactive protein (CRP) levels on the relationship between echocardiographic parameters and plasma BNP levels in patients with cardiovascular diseases. METHODS AND PATIENTS: The study population comprised 417 patients who visited our cardiovascular unit with a problem. Both blood sampling and echocardiography were performed within one month. RESULTS: Multiple regression analysis showed that plasma BNP levels were negatively correlated with male gender, body mass index, and estimated glomerular filtration rate, and positively correlated with serum CRP levels and left ventricular end-systolic dimension (LVDs). The study population was divided into two groups based on the 75th percentile of the serum CRP levels. Single regression analysis showed that a regression line between LVDs and plasma BNP levels was steeper in the group of patients with CRP levels above the 75th percentile. Multiple regression analysis revealed that the interaction term (LVDs×CRP) was significant, which means LVDs had more impact on plasma BNP levels at higher CRP levels. CONCLUSION: Plasma BNP levels increased with respect to the severity of cardiac dysfunction and serum CRP levels, and should therefore be considered a collective or total marker for life-threatening conditions including systemic inflammation, and not simply as a marker of cardiac dysfunction in patients with cardiovascular diseases.

[Ultrasonographic assessment of carotid atherosclerosis for the differentiation of ischemic cardiomyopathy and dilated cardiomyopathy].

OBJECTIVES: We assessed the clinical value of carotid intima-media thickness (IMT) for the differentiation of ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM). METHODS: We studied 38 patients who showed left ventricular dilation and low ejection fraction (< 40%) by cardiac catheterization. There were 15 patients with ICM which was defined as stenosis of > 75% at one major branch or more. Twenty-three patients were found to have DCM as diagnosed by histological examination using biopsy specimens. Carotid IMT visualized by B-mode imaging was measured at 16 sites in the extracranial carotid arteries, and the maximum IMT, mean IMT, and plaque score were calculated. These parameters together with cardiovascular risk factors including age, sex, hypertension, diabetes mellitus, hypercholesterolemia, cigarette smoking, and obesity were compared between the ICM and the DCM groups. RESULTS: The maximum IMT, mean IMT, and plaque score in the ICM group were 2.80 +/- 1.63 mm, 1.21 +/- 0.36 mm, 13.05 +/- 8.12, respectively, which were significantly higher than the corresponding parameters in the DCM group (1.19 +/- 0.51 mm, 0.73 +/- 0.15 mm, 1.52 +/- 2.51; p < 0.001, respectively). Furthermore, plaque score of greater than 5 was found to be an excellent diagnostic parameter for ICM with 91% sensitivity and 100% specificity. The cardiovascular risk factors did not differ between the two groups. CONCLUSIONS: Our observations demonstrate that assessment of carotid IMT is a clinically useful tool to differentiate ICM and DCM in patients with left ventricular dysfunction. In particular, coronary angiography should be recommended in patients with a plaque score of greater than 5.