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Background: Anemia, a common comorbidity in older patients with heart failure (HF) and atrial fibrillation (AF), is associated with an increased risk of adverse events. This study evaluated the prognostic effects of longitudinal changes in anemia status on clinical outcomes in patients with AF., Methods and Results: We prospectively evaluated data of 1,388 patients with AF from the Hokuriku-Plus AF Registry (1,010 men; mean [±SD] age 72.3±9.7 years) and recorded the incidence of death, HF, thromboembolism, and major bleeding. Of these patients, the 1,233 for whom hemoglobin levels were available at baseline and at the 1-year follow-up were further evaluated. Patients were categorized into 3 groups based on longitudinal changes in 1-year anemia status: Group 1, AF without anemia; Group 2, AF with improved anemia; and Group 3, AF with sustained or new-onset anemia. Over the 1-5 years of follow up, the incidences of death, HF, thromboembolism, and major bleeding were significantly higher among patients with than without anemia. In addition, the incidence of death or HF was significantly higher in Group 3 than in Groups 1 and 2. Multivariate analysis revealed no anemia or improvement in anemia in 1 year as an independent predictor for a favorable prognosis for cardiovascular death and HF., Conclusions: Recovery from anemia may be associated with a favorable clinical course of AF.

Background: The prognostic effect of concomitant hypertrophic cardiomyopathy (HCM) on adverse events in patients with atrial fibrillation (AF) has not been evaluated in a multicenter prospective cohort study in Japan., Methods and results: Using the Hokuriku-Plus AF Registry, 1,396 patients with nonvalvular AF (1,018 men, 72.3±9.7 years old) were assessed prospectively; 72 (5.2%) had concomitant HCM. During a median follow-up of 5.0 years (interquartile range 3.5-5.3 years), 79 cases of thromboembolism (1.3 per 100 person-years) and 192 of heart failure (HF) (3.2 per 100 person-years) occurred. Kaplan-Meier analysis revealed that the HCM group had a significantly greater incidence of thromboembolism (P=0.002 by log-rank test) and HF (P<0.0001 by a log-rank test) than the non-HCM group. The Cox proportional hazards model demonstrated that persistent AF (adjusted hazard ratio 2.98, 95% confidence interval 1.56-6.21), the CHA 2 DS 2 -VASc score (1.35, 1.18-1.54), and concomitant HCM (2.48, 1.16-4.79) were significantly associated with thromboembolism. Conversely, concomitant HCM (2.81, 1.72-4.43), older age (1.07, 1.05-1.10), lower body mass index (0.95, 0.91-0.99), a history of HF (2.49, 1.77-3.52), and lower left ventricular ejection fraction (0.98, 0.97-0.99) were significantly associated with the development of HF., Conclusions: Concomitant HCM predicts the incidence of thromboembolism and HF in AF patients.

Background: Recently, the function of high-density lipoprotein (HDL), rather than the HDL cholesterol (HDL-C) level, has been attracting more attention in risk prediction for coronary artery disease (CAD)., Methods and results: Patients with clinically diagnosed familial hypercholesterolemia (FH; n=108; male/female, 51/57) were assessed cross-sectionally. Serum cholesterol uptake capacity (CUC) levels were determined using our original cell-free assay. Linear regression was used to determine associations between CUC and clinical variables, including low-density lipoprotein cholesterol and the carotid plaque score. Multivariable logistic regression analysis was used to test factors associated with the presence of CAD. Among the 108 FH patients, 30 had CAD. CUC levels were significantly lower among patients with than without CAD (median [interquartile range] 119 [92-139] vs. 142 [121-165] arbitrary units [AU]; P=0.0004). In addition, CUC was significantly lower in patients with Achilles tendon thickness ≥9.0 mm than in those without Achilles tendon thickening (133 [110-157] vs. 142 [123-174] AU; P=0.047). Serum CUC levels were negatively correlated with the carotid plaque score (Spearman's r=0.37; P=0.00018). Serum CUC levels were significantly associated with CAD, after adjusting for other clinical variables (odds ratio=0.86, 95% CI=0.76-0.96, P=0.033), whereas HDL-C was not., Conclusions: HDL function, assessed by serum CUC level, rather than HDL-C level, adds risk stratification information among FH patients.

Background: Recent studies suggest that cumulative exposure to low-density lipoprotein-cholesterol (LDL-C) leads to the development of atherosclerotic cardiovascular disease (ASCVD). However, few studies have investigated whether this link extends to individuals with familial hypercholesterolemia (FH), a relevant patient population., Methods and results: We retrospectively investigated the health records of 1,050 patients with clinical FH diagnosis between April 1990 and March 2019. We used Cox proportional hazards models adjusted for established ASCVD risk factors to assess the association between cholesterol-year-score and major adverse cardiovascular events (MACEs), including death from any cause or hospitalization due to ASCVD events. Cholesterol-year-score was calculated as LDL-C max × [age at diagnosis/statin initiation] + LDL-C at inclusion × [age at inclusion - age at diagnosis/statin initiation]. The median follow-up period for MACE evaluation was 12.3 (interquartile range, 9.1-17.5) years, and 177 patients experienced MACEs during the observation period. Cholesterol-year-score was significantly associated with MACEs (hazard ratio, 1.35; 95% confidence interval, 1.07-1.53; P=0.0034, per 1,000 mg-year/dL), independent of other traditional risk factors including age and LDL-C, based on cross-sectional assessment. Cholesterol-year-score improved the discrimination ability of other traditional risk factors for ASCVD events (C-index, 0.901 vs. 0.889; P=0.00473)., Conclusions: Cumulative LDL-C exposure was strongly associated with MACEs in Japanese patients with FH, warranting early diagnosis and treatment initiation in these patients.

Background: Because it is unclear whether lower urinary tract symptoms (LUTS) are associated with cardiovascular disease (CVD) in the Japanese population, we explored the association in general Japanese men aged 55-75 years., Methods and results: The cross-sectional study included male participants who had both national health checkup data and the International Prostate Symptom Score (IPSS) in the same calendar year between 2009 and 2017. LUTS severity was evaluated by IPSS. A robust Poisson regression model was used to assess the association between LUTS severity and the composite CVD outcome [coronary artery disease (CAD), stroke, or atrial fibrillation (AF)] and each component of the composite outcome. Prevalence ratio (PR) was adjusted for conventional cardiovascular risk factors. Of 16,781 male participants (mean age, 67±5 years), mild LUTS were observed in 9,243 (55.1%); moderate, 6,445 (38.4%); and severe, 1,093 (6.5%). Compared with the mild LUTS group, moderate LUTS [PR 1.18, 95% confidence interval (CI) 1.10-1.25, P<0.001] and severe LUTS (PR 1.38, 95% CI 1.24-1.53, P<0.001) were significantly associated with a higher prevalence of CVD. LUTS severity was associated with higher prevalence of CAD and stroke, but not AF., Conclusions: The severity of LUTS was associated with a higher prevalence of CVD, especially CAD and stroke, independent of conventional CVD risk factors.

Background: This study is aimed to compare the efficacy of the 2017 Japan Atherosclerosis Society (JAS) familial hypercholesterolemia (FH) criteria, which focuses on only 3 essential clinical manifestations, with that of Dutch Lipid Clinic Network (DLCN) FH criteria, which adopts a scoring system of multiple elements., Methods and results: A total of 680 Japanese dyslipidemic participants (51% men) were enrolled between 2006 and 2018, all of whom had full evaluations of low-density lipoprotein (LDL) cholesterol, Achilles tendon X-rays, family history records, and genetic analysis of FH-associated genes (LDLR,APOB, andPCSK9). Predictive values for the existence of FH mutations by both clinical criteria were evaluated. Overall, 173 FH patients were clinically diagnosed by using the 2017 JAS criteria and 100, 57, 156, and 367 subjects were also diagnosed as having definite, probable, possible, and unlikely FH by the DLCN FH criteria, respectively. The positive and negative likelihood ratio predicting the presence of FH mutations by using the 2017 JAS FH criteria were 19.8 and 0.143, respectively; whereas, using the DLCN criteria of definite, probable, and possible FH, the ratios were 29.2 and 0.489, 9.70 and 0.332, and 3.43 and 0.040, respectively., Conclusions: Among Japanese patients, the JAS 2017 FH criteria is considered superior to diagnose FH mutation-positive patients and simultaneously rule out FH mutation-negative patients compared with the DLCN FH criteria.

Background: Integrated device diagnostics, Triage-HF, is useful in risk stratifying patients with heart failure (HF), but its performance for Japanese patients remains unknown. This is a prospective study of Japanese patients treated with a cardiac resynchronization therapy defibrillator (CRT-D), with a Medtronic OptiVol 2.0 feature., Methods and results: A total of 320 CRT-D patients were enrolled from 2013 to 2017. All received HF treatment in the prior 12 months. Following enrollment, they were followed every 6 months for 48 months (mean, 22 months). Triage-HF-stratified patients at low, medium and high risk statuses at every 30-day period, and HF-related hospitalization occurring for the subsequent 30 days, were evaluated and repeated. The primary endpoint was to assess Triage-HF performance in predicting HF-related hospitalization risk. All device data were available for 279 of 320 patients (NYHA class II or III in 93%; mean left ventricular ejection fraction, 31%). During a total of 5,977 patient-month follow-ups, 89 HF-related hospitalization occurred in 72 patients. The unadjusted event numbers for Low, Medium and High statuses were 19 (0.7%), 42 (1.6%) and 28 (4.1%), respectively. Relative risk of Medium to Low status was 2.18 (95% CI 1.23-3.85) and 5.78 (95% CI 3.34-10.01) for High to Low status. Common contributing factors among the diagnostics included low activity, OptiVol threshold crossing, and elevated night heart rate., Conclusions: Triage-HF effectively stratified Japanese patients at risk of HF-related hospitalization.

Background: Few data specifically investigate associations between fasting/non-fasting triglycerides (TG) and cardiovascular (CV) events under statin therapy among Japanese diabetic patients., Methods and results: We recruited 4,988 participants with diabetes from the EMPATHY study. Median follow-up was 3 years. We evaluated associations between serum fasting/non-fasting TG and first CV events in Cox-regression hazard models adjusted by classical risk factors. CV events were defined as (1) major adverse cardiac events (MACE) including myocardial infarction, stroke, or cardiac death; and (2) CV diseases (CVD) including myocardial infarction, unstable angina, ischemic stroke, or large artery disease or peripheral arterial disease. Fasting as well as non-fasting TG were associated with MACE (adjusted hazard ratio [HR]: 1.017 per 10 mg/dL; 95% confidence interval [CI]: 1.000-1.037; P=0.046, adjusted HR: 1.028 per 10 mg/dL; 95% CI: 1.006-1.050; P=0.0091) and CVD (adjusted HR: 1.024 per 10 mg/dL; 95% CI: 1.011-1.038; P=4.4×10 -3 , adjusted HR: 1.028 per 10 mg/dL; 95% CI: 1.010-1.046; P=4.9×10 -3 ). Comparing the top quartile with the bottom quartile of non-fasting TG, adjusted HR significantly increased 5.18 (95% CI: 1.38-18.3, P=0.014) for MACE, and 2.40 (95% CI: 1.11-4.75, P=0.021) for CVD, while adjusted HR did not change when divided into quartile of fasting TG., Conclusions: Non-fasting TG could be considered as a substitute for fasting TG as a risk stratification for future CV events among Japanese diabetic patients.

Background: A substantial proportion of patients clinically diagnosed as having familial hypercholesterolemia (FH) do not manifest causative mutation(s) in the FH genes such asLDLR,APOB, andPCSK9. We aimed to evaluate the effect of rare and deleterious mutation(s) inABCG5/ABCG8on hyper-low-density lipoprotein (LDL) cholesterolemia in individuals who meet the clinical criteria for FH.Methods and Results:We compared the LDL cholesterol (LDL-C) values among 487 subjects with FH; the subjects were grouped according to the presence of mutation(s) in FH andABCG5/ABCG8genes. We identified 276 individuals with a deleterious mutation in 1 FH gene (57%, monogenic FH), but found no causative mutations in 156 individuals (32%, mutation-negative). A total of 37 individuals had deleterious mutations inABCG5orABCG8, but not in FH genes (8%,ABCG5/ABCG8mutation carriers). Among these, 3 individuals had sitosterolemia (0.6%) with double mutations. We also identified 18 individuals with deleterious mutations in an FH gene andABCG5orABCG8(4%,ABCG5/ABCG8-oligogenic FH). Subjects without mutations had significantly higher polygenic scores than those in any other groups. LDL-C levels in oligogenic FH subjects were significantly higher than in the monogenic FH subjects. Moreover, sitosterol/lathosterol levels were significantly affected by those mutations., Conclusions: The results suggested that rare and deleterious mutations inABCG5/ABCG8contribute substantially to mimicking and exacerbation of the FH phenotype.

Background: B-type natriuretic peptide (BNP) may be a predictor of stroke risk in patients with nonvalvular atrial fibrillation (NVAF); because heart failure is associated with the incidence of stroke in AF patients. However, limited data exist regarding the association between BNP at baseline and risks of thromboembolic events (TE) and death in NVAF patients. Methods and Results: We prospectively studied 1,013 NVAF patients (725 men, 72.8±9.7 years old) from the Hokuriku-plus AF Registry to determine the relationship between BNP at baseline and prognosis among Japanese NVAF patients. During the follow-up period (median, 751 days); 31 patients experienced TE and there were 81 cases of TE/all-cause death. For each endpoint we constructed receiver-operating characteristic curves that gave cutoff points of BNP for TE (170 pg/mL) and TE/all-cause death (147 pg/mL). Multivariate analysis with the Cox-proportional hazards model indicated that high BNP was significantly associated with risks of TE (hazard ratio [HR] 3.86; 95% confidence interval [CI] 1.83-8.67; P=0.0003) and TE/all-cause death (HR 2.27; 95% CI 1.45-3.56; P=0.0003). Based on the C-index and net reclassification improvement, the addition of BNP to CHA 2 DS 2 -VASc statistically improved the prediction of TE., Conclusions: In a real-world cohort of Japanese NVAF patients, high BNP was significantly associated with TE and death. Plasma BNP might be a useful biomarker for these adverse clinical events.

Background: Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) revealed a substantial variation in the extent of myocardial scarring, a pathological hallmark of hypertrophic cardiomyopathy (HCM). However, few data exist regarding the relationship between the presence of gene mutations and the extent of LGE. Therefore, we aimed to investigate whether variations in the extent of LGE in HCM patients can be explained by the presence or absence of disease-causing mutations.Methods and Results:We analyzed data from 82 unrelated HCM patients who underwent both LGE-CMR and next-generation sequencing. We identified disease-causing sarcomere gene mutations in 44 cases (54%). The extent of LGE on CMR was an independent factor for predicting mutation-positive HCM (odds ratio 2.12 [95% confidence interval 1.51-3.83], P<0.01). The area under the curve of %LGE was greater than that of the conventional Toronto score for predicting the presence of a mutation (0.96 vs. 0.69, P<0.01). Sensitivity, specificity, positive predictive value, and negative predictive value of %LGE (cutoff >8.1%) were 93.2%, 89.5%, 91.1%, and 91.9%, respectively., Conclusions: The results demonstrated that %LGE clearly discriminated mutation-positive from mutation-negative HCM in a clinically affected HCM population. HCM with few or no myocardial scars may be genetically different from HCM with a higher incidence of myocardial scars.

Background: The MILLION study, a prospective randomized multicenter study, revealed that lipid and blood pressure (BP)-lowering therapy resulted in regression of coronary plaque as determined by intravascular ultrasound (IVUS). In the present study we performed additional analysis to investigate the associated factors with regression of coronary plaque.Methods and Results:We investigated serial 3D IVUS images from 68 patients in the MILLION study. Standard IVUS parameters were assessed at both baseline and follow-up (18-24 months). Volumetric data were standardized by length as normalized volume. In patients with plaque regression (n=52), plaque volume normalized significantly decreased from 64.8 to 55.8 mm 3 (P<0.0001) and vessel volume normalized significantly decreased from 135.0 to 127.5 mm 3 (P=0.0008). There was no difference in lumen volume normalized from 70.1 to 71.8 mm 3 (P=0.27). There were no correlations between % changes in vessel volume and cholesterol or BP. On the other hand, negative correlations between % change in vessel volume and vessel volume normalized at baseline (r=-0.352, P=0.009) or plaque volume normalized at baseline (r=-0.336, P=0.01) were observed., Conclusions: The current data demonstrated that in patients with plaque regression treated by aggressive lipid and BP-lowering therapy, the plaque regression was derived from reverse vessel remodeling determined by vessel volume and plaque burden at baseline irrespective of decreases in lipids and BP.

The 81 st Annual Scientific Meeting of the Japanese Circulation Society was held in Kanazawa, Japan, on March 17-19, 2017 under a miraculously clear sky. The frontlines of healthcare and medicine are dramatically changing. Thus, "Cardiovascular Medicine for Next Generation" was chosen as the main theme of this meeting. The program was constructed around major identified issues, including renewal of our understanding of basic cardiovascular medicine, translational research, and preventive molecular medicine, all of which are anticipated to transcend the medical field over the next generation. Despite the provincial location, 15,672 participants, including more than 400 from overseas countries, attended the 3-day meeting, and there were in-depth discussions in the various sessions. In particular, to our great pleasure, Her Imperial Highness Princess Takamado kindly attended the opening ceremony and extended congratulations to us. The meeting successfully completed and we sincerely appreciate the great cooperation and support from all affiliates.

Background: The appropriate duration of prehospital cardiopulmonary resuscitation (CPR)administered by emergency medical service (EMS) providers for patients with out-of-hospital cardiac arrest (OHCA) necessary to achieve 1-month survival with favorable neurological outcome (Cerebral Performance Category 1 or 2, CPC 1-2) is unclear and could differ by age.Methods and Results:We analyzed the records of 35,709 adult OHCA patients with return of spontaneous circulation (ROSC) before hospital arrival in a prospectively recorded Japanese registry between 2011 and 2014. The CPR duration was defined as the time from CPR initiation by EMS providers to prehospital ROSC. The rate of 1-month CPC 1-2 was 21.4% (7,650/35,709). The CPR duration was independently and inversely associated with 1-month CPC 1-2 (adjusted odds ratio, 0.93 per 1-min increment; 95% confidence interval, 0.93-0.94). The CPR duration increased with age (P<0.001). However, the CPR duration beyond which the proportion of OHCA patients with 1-month CPC 1-2 decreased to <1% declined with age: 28 min for patients aged 18-64 years, 25 min for 65-74 years, 23 min for 75-84 years, 20 min for 85-94 years, and 18 min for ≥95 years., Conclusions: In patients who achieved prehospital ROSC after OHCA, the duration of CPR administered by EMS providers necessary to achieve 1-month CPC 1-2 varied by age.

Background: It has been shown that serum lipoprotein(a) [Lp(a)] is elevated in familial hypercholesterolemia (FH) with mutation(s) of the LDL receptor (LDLR) gene. However, few data exist regarding Lp(a) levels in FH with gain-of-function mutations of the PCSK9 gene., Methods and results: We evaluated 42 mutation-determined heterozygous FH patients with aPCSK9gain-of-function mutation (FH-PCSK9, mean age 52, mean LDL-C 235 mg/dl), 198 mutation-determined heterozygous FH patients with aLDLRmutation (FH-LDLR, mean age 44, mean LDL-C 217 mg/dl), and 4,015 controls (CONTROL, mean age 56, mean LDL-C 109 mg/dl). We assessed their Lp(a), total cholesterol, triglycerides, HDL-C, LDL-C, use of statins, presence of hypertension, diabetes, chronic kidney disease, smoking, body mass index (BMI) and coronary artery disease (CAD). Multiple regression analysis showed that HDL-C, use of statins, presence of hypertension, smoking, BMI, and Lp(a) were independently associated with the presence of CAD. Under these conditions, the serum levels of Lp(a) in patients with FH were significantly higher than those of the CONTROL group regardless of their causative genes, among the groups propensity score-matched (median Lp(a) 12.6 mg/dl [IQR:9.4-33.9], 21.1 mg/dl [IQR:11.7-34.9], and 5.0 mg/dl [IQR:2.7-8.1] in the FH-LDLR, FH-PCSK9, and CONTROL groups, respectively, P=0.002 for FH-LDLR vs. CONTROL, P=0.002 for FH-PCSK9 vs. CONTROL)., Conclusions: These data demonstrate that serum Lp(a) is elevated in patients with FH caused by PCSK9 gain-of-function mutations to the same level as that in FH caused by LDLR mutations.

Background:  Linear ablation of atrial flutter usually targets a 6 o'clock position on the cavotricuspid isthmus on left anterior oblique view, but the difficulty of the ablation often requires a variation in successful ablation line position from 5 to 7 o'clock., Methods and Results:  This study included 94 patients without structural heart disease. A linear lesion was created in turn at the 6, 7, and 5 o'clock positions until bidirectional block of the isthmus was completed; the final lesion was defined as the successful ablation line. The degree of counterclockwise heart rotation (CCW-HR) was evaluated in a blinded fashion according to the angle between the vertical line crossing the His bundle catheter and the line connecting the His bundle catheter and coronary sinus ostium. Successful ablation lines were obtained at the 6 o'clock position in 59 patients (63%); the 7 o'clock position in 19 patients (20%; the oldest group with a moderate radiofrequency burden); and the 5 o'clock position in the remaining 16 (17%; the youngest group with the largest radiofrequency burden). Age-related increase in CCW-HR was the only independent predictor of a more septal successful ablation line (OR, 7.1; 95% CI: 3.3-14.3; P<0.01)., Conclusions:  Variation in successful ablation line position was affected by age-related CCW-HR; its evaluation might reduce radiofrequency burden, especially in the young and elderly.

Background: Activation imaging with 3-dimensional speckle-tracking echocardiography (3D-STE) aims to visualize the time required for the onset of regional contraction from QRS onset. We hypothesized that the optimal setting of activation imaging was associated with electrical activation. This study was designed to determine an optimal setting of activation imaging with 3D-STE in comparison with that of a voltage mapping system and to assess the feasibility of this imaging method., Methods and Results: We enrolled 7 patients who underwent electrical voltage mapping. Regional deformation was measured by area change ratio (ACR) with 3D-STE. Activation imaging data were obtained at 10%, 25%, 50%, and 100% of maximal ACR values as the threshold for onset of regional contraction. Duration of LV electrical intraventricular activation time (IVAT(electrical)) by voltage mapping and mechanical IVAT (IVAT(mechanical)) by activation imaging was defined as the time difference between the first and latest endocardial activation sites. We obtained 21 data sets under various conduction patterns and pacing configurations. The strongest correlation between IVAT(mechanical) and IVAT(electrical) was observed at 25% of maximal ACR values (IVAT(electrical)=0.47 * IVAT(mechanical)+20, R=0.80, P<0.001). Concordance of the first and latest activated segments between activation imaging and voltage mapping was 90.5% at this setting (19 studies)., Conclusions: Activation imaging with 3D-STE may be a feasible noninvasive method of dyssynchrony imaging based on electromechanical coupling.

Background: The long-term effects of catheter ablation (CA) on the left atrium and left atrial appendage (LAA) are unknown in persistent atrial fibrillation (AF). This study investigated left atrial (LA) reverse remodeling and evolution of LA/LAA function after successful CA for persistent AF and identified predictors for maintenance of sinus rhythm (SR) and LA reverse remodeling., Methods and Results: CA was performed in 123 patients with persistent AF. LA volumes, LA strain and LAA wall velocity were assessed both at baseline and at 12 months after ablation. Patients who maintained SR were divided into 2 groups according to whether LA volume decreased by ≥15% at follow-up (responders) or not (non-responders). During a follow-up period of 18±2 months, AF recurred in 45 patients (37%). Of the remaining 78 patients (63%) without recurrent AF, 62 patients (79%) were classified as responders. LA/LAA function significantly improved and the prevalence of spontaneous echo contrast decreased only in responders at follow-up. LA systolic strain and LAA wall velocity were independent predictors of both maintenance of SR (odds ratio [OR], 2.57; P=0.003; OR, 3.02; P=0.002, respectively) and LA reverse remodeling (OR, 4.44; P=0.007; OR, 3.52; P=0.01, respectively)., Conclusions: Successful CA is associated with LA reverse remodeling and LA/LAA functional recovery in patients with persistent AF. LA systolic strain and LAA wall velocity at baseline predicted both maintenance of SR and LA reverse remodeling.

Background: Hyperthyroidism is usually regarded as a reversible cause of atrial fibrillation (AF); however, one-third of patients remain in AF despite euthyroid restoration. We hypothesized that a significant number of AF patients with hyperthyroidism (Hyperthyroid-AF) as well as those without (Non-thyroid-AF) would benefit from catheter ablation of AF (AF ablation). This study aimed to clarify the prevalence of hyperthyroidism in candidates for AF ablation and to compare the long-term outcome of AF ablation between the Hyperthyroid-AF and Non-thyroid-AF groups., Methods and Results: This study enrolled 337 consecutive patients with AF who underwent a first AF ablation that mainly involved extensive encircling pulmonary vein isolation. Sixteen (4.7%) patients had hyperthyroidism; the remaining 321 (95.3%) did not. In the Hyperthyroid-AF patients, a euthyroid state had been restored for at least 3 months before the ablation. During a mean follow-up period of 4±1 years after ablation, AF recurred in 7 patients (44%) with Hyperthyroid-AF and in 139 patients (43%) with Non-thyroid-AF (P=0.91 by the log-rank test). In the multivariate Cox regression models, the presence of hyperthyroidism was not associated with a higher risk of AF recurrence (hazard ratio, 0.87; 95% confidence interval, 0.40-1.88; P=0.73)., Conclusions: In the AF ablation candidates without structural heart disease, hyperthyroidism was not rare. After euthyroid restoration on pharmacological treatment, hyperthyroidism was not associated with a higher risk of AF recurrence.

Background: Differences in electrical properties between left and right atria (LA and RA) after pulmonary vein isolation (PVI) for atrial fibrillation (AF) are currently poorly understood. Magnetocardiograms were used to investigate the effect of PVI on bi-atrial magnetic field changes and their relationship to clinical outcomes., Methods and Results: This study included 71 patients undergoing PVI for paroxysmal AF. Magnetocardiograms were recorded at baseline and 1 day, 8 weeks, and 24 weeks after ablation. Peak magnitude of LA and RA segments on P waves was separately compared before and after PVI. During a 16-month post-ablation period, 53 (75%) patients were free from AF recurrences. LA magnetic strength in patients without recurrence persistently decreased for 24 weeks and was significantly lower at 8 weeks than that in patients with recurrence (1.28±0.69 vs. 1.74±0.71 pico-Tesla, P=0.02). RA magnetic strength in patients with recurrence persistently rose for 24 weeks and was significantly higher at 8 weeks than that in patients without recurrence (2.17±0.82 vs. 3.00±1.12 pico-Tesla, P=0.001). Multivariate analysis showed RA magnetic strength at 8 weeks to be the strongest predictor of AF recurrence (odds ratio=3.335; 95% confidence interval=1.181-9.416; P=0.02)., Conclusions: PVI resulted in distinct changes in magnetic strength in both the LA and the RA. A persistent rise in RA magnetic strength might be a robust predictor of AF recurrence after ablation.

Background: The aim of this study was to propose modified tissue Doppler imaging (TDI) parameters derived from the first active wall motion and to assess them for the better prediction of cardiac resynchronization therapy (CRT) responders in comparison with to original TDI parameters., Methods and Results: In 61 patients with CRT, time from QRS onset to peak velocities by TDI (Ts), which were derived from active wall motion identified by longitudinal strain rate (LSR) value, were assessed. Time from QRS onset to the negative peak of LSR (TLSR) was also assessed. Modified standard deviation of Ts in 12 left ventricular (LV) segments (Ts-SD), that of TLSR (TLSR-SD), differences of Ts between septum and lateral wall (Ts-SL), and that of TLSR (TLSR-SL) were calculated. Original Ts-SD and Ts-SL were calculated by previously described methods. Responders were defined as patients with LV end-systolic volume reduction (>15%) at 6 months after CRT: 35 patients (57%) were identified as CRT responders. Area under the receiver-operating characteristics curve (AUC) of modified Ts-SD (0.87) was significantly higher than that of Ts-SD (0.65), Ts-SL (0.62), and TLSR-SL (0.69). AUC of modified Ts-SL was significantly higher than those of Ts-SD, and Ts-SL. AUC of TLSR-SD (0.82) also was significantly higher than that of Ts-SD., Conclusions: Modified TDI dyssynchrony parameters derived from the first active wall motion improve the ability to predict responders to CRT.

Background: Periprocedural anticoagulation using uninterrupted warfarin could reduce the risk of thromboembolic complications of atrial fibrillation (AF) ablation. Few studies, however, have evaluated the efficacy and safety of periprocedural dabigatran in AF ablation., Methods and Results:  A total of 211 consecutive patients who underwent AF ablation, including 110 patients who received 110mg dabigatran twice daily (group D) and 101 patients who received dose-adjusted warfarin (international normalized ratio, 2.0-3.0; group W), were evaluated. Dabigatran was discontinued on the morning of the procedure, and resumed on the next morning. Warfarin was continued throughout the procedure. During the procedure, heparin infusion was maintained to achieve an activated clotting time of >300s. Postprocedural cerebral magnetic resonance imaging (MRI) was performed in 60 patients (group D, n=31; group W, n=29). No periprocedural deaths or symptomatic thromboembolic complications were observed in either group. MRI indicated a silent cerebral infarction in 1 patient in each group. Five patients in group D and 11 in group W had minor bleeding (P=0.12). Cardiac tamponade occurred in 2 patients in group W, but in none in group D. Total bleeding complications occurred less frequently in group D (4.5%) than in group W (12.9%; P<0.05)., Conclusions:  Dabigatran at a dose of 110mg twice daily was safe for AF ablation in patients with a relatively low risk of thromboemboli, suggesting that it may become an alternative to warfarin in those patients.

The aortic root is at the center of the heart. Each of the aortic sinuses of Valsalva, positioned at the base of the aortic root, is in contact with the atrial myocardium and/or ventricular myocardium at their bases, which enables mapping and ablating of some ventricular arrhythmias with an outflow tract origin and supraventricular tachycardias (ie, atrial tachycardia, accessory pathways) from the aortic sinuses of Valsalva. These arrhythmias have characteristic electrocardiographic findings associated with their origins, and almost all are difficult to ablate from an atrial or ventricular endocardial site. Site-specific and potential complications, such as a coronary artery occlusion or atrioventricular block, can occur with catheter ablation at the aortic sinuses of Valsalva. Therefore, accurate diagnosis and proper ablation at the aortic sinuses of Valsalva are required for a cure. This review describes the anatomic features of the aortic sinuses of Valsalva and focuses on the diagnosis and radiofrequency catheter ablation of arrhythmias that can be ablated from this site. (Circ J 2012; 76: 791-800).

Background: Obstructive sleep apnea (OSA) is often associated with atrial fibrillation (AF), but the impact of radiofrequency catheter ablation (RFCA) for AF on sleep apnea syndrome is unknown., Methods and Results: A total of 25 patients (3 women; 61 ± 6 years) with sleep apnea syndrome who underwent RFCA for drug-refractory, persistent AF were studied. Polysomnography was also performed 1 day before and 1 week after RFCA in all patients. The total number of central or OSA or hypopnea events was analyzed and compared. Among the 25 patients who all predominantly had obstructive apnea, the apnea-hypopnea index (AHI; median, 21, interquartile range [IQR]: 11-38 to median 15, IQR: 7-23; P=0.002) and obstructive type of apnea (median 10, IQR: 6-19 to median 7, IQR: 2-14; P=0.003) decreased after RFCA. In patients in whom sinus rhythm was restored and maintained after RFCA, the AHI decreased after RFCA (median 22, IQR: 15-38 to median 15, IQR: 7-23; P<0.01), but it did not in those who had AF recurrence (median 10, IQR: 9-11 to median 11, IQR: 10-16; P<0.05). There was a significant correlation between the outcome of RFCA and % change in the AHI (rs=0.569, P=0.003)., Conclusions: In patients with sleep apnea syndrome and AF, restoring sinus rhythm by RFCA was significantly associated with a decrease in AHI (Clinical Trial Registration: Trial number, UMIN000005538).

Background: Cardiac resynchronization therapy defibrillator (CRT-D) devices are now capable of monitoring changes in intrathoracic impedance. Intrathoracic impedance monitoring resulting in a fluid index threshold crossing has been proven to predict heart failure (HF) exacerbations. We retrospectively investigated the relationship between changes in intrathoracic impedance and the occurrence of arrhythmic events., Methods and Results: From 282 patients with New York Heart Association class III or IV HF who were implanted with a CRT-D device with a fluid index feature based on intrathoracic impedance monitoring capabilities, arrhythmic events were retrospectively analyzed in terms of the threshold crossings. The patients were divided into 2 groups: those with fluid index threshold crossings and those without threshold crossings. A total of 4,725 tachyarrhythmic events were reported in 129 patients (46%), and there were 221 fluid index crossing events in 145 patients (51%) during 10.0 ± 3.2 months. Tachyarrhythmic events were more frequently recorded in patients with threshold crossing events than in those who did not experience a threshold crossing (3,241 vs. 1,484 events, P<0.0001). Ventricular tachyarrhythmic events mainly occurred within the first 30 days after the threshold crossing event; however, a similar trend was not observed for the atrial tachyarrhythmic events., Conclusions: Intrathoracic impedance monitoring may predict arrhythmic events, especially ventricular arrhythmias, in patients with HF and provides an additional management tool.

Background: The prevalence, gender- and age-related differences, ablation success rate and inter-relationship between the origins of the idiopathic ventricular arrhythmias (I-VA) have not been clarified., Methods and Results: A total of 625 consecutive patients with symptomatic, drug resistant I-VA (315 males and 310 females; mean age, 54 ± 17 years; 218 ventricular tachycardias, 407 premature ventricular contractions) who underwent catheter ablation were studied. The patients were divided into 5 groups based on the VA origin: (1) outflow tract (OT)-VA, consisting of right ventricular (RV) OT-VA and left ventricular (LV) OT-VA; (2) inflow tract (IT)-VA, consisting of tricuspid annulus (TA)-free wall (FW)-VA, IT-septum-VA, and mitral (MA)-FW-VA; (3) LV-inferoseptum-VA; (4) LV-other-VA; and (5) RV-other-VA. RVOT-VA in women were 1.5 times more frequent than in men, while LVOT-VA were more frequent in men. The prevalence of LVOT origin I-VA increased with age compared to that for the RVOT. The mean age of MA-FW-VA patients (62 ± 14 years) was higher than that of TA-FW-VA patients (51 ± 18 years; P = 0.03). The ablation success rate for RVOT-VA (88%) was higher than that for LVOT-VA (58%; P<0.0001). A multivariate analysis revealed that the patient age was one of the valuable predictors of a successful ablation (odds ratio=0.97; 95% confidence interval: 0.95-0.99; P=0.007)., Conclusions: Distinct gender and age differences were found in the incidence of I-VA according to their site of origin.

Background: Inflammatory responses following atrial fibrillation (AF) ablation may aggravate arrhythmogenic activity and cause an early recurrence of AF (ERAF)., Methods and Results: In 56 patients who underwent circumferential pulmonary vein ablation (CPVA) for paroxysmal AF, cardiovascular magnetic resonance imaging (CMRI) was evaluated in 5 subdivided left atrial (LA) regions before the CPVA and at 1 day and 1 month after. At a mean of 7+/-10 days after the CPVA, 23 patients (41%) developed 1 or more episodes of AF (ERAF group), while 33 patients (59%) remained free from AF during the first month of follow up (no-ERAF group). LA wall thickness increased 1 day after the CPVA in both groups, as demonstrated by high T2-weighted signal. The LA roof thickness and its increase, however, were greater in the ERAF group than in the no-ERAF group (P<0.05). Regions of delayed enhancement (DE) were also frequently detected in both groups, but the total number of DE regions did not differ between the 2 groups. The thickening of the LA wall associated with a high T2-weighted signal resolved within 1 month. No significant difference between the 2 groups was found in any of the CMRI parameters before or 1 month after CPVA., Conclusions: Thickening of the LA roof shortly after CPVA may predict an ERAF.

Background: Transesophageal echocardiography (TEE) is useful for detecting left atrial (LA) thrombus prior to percutaneous LA catheter ablation in patients with atrial fibrillation (AF). This study was designed to evaluate clinical predictors of LA thrombus and determine indications for TEE screening prior to LA ablation., Methods and Results: The study consisted of 446 patients with drug-resistant AF who were scheduled to undergo initial LA ablation (age 59+/-11 years, 312 males, 136 persistent AF). TEE was performed in all cases within 24 h before ablation. We assessed clinical parameters including CHADS(2) score and echocardiographic parameters. LA thrombus was detected in 13 cases (2.9%) prior to LA ablation (67+/-8 years, 10 males, 12 persistent AF). In multiple logistic regression analysis, advanced age (odds ratio (OR) 1.1, 95% confidence interval (CI) 1.0-1.2; P<0.05), persistent AF (OR 38.1, 95%CI 1.4-988; P<0.05) and structural heart diseases (OR 29.8, 95%CI 2.8-383; P<0.01) were independent positive predictors of LA thrombus prior to ablation, while CHADS(2) score and LA volume were not significant predictors. None of the 136 patients with paroxysmal lone AF whose age was below 60 years had LA thrombus prior to ablation., Conclusions: It might be reasonable to omit TEE as a screening examination for LA thrombus prior to LA ablation in younger paroxysmal lone AF patients.

Background: Cholesterol crystal embolism (CCE) is a serious complication of vascular procedures and based on the clinical features of patients with CCE, the aim of the present study was to establish screening criteria for aortic complex plaques (ACP) at high-risk of CCE., Methods and Results: For the first study, 10 patients diagnosed as having CCE were recruited. They had prior multiple atherosclerotic disease and a high proportion of complex plaques of the carotid artery and aorta. Elevated levels of high-sensitivity C-reactive protein (hs-CRP), eosinophilia, and renal insufficiency were already recognized before CCE diagnosis. The second study prospectively enrolled 102 patients. ACP is related to CCE and predictive criteria of ACP were established. Among 19 patients with ACP, 2 presented with CCE. Multivariate analysis revealed carotid complex plaque, eosinophilia and multiple atherosclerotic risk factors as independent predictors of ACP. The criteria including these factors (multiple atherosclerotic risk factors, carotid complex plaque, hs-CRP > or =0.2 mg/dl, eGFR < or =60 ml . min(-1) . 1.73 m(-2), eosinophil count > or =400 /microl) could detect patients with ACP with 95% sensitivity, 94% specificity, and 79% positive predictive value., Conclusions: Multiple atherosclerotic risk factors, elevated hs-CRP, renal insufficiency, eosinophilia before CCE diagnosis and carotid complex plaques were features of patients with CCE. Diagnostic criteria including these characteristics effectively predict ACP patients at high-risk of CCE. (Circ J 2010; 74: 51 - 58).

Pulmonary embolism (PE) is a fatal disease that is very rare in young people. A 21-year-old man developed PE because of a retroperitoneal tumor. The inferior vena cava (IVC) was obstructed by the tumor, and thrombus existed in the right common iliac vein. Thrombolysis and heparinization improved his symptoms prior to urgent tumor resection. A temporary IVC filter was inserted the day before the operation, but 8 h later fatal massive PE occurred. At autopsy, the retroperitoneal tumor was revealed as a metastatic choriocarcinoma. Prophylactic use of a temporary IVC filter might have paradoxically induced recurrence of massive PE in this case.

Background: Some supraventricular tachycardias could be ablated from the non-coronary sinus of Valsalva (NSV). However, the characteristics of the NSV electrograms have not been clarified., Methods and Results: A quantitative analysis of the NSV electrograms was performed in 5 patients with tachycardias arising from near the atrioventricular node (AVN) and the His-bundle region, and in 20 control subjects. In another 7 control subjects, the NSV electrograms were compared with those recorded at the left and right sinus of Valsalva (LSV and RSV). The NSV electrograms during sinus rhythm had a larger atrial amplitude than ventricular amplitude, and the ratio of the atrial amplitude to the ventricular amplitude was usually >1, which was apparently different from the LSV and RSV electrograms. A tiny but distinct His-bundle deflection was sometimes recorded at the NSV during sinus rhythm while it was not during the tachycardia. The distance to the His-bundle region in the anteroseptal right atrium was shorter from the NSV than from the RSV or LSV., Conclusions: The precise identification of the catheter position at the NSV is possible using the characteristics of the electrograms. Much attention should be paid during ablation to the NSV because of its vicinity to the AVN and His-bundle region.

In 1982, a 49-year-old Japanese woman had been referred to our hospital for further investigation of her hypercholesterolemia. She was diagnosed as heterozygous familial hypercholesterolemia, because of Achilles tendon xanthoma and a family history of primary hypercholesterolemia. Three years later, she had chest pain on effort and angina pectoris was diagnosed by coronary angiography. At that time, she underwent coronary artery bypass grafting surgery with 2 saphenous vein grafts (SVG). Because more aggressive cholesterol-lowering therapy was needed for secondary prevention of coronary artery disease (CAD), weekly low-density lipoprotein (LDL) apheresis was started postoperatively, combined with drug therapy. Since 1986, her serum total cholesterol levels before and after LDL apheresis remained approximately 200 mg/dl and 90 mg/dl, respectively. Although her coronary sclerosis, including the SVG, did not progress appreciably for a period of 20 years, stenotic changes of the aortic valve developed rapidly at age 70, leading to aortic valve replacement surgery in 2005 at age 72. These findings suggest that careful attention to the progression of aortic valve stenosis is needed for extreme hypercholesterolemic patients even under optimal cholesterol-lowering therapy for the secondary prevention of CAD.

Background: The aim of this study was to retrospectively investigate the long-term effect of cardiac resynchronization therapy (CRT) and to clarify the useful predictors of clinical outcome. Methods and Results The study group comprised 43 patients with advanced heart failure who underwent CRT (10 females; 66+/-10 years): 23 were in sinus rhythm (SR group) and 20 had chronic atrial fibrillation (AF group). The clinical parameters and echocardiographic data were evaluated before and after CRT. There were no significant differences in the clinical parameters, echocardiographic data at baseline or frequency of responders between the 2 groups. In both groups, the clinical characteristics at baseline did not differ between the responders and non-responders. A prompt rise in systolic blood pressure (SBP) just after CRT was observed more often in responders than in non-responders, and SBP rise > or =5 mmHg was the only significant independent predictor of a CRT responder (P=0.0033). Furthermore, there was a significant difference in the event-free survival between patients with and without SBP rise > or =5 mmHg, demonstrated by Kaplan-Meier method, at 2 years of follow-up (P=0.045). Conclusion A prompt BP rise just after CRT may predict short- and long-term clinical improvement in CRT recipients.

A 63-year-old woman was admitted to hospital with the chief complaint of new onset chest discomfort and pretibial pitting edema. Transthoracic echocardiography revealed a large invasive tumor on the heart protruding into the right atrium and right ventricle, which obstructed the outflow tract. She underwent transvenous 9Fr, 9-MHz ultra intracardiac echocardiography (ICE) (EP Technologies, Boston Scientific Corporation, San Jose, CA, USA) guided biopsy, and a diagnosis of malignant lymphoma was established from the specimen obtained. ICE-guided cardiac tumor biopsy may be one of the most useful strategies for diagnosis of cardiac tumors.

Background: The indications and efficacy of cardiac resynchronization therapy (CRT) have not been sufficiently clarified in patients with right bundle branch block (RBBB)., Methods and Results: This study included 55 patients with normal QRS morphology and duration (Control-Gr) and 49 patients with complete RBBB (CRBBB-Gr). Using tissue Doppler imaging, the time difference (TD) between the electromechanical delay of the septal wall, left ventricular (LV) lateral wall, and right ventricular free wall were measured. Using tissue tracking imaging, the coefficient of the time variation from the beginning of the QRS to the peak displacement time of 6 regions of the LV (CV-PMDLV) was calculated. The TD between the septal wall and that of the LV lateral wall (TDSEPT-LAT) did not differ between the Control-Gr and RBBB-Gr. However, a significant difference was found in the TDSEPT-LAT between the CRBBB patients with LV systolic dysfunction (ejection fraction (EF) < or =50%) and those with normal LV function (EF >50%; p<0.001). The CV-PMDLV was greater in the CRBBB patients with LV systolic dysfunction than in those with a normal LV function (p<0.05). The RBBB-Gr patients with LV dysfunction and a great TDSEPT-LAT, improved clinically after the CRT., Conclusions: The presence of RBBB and LV dysfunction may indicate LV dyssynchrony and a heterogeneous mechanical dysfunction.

A patient underwent radiofrequency (RF) catheter ablation for a drug-refractory ventricular tachycardia, but RF energy application at an endocardial site of the left ventricular outflow tract and at the left sinus of Valsalva could not eliminate the tachycardia. The earliest ventricular activation during the arrhythmia, which preceded the onset of the QRS complex by 32 ms, was found within the great cardiac vein and complete elimination of the tachycardia was finally achieved with RF application at that site.