Collagen triple helix repeat-containing protein 1 is a novel biomarker of right ventricular involvement in pulmonary hypertension.

BACKGROUND: Pulmonary hypertension leads to right ventricular failure, which is a major determinant of prognosis. Circulating biomarkers for right ventricular function are poorly explored in pulmonary hypertension. This study aimed to clarify the significance of collagen triple helix repeat-containing protein 1 (CTHRC1) as a biomarker of right ventricular failure in pulmonary hypertension. METHODS: A monocrotaline-induced pulmonary hypertension rat model was used to evaluate right ventricular CTHRC1 expression and its relationship with fibrosis. Next, human plasma CTHRC1 levels were measured in controls (n = 20), pulmonary arterial hypertension (n = 46), and chronic thromboembolic pulmonary hypertension (CTEPH) patients (n = 64) before the first and after the final balloon pulmonary angioplasty. RESULTS: CTHRC1 expression was higher in the right ventricles of rats with monocrotaline-induced pulmonary hypertension than in those of controls. CTHRC1 was co-localized with vimentin and associated with fibrosis in the right ventricles. Plasma CTHRC1 levels were higher in human pulmonary arterial hypertension (P = 0.006) and CTEPH patients (P = 0.011) than in controls. Plasma CTHRC levels were correlated with B-type natriuretic peptide (R = 0.355, P < 0.001), tricuspid lateral annular peak systolic velocity (R = -0.213, P = 0.029), and right ventricular fractional area change (R = -0.225, P = 0.017). Finally, plasma CTHRC1 levels were decreased after the final balloon pulmonary angioplasty (P < 0.001) in CTEPH. CONCLUSIONS: CTHRC1 can be a circulating biomarker associated with right ventricular function and fibrosis in pulmonary hypertension and might reflect the therapeutic efficacy of balloon pulmonary angioplasty in CTEPH.

Predictive Value of Aortic Valve Calcium Volume Measured by Computed Tomography for Paravalvular Leakage After Transcatheter Aortic Valve Implantation.

Paravalvular leakage (PVL) is a complication of transcatheter aortic valve implantation (TAVI) for aortic stenosis, leading to an adverse prognosis. We investigated whether aortic valve calcium volume (Ca-Vol) measured by preoperative cardiac computed tomography had a predictive value for PVL after TAVI using a third-generation self-expandable valve.We retrospectively analyzed 59 consecutive patients who underwent TAVI using a third-generation self-expandable valve. We measured Ca-Vol in the aortic valve and each cusp (non-coronary cusp [NCC], right-coronary cusp [RCC], and left-coronary cusp [LCC]). We divided the patients into 2 groups: a PVL group (32.2%) and a non-PVL group (67.8%). Total Ca-Vol was significantly higher in the PVL group than in the non-PVL group (P < 0.001). Ca-Vol in each cusp was also significantly higher in the PVL group ([NCC] P < 0.001, [RCC] P = 0.001, [LCC] P < 0.001). Univariate logistic regression analysis for PVL indicated that the total and per-cusp Ca-Vols were predictors for PVL (total, odds ratio [OR] 4.0, P < 0.001; NCC, OR 12.5, P = 0.002; RCC, OR 16.0, P = 0.008; LCC, OR 44.5, P < 0.001).Receiver operating characteristic curve analysis of Ca-Vol for predicting PVL revealed the optimal cut-off values of Ca-Vol were 2.4 cm3 for the total, 0.74 cm3 for NCC, 0.73 cm3 for RCC, and 0.56 cm3 for LCC (area under the curve, 0.85, 0.79, 0.76, and 0.83, respectively).Preoperative total, NCC, RCC, and LCC calcium volumes were significant predictors for PVL after TAVI using third-generation self-expandable valves.

Characteristics of right pulmonary vein with an epicardial connection needing additional carina ablation for isolation.

Background: This study thought to elucidate the anatomical features that can predict an epicardial connection (EC) between the right pulmonary vein (RPV) and right atrium. Methods: We retrospectively analyzed 251 consecutive patients undergoing initial radiofrequency pulmonary vein isolation. We defined EC as present when RPV could not be isolated with circumferential ablation and additional ablation for the conduction gap if needed, and RPV isolation could be achieved by ablation for the earliest activation site >10 mm inside the initial ablation line. Using computed tomography data, we evaluated the RPV bifurcation angle, and the area occupation ratio of the carina region to the RPV antrum (ARC) for predicting EC. In subjects with EC undergoing RPV activation mapping after circumferential ablation, the correlation between conduction delay and bipolar/unipolar potential voltage in the carina region was investigated. Results: There were ECs in 45 out of 251 patients (17.9%). The RPV bifurcation angle (47.7° vs. 38.8°, p < .001) and ARC (37.2% vs. 29.7%, p < .001) were significantly greater in the EC (+) group. Multivariate logistic regression analysis revealed that RPV bifurcation angle (odds ratio [OR]: 1.994, p = .002) and ARC (OR: 3.490, p = .013) were independent predictors of EC. In nine patients with EC undergoing carina region mapping, the unipolar potential voltage was correlated with conduction delay in RPV with EC (R = -0.401, p < .001). Conclusion: Anatomical features suggesting a wider RPV carina region could predict the presence of EC, and potential with high voltage could be helpful for detecting EC connection sites.

Perioperative immunosuppressive therapy and coronary ostial angioplasty for unstable angina with Takayasu arteritis.

A young female patient with Takayasu arteritis presented with unstable angina due to bilateral coronary artery involvement. Steroid pulse therapy and subsequent prednisolone administration were started, but early coronary artery bypass grafting was required because of the multiple angina attacks at rest, with a prednisolone dose of 22.5 mg (0.45 mg/kg/day). Since the left internal thoracic artery which was grafted to the left anterior descending artery resulted in graft failure a few days after the surgery, the immunosuppressive therapy was intensified with the addition of tocilizumab and methotrexate. After controlling the disease activity, coronary ostial angioplasty using external iliac artery grafts was successfully performed, with a prednisolone dose of 15 mg (0.3 mg/kg/day). Ten months after the operation, the patient has been free from chest pain. The present case demonstrated the importance of adequate preoperative immunosuppressive therapy, even when early surgical intervention is required. Learning objective: There are no established treatment regimens for immunosuppressive management in cases of Takayasu arteritis (TAK) requiring immediate surgical intervention. Even when early surgery is required, it is important to reduce disease activity with appropriate preoperative immunosuppressive therapy using steroids in addition to biological agents, such as tocilizumab. Coronary ostial angioplasty is the effective surgical revascularization technique for TAK with coronary artery involvement.

Unipolar-voltage-based evaluation of left atrial tissue properties and ablation outcome in patients with atrial fibrillation.

AIMS: The relationship between local unipolar voltage (UV) in the pulmonary vein (PV)-ostia and left atrial wall thickness (LAWT) and the utility of these parameters as indices of outcome after atrial fibrillation (AF) ablation remain unclear. METHODS AND RESULTS: Two-hundred seventy-two AF patients who underwent AF ablation were enrolled. Unipolar voltage of PV-ostia was measured using a CARTO system, and LAWT was measured using computed tomography. The primary endpoint was atrial tachyarrhythmia (ATA) recurrence including AF. The ATA recurrence was documented in 74 patients (ATA-Rec group). The UV and LAWT of the bilateral superior PV roof to posterior and around the right-inferior PV in the ATA-Rec group were significantly greater than in patients without ATA recurrence (ATA-Free group) (P < 0.001). The UV had a strong positive correlation with LAWT (R2 = 0.446, P < 0.001). The UV 2.7 mV and the corresponding LAWT 1.6 mm were determined as the cut-off values for ATA recurrence (P < 0.001, respectively). Multisite LA high UV (HUV, ≥4 areas of >2.7 mV) or multisite LA wall thickening (≥5 areas of >1.6 mm), defined as LA hypertrophy (LAH), was related to higher ATA recurrence. Among 92 LAH patients, 66 had HUV (LAH-HUV) and the remaining 26 had low UV (LAH-LUV), characterized by history of non-paroxysmal AF and heart failure, reduced LV ejection fraction, or enlarged LA. In addition, LAH-LUV showed the worst ablation outcome, followed by LAH-HUV and No LAH (log-rank P < 0.001). CONCLUSION: Combining UV and LAWT enables us to stratify recurrence risk and suggest a tailored ablation strategy according to LA tissue properties.

Utility of short-time electrocardiogram to assess risk for atrial arrhythmia recurrence: Impact of atrial premature beat occurrence 1 day after pulmonary vein isolation for atrial fibrillation.

INTRODUCTION: Atrial premature beats (APBs) are the trigger for atrial fibrillation (AF). We sought to investigate the clinical significance of APB occurrence 1 day after pulmonary vein isolation (PVI) for AF using a short-time electrocardiogram. METHODS: A total of 206 patients undergoing PVI for paroxysmal AF were included. Electrocardiogram recording for 100 consecutive beats was performed 1 day after PVI. The patients were divided into two groups: those with reproducible APBs (≥1 beat) during reassessment (APB group, n = 49) or those without (non-APB group, n = 157). Late recurrence was defined as atrial tachyarrhythmia recurrence 3-12 months after PVI. The impact of APB occurrence on outcomes was investigated. RESULTS: Late recurrence occurred in 19 patients (9.2%). The presence of low-voltage areas, left atrial volume, and recurrence rate were higher in the APB group than in the non-APB group. In the APB group, the patients with recurrence had lower prematurity index (PI, coupling interval of APB/previous cycle length) compared to those without. Receiver-operating characteristic analysis revealed PI (<59.3) to be a predictive factor of recurrence (area under the curve: 0.733). The study subjects were then reclassified into three groups according to the absence of APB occurrence (n = 157), presence thereof with PI ≥ 59.3 (n = 33), and presence with PI < 59.3 (n = 16). The multivariate Cox models revealed that APB with PI < 59.3 was an independent predictor for recurrence (hazard ratio, 8.735; p < 0.001). CONCLUSION: A short-time electrocardiogram enables risk assessment for arrhythmia recurrence, and APB with low PI 1 day after PVI is a powerful predictor.

Prognostic Role of Circulating LTBP-2 in Patients With Dilated Cardiomyopathy: A Novel Biomarker Reflecting Extracellular Matrix LTBP-2 Accumulation.

BACKGROUND: Dilated cardiomyopathy (DCM) is a life-threatening disease related to heart failure. Extracellular matrix proteins have an important role in the pathogenesis of DCM. Latent transforming growth factor beta-binding protein 2 (LTBP-2), a type of extracellular matrix protein, has not been investigated in DCM. METHODS: First, we compared plasma LTBP-2 levels in 131 patients with DCM who underwent endomyocardial biopsy and 44 controls who were matched for age and sex and had no cardiac abnormalities. Next, we performed immunohistochemistry for LTBP-2 on endomyocardial biopsy specimens and followed the DCM patients for ventricular assist device (VAD) implantation, cardiac death, and all-cause death. RESULTS: Patients with DCM had elevated plasma LTBP-2 levels compared with controls (P < 0.001). Plasma LTBP-2 levels were positively correlated with LTBP-2-positive fraction in the myocardium from the biopsy specimen. When patients with DCM were divided into 2 groups according to LTBP-2 levels, Kaplan-Meier analysis demonstrated that patients with high plasma LTBP-2 were associated with increased incidences of cardiac death/VAD and all-cause death/VAD. In addition, patients with high myocardial LTBP-2-positive fractions were associated with increased incidences of these adverse outcomes. Multivariable Cox proportional hazard analysis showed that plasma LTBP-2 and myocardial LTBP-2-positive fraction were independently associated with adverse outcomes. CONCLUSIONS: Circulating LTBP-2 can serve as a biomarker to predict adverse outcomes, reflecting extracellular matrix LTBP-2 accumulation in the myocardium in DCM.

Left atrial epicardial adipose tissue exacerbates electrical conduction disturbance in normal-weight patients undergoing pulmonary vein isolation for atrial fibrillation.

INTRODUCTION: Epicardial adipose tissue (EAT) exacerbates both electrical and structural remodeling in obese atrial fibrillation (AF) patients, but the impacts of EAT on atrial arrhythmogenicity remain unclear in normal-weight AF patients. Therefore, we sought to investigate this issue using electroanatomic mapping. METHODS AND RESULTS: We enrolled drug-refractory 105 paroxysmal AF patients in the normal body mass index range (18.5-24.9 kg/m2 ), who had undergone electroanatomic mapping after pulmonary vein isolation (PVI). One day before PVI, we assessed P-wave duration in a 12-lead electrocardiogram and left atrial (LA)-EAT volumes using contrast-enhanced computed tomography. The patients were divided into two groups based on the median LA-EAT volume (16.0 ml); the high LA-EAT group (≥16.0 ml, n = 53) and low LA-EAT group (<16.0 ml, n = 52). We compared P-wave duration, LA conduction velocity and bipolar voltage, the presence of low-voltage zone (<0.5 mV), and LA volume index on echocardiography between the two groups. The LA bipolar voltage, low-voltage zone, and LA volume index were not different between the high and low LA-EAT groups. However, P-wave duration was significantly longer in the high group than in the low group (p < .001). Additionally, the LA conduction velocity was significantly more depressed in the high group than in the low group (p < .001). Multivariate linear regression analysis revealed that LA-EAT volume was correlated with P-wave duration (ß = .367, p < .001) and conduction velocity (ß = -.566, p < .001), respectively. CONCLUSIONS: Increased LA-EAT volumes were associated with electrical conduction disturbance after PVI in normal-weight patients with AF. P-wave duration may be a clinically useful predictor of LA-EAT.

Utility of a novel wearable electrode embedded in an undershirt for electrocardiogram monitoring and detection of arrhythmias.

BACKGROUND: A 12-lead electrocardiogram (ECG) and Holter ECG have been established as gold standards for detection of arrhythmias. Recently, wearable ECG monitoring devices have been available. Our purpose of the present study was to investigate whether a novel wearable electrode embedded in an undershirt is useful for ECG monitoring and detection of arrhythmias. METHODS: We studied 31 consecutive hospitalized patients who underwent catheter ablation of tachyarrhythmias. Patients equipped a wearable electrode and a lead CM5 of Holter ECG simultaneously, and total heart beats, maximum heart rate (HR), mean HR, minimum HR, detections of arrhythmias, such as atrial fibrillation, non-sustained ventricular tachycardia, and premature ventricular contractions (Lown's grade >II), were compared between the two methods using a Holter ECG analysis software. RESULTS: Median recording time of ECG by wearable electrodes was 12.6 hours. Strong correlations between the two methods were observed in total heart beats (R = 0.999, P <0.001), maximum HR (R = 0.997, P <0.001), mean HR (R = 0.999, P <0.001), minimum HR (R = 0.989, P <0.001) and QRS duration (R = 0.900, P <0.001). Bland-Altman analysis showed excellent concordance between each parameter measured by two methods. In addition, the detection of atrial fibrillation (nine events), non-sustained ventricular tachycardia (two events), and premature ventricular contractions of Lown's grade >II (five events) were concordant in two methods. In addition, there were no significant difference in parameters of time-domain and frequency-domain analyses of heart rate variability between the two methods. CONCLUSIONS: The usefulness of a novel electrode embedded in an undershirt is equivalent to that of a Holter ECG in monitoring the ECG and detection of arrythmias.

Impaired brain activity in patients with persistent atrial fibrillation assessed by near-infrared spectroscopy and its changes after catheter ablation.

Although the prevalence of cognitive impairment and depression is higher in patients with atrial fibrillation (AF) than in the general population, the mechanism has not been fully examined and impact of catheter ablation (CA) of AF also remains unclear. Recently, the development of near-infrared spectroscopy (NIRS) has enabled noninvasive measurements of regional cerebral blood volume and brain activity, in terms of cerebral oxyhemoglobin in the cerebral cortex. We assessed brain activities by NIRS, depressive symptoms by the Center for Epidemiologic Studies Depression Scale (CES-D) and cognitive function by Mini-Mental State Examination (MMSE). We then compared the results between AF patients (paroxysmal AF n = 18 and persistent AF n = 14) and control subjects (n = 29). Next, we also followed up persistent AF patients who kept sinus rhythm at 3 months after CA (n = 8) and measured their brain activities using NIRS, CES-D and MMSE after CA to investigate the associations of changes in brain activities with changes in both CES-D and MMSE. Our results showed that (1) frontal and temporal brain activities were lower in patients with persistent AF than both in control subjects and paroxysmal AF patients (P < 0.01), (2) frontal and temporal brain activities were improved in more than half of the persistent AF patients who kept sinus rhythm at 3 months after CA, especially in those who presented impaired brain activity before CA, and (3) improvement of frontal brain activity was associated with improvement of CES-D (R = - 0.793, P = 0.019), whereas improvement of temporal brain activity was associated with improvement of MMSE (R = 0.749, P = 0.033). NIRS measurement showed reduced frontal and temporal brain activities in the persistent AF patients, CA improved frontal and temporal brain activities in some of these patients, and associated with improvement of depressive state and/or improvement of cognitive function.

Renal Venous Stasis Index Reflects Renal Congestion and Predicts Adverse Outcomes in Patients With Heart Failure.

Background: It has been recently reported that the renal venous stasis index (RVSI) assessed by renal Doppler ultrasonography provides information to stratify pulmonary hypertension that can lead to right-sided heart failure (HF). However, the clinical significance of RVSI in HF patients has not been sufficiently examined. We aimed to examine the associations of RVSI with parameters of cardiac function and right heart catheterization (RHC), as well as with prognosis, in patients with HF. Methods: We performed renal Doppler ultrasonography, echocardiography and RHC in hospitalized patients with HF (n = 388). RVSI was calculated as follows: RVSI = (cardiac cycle time-venous flow time)/cardiac cycle time. The patients were classified to three groups based on RVSI: control group (RVSI = 0, n = 260, 67%), low RVSI group (0 < RVSI ≤ 0.21, n = 63, 16%) and high RVSI group (RVSI > 0.21, n = 65, 17%). We examined associations of RVSI with parameters of cardiac function and RHC, and followed up for cardiac events defined as cardiac death or worsening HF. Results: There were significant correlations of RVSI with mean right atrial pressure (mRAP; R = 0.253, P < 0.001), right atrial area (R = 0.327, P < 0.001) and inferior vena cava diameter (R = 0.327, P < 0.001), but not with cardiac index (R = -0.019, P = 0.769). During the follow-up period (median 412 days), cardiac events occurred in 60 patients. In the Kaplan-Meier analysis, the cumulative cardiac event rate increased with increasing RVSI (log-rank, P = 0.001). In the multivariate Cox proportional hazard analysis, the cardiac event rate was independently associated with RVSI (high RVSI group vs. control group: hazard ratio, 1.908; 95% confidence interval, 1.046-3.479, P = 0.035). Conclusion: RVSI assessed by renal Doppler ultrasonography reflects right-sided overload and is associated with adverse prognosis in HF patients.

Procedural characteristics of pulmonary vein isolation with high-power short-duration setting compared to conventional setting.

PURPOSE: The purpose of this study was to investigate the safety and efficacy of high-power short-duration (HP-SD) ablation compared to conventional ablation in patients with atrial fibrillation (AF). METHODS: We enrolled consecutive 158 drug-refractory symptomatic AF patients (119 males, mean age 63 ± 10 years) who had undergone first radiofrequency pulmonary vein isolation (PVI). PVI was performed using the conventional setting (20-35 W) in 73 patients (Conventional group) and using the HP-SD setting (45-50 W) in 85 patients (HP-SD group). The rate of first pass isolation, remaining gaps after circumferential ablation, dormant conduction, and the radiofrequency application time in each pulmonary vein (PV) were compared between the groups. RESULTS: The first pass isolation ratio was significantly higher in the HP-SD group than in the Conventional group (81% vs. 65%, P = 0.027) in the right PV, but did not differ in the left PV. The remaining gaps were fewer in the right superior PV (4% vs. 21%, P = 0.001) and left inferior PV (1% vs. 8%, P = 0.032) areas, and the radiofrequency application time in each PV was shorter (right PV, 12.0 ± 8.9 min vs. 34.0 ± 31.7 min, P < 0.001; left PV, 10.6 ± 3.6 min vs. 25.7 ± 22.3 min, P < 0.001) in the HP-SD group than in the Conventional group. CONCLUSION: The use of the HP-SD setting might contribute to improve the first pass isolation rate and to shorten the radiofrequency application time in each PV.

Predictive impacts of chronic kidney disease and cardiac sympathetic nervous activity on lethal arrhythmic events in chronic heart failure.

BACKGROUND: The clinical implications of chronic kidney disease (CKD) and cardiac sympathetic nervous activity (CSNA) regarding lethal arrhythmic events have not yet been fully elucidated in patients with chronic heart failure (CHF). We hypothesized that the combination of CKD and abnormal CSNA, assessed by 123 I-metaiodobenzylguanidine (123 I-MIBG) scintigraphy, may provide useful prognostic information for lethal arrhythmic events. METHODS: We studied 165 consecutive hospitalized CHF patients without dialysis. Cardiac 123 I-MIBG scintigraphy was performed in a clinically stable condition, and abnormal CSNA was defined as a late heart-to-mediastinum ratio of <1.6. CKD was defined as an estimated glomerular filtration rate of <60 ml/min/1.73 m2 . We then investigated the incidence of lethal arrhythmic events (sustained ventricular tachyarrhythmia, appropriate implantable cardioverter-defibrillator therapy, or sudden cardiac death). RESULTS: During a median follow-up of 5.3 years, lethal arrhythmic events were observed in 40 patients (24.2%). The patients were divided into four groups according to the presence of CKD and CSNA abnormality: non-CKD/normal CSNA (n = 52), CKD/normal CSNA (n = 39), non-CKD/abnormal CSNA (n = 33), and CKD/abnormal CSNA (n = 41). Kaplan-Meier analysis showed that CKD/abnormal CSNA had the highest event rate (log-rank p = .004). Additionally, the Cox proportional hazard analysis revealed that CKD/abnormal CSNA was a predictor for lethal arrhythmic events compared with non-CKD/normal CSNA (hazard ratio, 5.368, p = .001). However, the other two groups did not show significant differences compared with the non-CKD/normal CSNA group. CONCLUSIONS: The combination of CKD and abnormal CSNA, assessed by 123 I-MIBG scintigraphy, had a high predictive value for lethal arrhythmic events in patients with CHF.

Influence of power setting on superior vena cava potential during right pulmonary vein isolation.

PURPOSE: High-power short-duration (HP-SD) ablation could reduce collateral tissue damage by shortening the conductive heating phase. However, it is difficult to evaluate the transmural effect of ablation lesions during pulmonary vein isolation (PVI) procedures. The present study aimed to evaluate the change in superior vena cava (SVC) potential delay as a surrogate marker of collateral tissue damage during right PVI, which is adjacent to SVC. METHODS: Out of 250 consecutive patients who underwent PVI, 86 patients in whom SVC potential during sinus rhythm was recorded both before and after right PVI were analyzed. In 46 of the patients, an HP-SD setting of 45-50 W was used (HP-SD group). In the remaining 40 patients, a conventional power setting of 20-30 W was used (conventional group). We compared the change in SVC potential delay after right PVI, radiofrequency energy, and mean contact force in the anterior-superior right PVI line, which was close to the posterior aspect of SVC, between the two groups. RESULTS: Although the total delivered radiofrequency energy (2,924 J vs. 2,604 J) and the mean contact force (18.5 g vs. 16.0 g) in the SVC overlapping area did not differ, the change in SVC potential delay after right PVI was significantly longer in the conventional group compared to the HP-SD group (5.0 ms vs. 0.0 ms, p < 0.001). CONCLUSIONS: The changes in SVC potential delay after right PVI might be a surrogate marker of collateral tissue damage according to the used energy settings.

Autonomic cardiogastric neural interaction after pulmonary vein isolation in patients with atrial fibrillation.

PURPOSE: Clinical significance of reduced vagal activity following pulmonary vein isolation (PVI) for atrial fibrillation (AF) remains unclear. Periesophageal vagal nerve injury following PVI may be a powerful contributing factor of decreased vagal tone. METHODS: Drug-refractory 51 AF patients (31 males, 64 ± 11 years), who underwent successful PVI, were enrolled. We performed esophagogastroduodenoscopy 2 days after PVI and assessed delayed gastric emptying (DGE). Additionally, the coefficient of variance of R-R interval (CVRR) as a surrogate for vagal tone was measured before PVI, as well as at 1 day and 3 months after PVI. The patients were divided into two groups, patients with DGE and patients without DGE, and changes in CVRR were compared. RESULTS: After PVI, 12 out of 51 patients (23.5%) had DGE. The baseline CVRR did not differ between the patients with (n = 12) and those without (n = 39) DGE (median 3.13%, interquartile range 1.69-5.13 vs. median 3.76%, interquartile range 2.96-5.90, P = 0.297). However, CVRR at 1 day after PVI was significantly lower in the patients with DGE than in those without (median 1.49%, interquartile range 0.90-2.19 vs. median 2.59%, interquartile range 1.58-3.86, P = 0.035), and then CVRR at 3 months became similar between the two groups, suggesting that the two groups had different changes in vagal tone after PVI. The recurrence of AF was similar at 3-6 months after PVI between the two groups. CONCLUSIONS: A significantly decreased CVRR immediately after PVI is a sign of DGE incidence, implying collateral damage to the esophagus.

Electrophysiological properties and involvement of anatomical factors for the prediction of intramural origin in patients with ventricular tachyarrhythmia arising from the left ventricular outflow tract.

PURPOSE: To elucidate the electrophysiological predictors of the intramural origins of left ventricular outflow tract-ventricular tachyarrhythmias (LVOT-VAs), and to clarify the involvement of anatomical factors. METHODS: Twenty-nine successfully ablated LVOT-VAs patients with origins in the aortomitral continuity (AMC) (n = 8), aortic sinus of valsalva (ASV) (n = 9), great cardiac vein (GCV) (n = 5), and intramural myocardium (n = 7) were enrolled. Intramural origins were defined as when effective ablation from AMC and epicardium (ASV and/or GCV) was needed. The local activation time difference (LATD) was calculated as follows: (earliest AMC activation) - (earliest epicardial activation), and was presented as an absolute value. Electrophysiological parameters and anatomical factors predisposing the intramural origins were investigated. RESULTS: LATD of intramural origins was significantly shorter than that of AMC and GCV (4.5 ± 2.6 vs. 12.1 ± 7.4 vs. 17.4 ± 4.7, P < 0.05), respectively. In multivariate logistic regression analysis, LATD was associated with intramural origins (odds ratio: 0.711, confidence interval: 0.514-0.985, P = 0.040). ROC analysis revealed LATD of 7 ms as cut-off value. In computed tomography analysis, some patients who had thick fat tissue below the GCV, and an unusual GCV running pattern might be misdiagnosed as intramural origins. CONCLUSION: LATD ≤ 7 ms was associated with intramural origins, but with some anatomical limitations.

Esophageal thermal injury in catheter ablation of atrial fibrillation.

Pulmonary vein isolation is an established method for the catheter ablation of atrial fibrillation. Esophageal thermal injuries, such as esophageal erosion, ulceration and periesophageal nerve injury leading to gastric hypomotility, are important complications associated with pulmonary vein isolation. In this review article, we describe the mechanisms, characteristics and the predictors of esophageal thermal injury associated with pulmonary vein isolation.

Albumin-Bilirubin Score for Prediction of Outcomes in Heart Failure Patients Treated with Cardiac Resynchronization Therapy.

BACKGROUND: Liver function may be a useful indicator of response to cardiac resynchronization therapy (CRT). We aimed to investigate the clinical significance of albumin-bilirubin (ALBI) score, an assessment tool of liver function, on outcomes in heart failure (HF) patients treated with CRT. METHODS: We studied 180 patients undergoing CRT. The ALBI score, derived from albumin and total bilirubin, and left ventricular ejection fraction (LVEF) were assessed before and 6 months after CRT. The patients were classified according to the ALBI score before CRT; High (>-2.60) or Low (≤-2.60) ALBI groups. The patients were then reclassified based on the ALBI score before and 6 months after CRT; High/High, High/Low, Low/High, and Low/Low ALBI groups. We evaluated the prognostic value of the ALBI score for HF deaths after CRT. RESULTS: During a median follow-up period of 50 months, there were 41 (22.7%) HF deaths. A Cox proportional hazard analysis revealed that high ALBI scores at baseline were not related to HF deaths (hazard ratio, 1.907, p = 0.068). However, High/High ALBI scores, but not High/Low or Low/High ALBI scores, were an independent predictor of HF deaths compared with Low/Low ALBI scores (hazard ratio, 3.449, p = 0.008), implying that consistently high ALBI scores were associated with poor prognosis. The percentage change in LVEF from baseline to 6 months after CRT did not differ among the four groups, suggesting that left ventricular systolic function was not linked with the ALBI score. CONCLUSIONS: ALBI scores before and after CRT are a new indicator of CRT response, and have a predictive value for HF deaths in HF patients.

Blood-Based Epigenetic Markers of FKBP5 Gene Methylation in Patients With Dilated Cardiomyopathy.

Background Blood-based DNA methylation patterns are linked to types of diseases. FKBP prolyl isomerase 5 (FKBP5), a protein cochaperone, is known to be associated with the inflammatory response, but the regulatory mechanisms by leukocyte FKBP5 DNA methylation in patients with dilated cardiomyopathy (DCM) remain unclear. Methods and Results The present study enrolled patients with DCM (n=31) and age-matched and sex-matched control participants (n=43). We assessed FKBP5 CpG (cytosine-phosphate-guanine) methylation of CpG islands at the 5' side as well as putative promoter regions by methylation-specific quantitative polymerase chain reaction using leukocyte DNA isolated from the peripheral blood. FKBP5 CpG methylation levels at the CpG island of the gene body and the promoter regions were significantly decreased in patients with DCM. Leukocyte FKBP5 and IL-1ß (interleukin 1ß) mRNA expression levels were significantly higher in patients with DCM than in controls. The protein expressions of DNMT1 (DNA methyltransferase 1) and DNMT3A (DNA methyltransferase 3A) in leukocytes were significantly reduced in patients with DCM. In vitro methylation assay revealed that FKBP5 promoter activity was inhibited at the methylated conditions in response to immune stimulation, suggesting that the decreased FKBP5 CpG methylation was functionally associated with elevation of FKBP5 mRNA expressions. Histological analysis using a mouse model with pressure overload showed that FKBP5-expressing cells were substantially infiltrated in the myocardial interstitium in the failing hearts, indicating a possible role of FKBP5 expressions of immune cells in the cardiac remodeling. Conclusions Our findings demonstrate a link between specific CpG hypomethylation of leukocyte FKBP5 and DCM. Blood-based epigenetic modification in FKBP5 may be a novel molecular mechanism that contributes to the pathogenesis of DCM.