Real-World Patent Foramen Ovale (PFO) Closure in Japan　- 30-Day Clinical Outcomes From the AmplatzerTM PFO Occluder Japan Post-Marketing Surveillance Study.

BACKGROUND: The AmplatzerTM PFO Occluder was approved for marketing in Japan in May 2019, and the Amplatzer PFO Occluder Japan Post-marketing Surveillance (PFO Japan PMS) study was initiated in December 2019. This analysis presents 30-day clinical outcomes for PFO Japan PMS study patients. METHODS AND RESULTS: PFO Japan PMS is a prospective single-arm non-randomized multicenter clinical study. Eligible patients were indicated for patent foramen ovale (PFO) closure and underwent an implant attempt with the AmplatzerTM PFO Occluder. Technical success was defined as successful delivery and release of the occluder; procedural success was defined as technical success with no serious adverse events (SAEs) within 1 day of the procedure. The primary safety endpoint includes predefined device- and/or procedure-related SAEs through 30 days after the procedure. From December 2019 to July 2021, 500 patients were enrolled across 53 Japanese sites. The mean (±SD) patient age was 52.7±15.4 years, and 29.8% of patients were aged >60 years. Technical and procedural success rates were both high (99.8% and 98.8%, respectively). Further, there was only one primary safety endpoint event (0.2%): an episode of asymptomatic paroxysmal atrial fibrillation that occurred 26 days after the procedure. CONCLUSIONS: In this real-world Japanese study with almost one-third of patients aged >60 years, PFO closure with the AmplatzerTM PFO Occluder was performed successfully and safely, with a low incidence of procedure-related atrial arrhythmias.

Comparison of left atrial appendage measurements between conventional transesophageal echocardiography and "Virtual TEE" reconstructed from computed tomography for pre-procedural planning of device closure.

For pre-procedural planning of left atrial appendage (LAA) closure, sizing is crucial. Although transesophageal echocardiography (TEE) is a standard modality, cardiac computed tomography (CT) is also widely used. The virtual TEE (V-TEE) that our group developed enables us to reconstruct images similar to TEE images from CT images. The software should be helpful to understand and plan the procedure strategy. Accordingly, we investigated the utility of V-TEE. Sixty-six patients at 4 participating sites who completed both CT and TEE prior to LAA closure were included. The LAA diameter at the landing zone (LZ) for WATCHMAN™ device implantation was statistically compared at 0°, 45°, 90°, and 135° between V-TEE and TEE. Among 66 cases, only 3 cases were excluded due to poor imaging quality, and 63 cases were analyzed. The device LZ diameters based on V-TEE were strongly correlated with those based on TEE, despite the significantly greater diameter based on V-TEE with mean differences of 2.4 to 3.0 mm (all of them: P < 0.001). The discordances (V-TEE/TEE ratio) at most angles were significantly larger in the elliptical LAAs. V-TEE provides a valuable method for the evaluation of the LAA diameters. V-TEE-based measurements were larger than conventional TEE-based measurements, especially in cases of elliptical LAAs. The assessment by V-TEE has the potential benefit of ensuring proper device sizing regardless of the LAA morphology.

Transcatheter retrieval of atrial septal defect and patent ductus arteriosus occluder: a guidance for device retrieval based on comprehensive bench tests.

OBJECTIVES: The aim of this study is to establish a guidance for device retrieval based on comprehensive bench tests. BACKGROUND: Device embolisation remains a major complication in transcatheter closure of atrial septal defect and patent ductus arteriosus. Although percutaneous retrieval is feasible in the majority of cases, surgical retrieval may be required in complicated circumstances. However, the methods of transcatheter device retrieval have not been completely established. METHODS: Bench tests of device retrieval were performed to verify the appropriate retrieval method according to device type/size. The devices used for testing were Amplatzer Septal Occluder (Abbott, Chicago, IL, United States of America), Figulla Flex II (Occlutech GmbH, Jena, Germany), Amplatzer Duct Occluder-I (Abbott), Amplatzer Duct Occluder-II (Abbott), and Amplatzer Vascular Plug-II (Abbott). The retrieval equipment constituted diagnostic catheters (multipurpose catheter and right Judkins catheter, 4-Fr or 5-Fr, Gadelius Medical, Tokyo, Japan), delivery sheath and cables for each device, Amplatz goose neck snares (Medtronic, Minneapolis, MN, United States of America), OSYPKA CATCHER (Osypka ag, Rheinfelden-Herten, Germany), and OSYPKA LASSOS (Osypka). We investigated the retrieval equipment and sheath sizes required for a successful retrieval procedure for variously sized devices. RESULTS: For patent ductus arteriosus devices, the type of snare and the snaring position are considered important. For atrial septal defect devices, simple snare capture or a double-snare technique with a sufficiently large sheath is effective. Special care should be taken when using the OSYPKA CATCHER for device retrieval. CONCLUSIONS: The results of this study may assist in the selection of both capture devices and a retrieval sheath or a catheter for complete retrieval.

Impact of Preprocedural Frailty Status in Elderly Transvenous Pacemaker Recipients.

The number of TV-PM implantations in elderly people is increasing. Although frailty syndrome is common in elderly patients, the relationship between the pre-procedural frailty status and clinical outcomes has not been fully elucidated in elderly TV-PM recipients.This study included 103 consecutive patients over 80 years old who were newly implanted with a TV-PM (age 85.7 ± 4.2, 41.7% male). We assessed the relationship between the clinical outcome and predictive factors, especially for the pre-procedural frailty status after the TV-PM implantation. The pre-procedural frailty status was retrospectively assessed from the medical records and classified on the basis of impairments in 3 domains (walking, cognition, and activities of daily living). The primary endpoint was defined as a heart failure admission.During the follow-up period (4.1 ± 2.3 years), 20 patients (19.4%) met the primary endpoint. Frailty syndrome was identified in 40 patients (38.8%). In univariate analysis, the LVEF (HR 0.97, 95% CI 0.96-1.00 P = 0.0492), an RV pacing burden over 40% (HR 1.58, 95% CI 1.00-2.54 P = 0.0473), and presence of a frailty status (HR 1.82, 95% CI 1.13-2.87 P = 0.0134) were found to be statistically significant predictors for the study endpoint. In multivariate analysis, having frailty syndrome was the only predictive factor for a heart failure admission (HR 1.83, 95% CI 1.12-2.93 P = 0.0157).The presence of frailty syndrome and incidence of clinical events were high and a pre-procedural frailty status assessment was key in determining the clinical outcomes in TV-PM recipients over 80 years old.

Deep Learning-Based Recurrence Prediction of Atrial Fibrillation After Catheter Ablation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is an effective therapy for atrial fibrillation (AF). However, it the problem of AF recurrence remains. This study investigates whether a deep convolutional neural network (CNN) can accurately predict AF recurrence in patients with AF who underwent RFCA, and compares CNN with conventional statistical analysis.Methods and Results:Three-hundred and ten patients with AF after RFCA treatment, including 94 patients with AF recurrence, were enrolled. Nine variables are identified as candidate predictors by univariate Cox proportional hazards regression (CPH). A CNNSurv model for AF recurrence prediction was proposed. The model's discrimination ability is validated by a 10-fold cross validation method and measured by C-index. After back elimination, 4 predictors are used for model development, they are N-terminal pro-BNP (NT-proBNP), paroxysmal AF (PAF), left atrial appendage volume (LAAV) and left atrial volume (LAV). The average testing C-index is 0.76 (0.72-0.79). The corresponding calibration plot appears to fit well to a diagonal, and the P value of the Hosmer-Lemeshow test also indicates the proposed model has good calibration ability. The proposed model has superior performance compared with the DeepSurv and multivariate CPH. The result of risk stratification indicates that patients with non-PAF, higher NT-proBNP, larger LAAV and LAV would have higher risks of AF recurrence. CONCLUSIONS: The proposed CNNSurv model has better performance than conventional statistical analysis, which may provide valuable guidance for clinical practice.

Iatrogenic Atrial Septal Defect Requiring Transcatheter Closure Following Transcatheter Mitral Valve Repair.

BACKGROUND: Transcatheter mitral valve repair with the MitraClip system has been established in selected high-risk patients. The MitraClip procedure results in a relatively large iatrogenic atrial septal defect (iASD). This study aimed to investigate the prevalence and clinical course of iASD requiring transcatheter closure following the MitraClip procedure.Methods and Results: This study was conducted at all 59 institutions that perform transcatheter mitral valve repair with the MitraClip system in Japan. The data of patients on whom transcatheter iASD closure was performed were collected. Of the 2,722 patients who underwent the MitraClip procedure, 30 (1%) required transcatheter iASD closure. The maximum iASD size was 9±4 mm (range, 3-18 mm). The common clinical course of transcatheter iASD closure was hypoxemia with right-to-left shunt or right-sided heart failure with left-to-right shunt. Of the 30 patients, 22 (73%) required transcatheter closure within 24 h following the MitraClip procedure, including 12 with hypoxemia and 5 with right-sided heart failure complicated with cardiogenic shock. Of the 5 patients, 2 required mechanical circulatory support devices. Twenty-one patients immediately underwent transcatheter iASD closure, and hemodynamic deteriorations were resolved; however, 1 patient died without having undergone transcatheter closure. CONCLUSIONS: Transcatheter iASD closure was required in 1% of patients who underwent the MitraClip procedure. Many of these patients immediately underwent transcatheter iASD closure because of hypoxemia with right-to-left shunt or right-sided heart failure with left-to-right shunt.

Usefulness of an isoproterenol infusion to differentiate a left atrial appendage thrombus in a patient with nonvalvular atrial fibrillation.

A 78-year-old male with a history of a cardiac embolic stroke due to persistent AF and cerebral bleeding (CHADS2 score 4, HAS-BLED score 4) was referred to our hospital to implant a left atrial appendage (LAA) closure (LAAC) device. A trans esophageal echocardiography was performed and a high echoic lesion that was difficult to differentiate the spontaneous echo contrast or thrombus was found in the LAA cavity. After isoproterenol infusion, a high echoic lesion disappeared and we confirmed that it was not an LAA thrombus. Successful LAAC device implantation was performed without any thromboembolic events.

Safety and feasibility of implanting a transvenous implantable cardioverter defibrillator (TV-ICD) in the left axilla.

BACKGROUND: Transvenous implantable cardioverter defibrillator (TV-ICD) systems are commonly implanted in the left anterior chest because of an easier implantation and better defibrillation threshold. This study aimed to evaluate the safety and feasibility of left axillary implantations of TV-ICD systems. METHODS: We performed left axillary TV-ICD implantations and compared that to the major complication rate and operation time of the conventional TV-ICD implantation site (left anterior chest). The electrical parameter trends were also assessed in the left axilla group. RESULTS: Seventy-six consecutive patients were evaluated for the analysis. Thirty-one patients had their system implanted in the left axilla and the reasons for the implantations included 29 patients for cosmetic reasons and two for post-infection conditions. The operation time and major complication rate were similar between the two groups (left anterior chest vs. left axilla: 134±62.4 min vs. 114±33.5 min, p = .11, 1/45 patient, 2.2% [pocket hematoma] vs. 1/31 patient, 3.2% [lead dislodgement], p = .77). During the follow up period (4.9±2.3years), no lead interruptions were observed in either group. The electrical lead parameters at the time of the implantation and follow up were similar in the study group (R wave sensing 20.8±33.4 vs. 11.2±7.42 mv, p = .34; lead impedance 464±64.7 vs. 418±135ohm, p = .22; pacing threshold [at 0.4 ms] 1.0±0.76 vs. 1.21±0.93V, p = .49). CONCLUSION: TV-ICD implantations in the left axilla were performed safely without increasing the operation time as compared to the conventional ICD implantation site. ICD implantations in the left axilla are an alternative in those not suitable for implanting TV-ICDs in the conventional implantation site.

Evolution of patients with chronic thromboembolic pulmonary hypertension treated by balloon pulmonary angioplasty, according to their anticoagulant regimens.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) need anticoagulant therapy for life. Conventionally, vitamin K antagonists (VKAs) have been used and data about direct oral anticoagulants (DOACs) in CTEPH patients are lacking. Recently, balloon pulmonary angioplasty (BPA) has emerged as a treatment option for CTEPH. However, there are no reports examining the effects of DOACs and VKAs on the hemodynamics of patients after BPA. The aim of this study was to compare DOACs and VKAs regarding the hemodynamic changes in patients with CTEPH treated by BPA. Patients who were treated by BPA and underwent follow-up right heart catheterization 6 ± 1 months after the final BPA procedure were included in this study. The subjects were divided into two groups based on the anticoagulant administered, and hemodynamic changes (mean pulmonary artery pressure, mPAP; pulmonary vascular resistance, PVR; cardiac index, CI) were assessed. Of the 65 consecutive patients, 29 met the inclusion criteria (DOAC-group n = 14, VKA-group n = 15). Compared to pre-BPA, post-BPA hemodynamic parameters were improved in both groups. There was no significant difference between the two groups regarding pre-BPA, post-BPA, 6Mo-f/u and Δhemodynamic parameters (difference between 6Mo-f/u and post-BPA, ΔmPAP, - 0.7 ± 3.3 vs. - 2.7 ± 5.4 mmHg, p = 0.24; ΔPVR, - 41.9 ± 80.9 vs. - 16.4 ± 74.1 dyne s/cm5, p = 0.38; ΔCI, - 0.06 ± 0.35 vs. - 0.10 ± 0.35 L/min/m2, p = 0.80; DOAC-group vs. VKA-group, respectively). Hemodynamic improvement by BPA was maintained over 6 months of follow-up irrespective of the type of anticoagulant administered in CTEPH patients.

Lesion size and adjacent tissue damage assessment with high power and short duration radiofrequency ablation: comparison to conventional radiofrequency ablation power setting.

There is increased interest in creating high-power short duration (HPSD) ablation lesions in the field of atrial fibrillation (AF) radiofrequency ablation (RFA). We evaluated the lesion characteristics and collateral damage using two separate RFA protocols setting (HPSD: 50 W and 7 s vs control: 25 W and 30 s) in vitro model. Sixteen freshly killed porcine hearts were obtained, and the atrium and ventricle slabs were harvested for ablation. The each slabs were placed in a tissue bath with circulating 0.9% NaCl at maintained temperature 37 °C. RFA was performed with 4 mm tip irrigated force sensing catheter. All lesions were ablated under recording the electrical parameters using with Ensite Navx system (St. Jude Medical, St. Paul, Minnesota). After RFA, lesion characteristics were assessed for each lesion. Thirty-five lesions were made for each ablation protocol (total 70 lesions for analysis). Ablation parameters were similar between two groups (HPSD vs control; impedance drop (Ω): 34.2 ± 13.1 vs 36.1 ± 8.65 P = 0.49, contact force (g): 13.9 ± 4.37 vs 14.6 ± 5.09, P = 0.51, lesion size index: 4.8 ± 0.52 vs 4.73 ± 0.59, P = 0.62). Although the lesion volume was similar, the HPSD ablation creates wider but more shallower lesions compared to control group (HPSD vs control; lesion volume: 29.6 ± 18.1 mm3 vs 35.5 ± 17.1 mm3 P = 0.16, lesion diameter: 4.98 ± 0.91 mm vs 4.45 ± 0.74 mm P = 0.0095, lesion depth: 2.2 ± 0.76 mm vs 2.8 ± 1.56 mm P = 0.046). Of these, 38 lesions were assessed for adjacent tissue damage and adjacent tissue damages were more frequent seen in control group (HPSD vs control; 1/19 (5.26%) vs 6/19 (31.5%), P = 0.036). Effective lesions were made with HPSD, thereby reducing RFA procedure time. Although the lesion volume was similar between two groups, collateral damage was less seen in HPSD group attributed by lesion characteristics.

Impact of atrial mitral and tricuspid regurgitation on atrial fibrillation recurrence after ablation.

BACKGROUND: Atrial fibrillation (AF) induces functional mitral regurgitation (FMR) and tricuspid regurgitation (FTR) during atrial remodeling. FMR and FTR are associated with AF prognosis, but the effects for AF recurrence after ablation have not been determined conclusively. METHODS: Two hundred thirty nine patients who underwent AF ablation were enrolled. Forty five patients were excluded. In total, 194 patients were analyzed. FMR and FTR were assessed by echocardiography. The left atrial volume index (LAVI) was evaluated by contrast-enhanced computed tomography. RESULTS: Significant FMR and moderate FTR were observed in 15 (7.7%) and in 25 (12.9%) patients, respectively. The severity of tricuspid regurgitation (TR) significant correlated with age, NT-proBNP, and LAVI. During a 13.4 month follow-up period of, 39 patients (20.1%) demonstrated AF recurrence. In the Cox proportional-hazards model, E/e', FTR, and LAVI, were termed as predictor factors of AF recurrence (E/e'. hazard ratio [HR] = 1.117; P = 0.019, significant FTR. HR = 4.679; P = 0.041, LAVI. HR = 1.057; P = 0.003). Kaplan-Meier analysis showed that AF recurrence was more frequent in FTR compared with the nonsignificant FTR cases (log-rank, P = 0.001). Although survival analysis showed no difference with or without FMR, the presence of FMR and FTR was strongly associated with high-AF recurrence (log-rank, P = 0.004). CONCLUSIONS: AF recurrence was associated with E/e', LAVI, and extensive FTR. Specifically, the combination of FTR and FMR markedly worsens the AF prognosis.

The predictors of complications in balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

OBJECTIVES: The aims of this study were to (1) evaluate risk factors of complications of balloon pulmonary angioplasty (BPA) and (2) assess the mechanism of the complications. BACKGROUND: BPA represents a promising treatment option in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, the complication ratio differs across reports, and the causes remain controversial. METHODS: All complications found by angiography and non-contrasted computerized tomography (CT) immediately after BPA were recorded. New emergences of a ground-glass pattern or consolidation in CT after BPA that were not recognized on CT images before BPA were counted as pulmonary bleeding. Lesion morphologies were classified into four types (web, ring, abrupt narrowing and occlusive lesions) according to selective pulmonary angiography. RESULTS: Thirty patients consented to analysis of the BPA-related images, and 879 lesions (112 sessions) were evaluated. One hundred and twenty-two (99.2%) of 123 complications were confirmed to be associated with BPA procedures at the local area. In the multivariate analysis, occlusive lesions were the sole independent predictor of procedure-related complications (adjusted odds ratio 5.83, 95%CI [1.94-17.47], p = 0.002). Hemodynamic parameters were not predictors of complications. CT images after BPA presented the predictive value for the occurrence of hemoptysis. CONCLUSIONS: Almost all complications were attributed to operators' procedures. Lesion morphology was the sole predictor of BPA-related complications, while hemodynamic parameters were not associated with the frequency of complications. CT scan images after BPA were useful to identify bleeding complications and to predict hemoptysis.

Self-Expanding Nitinol Stent vs Percutaneous Transluminal Angioplasty in the Treatment of Femoropopliteal Lesions: 3-Year Data From the SM-01 Trial.

PURPOSE: To report the midterm outcomes of a trial comparing self-expanding nitinol stents to percutaneous transluminal angioplasty (PTA) with provisional stenting in the treatment of obstructive disease in the superficial femoral and popliteal arteries. MATERIALS AND METHODS: The SM-01 study ( ClinicalTrials.gov identifier NCT01183117), a single-blinded, multicenter, randomized controlled trial in Japan, enrolled 105 consecutive patients with de novo or postangioplasty restenotic femoropopliteal lesions; after removing protocol violations (1 from each group), 51 patients (mean age 74±8 years; 36 men) in the stent group and 52 patients (mean age 73±8 years; 35 men) in the PTA group were included in the intention-to-treat analysis. The groups were well-matched at baseline. Patients were followed to 36 months with duplex imaging. Three-year primary patency was assessed based on a duplex-derived peak systolic velocity ratio <2.5. Freedom from clinically-driven target vessel revascularization (TVR) and target lesions revascularization (TLR) were estimated using the Kaplan-Meier method. RESULTS: The technical success rate was higher (100% vs 48%, p<0.001) and the frequency of vascular dissection was lower (4% vs 31%, p<0.001) in the stent group. The S.M.A.R.T stent group had a higher 3-year primary patency rate (73% vs 51%, p=0.033). Freedom from clinically-driven TVR and TLR were not significantly different between the groups. CONCLUSION: The S.M.A.R.T. stent maintained a higher primary patency rate than PTA at 3 years in this randomized trial; the need for clinically-driven revascularization was similar for both therapies.

Analysis of Heart Rate Variability in a Patient with Takotsubo Cardiomyopathy Syndrome on the Actual Onset Day.

A healthy 73-year-old woman unpredictably developed Takotsubo cardiomyopathy syndrome (TTS) during Holter-electrocardiogram (ECG) recording. Thus, the complete chronological ECG data on the actual onset day of TTS were obtained. Many heart rate variability (HRV) parameters, including the low-frequency components (LF) and the high-frequency components (HF), on the actual onset day and in the healing phase were calculated. The interesting facts on the actual onset day were that the suppression of both LF and HF appeared earlier than the changes of the ECG waveform; and the LF/HF ratio remained within the normal range, although both LF and HF were markedly suppressed. The abnormality on the actual onset day was clear compared with the healing phase. It is noteworthy to obtain the chronological ECG data on the actual onset day of TTS in a healthy patient. The present data are unique in terms of being analyzed on the actual onset day. Although the HRV parameters, including LF and HF, were obviously abnormal, there is some skepticism about using HRV parameters as indices of cardiac autonomic activity. In the present case, it was concluded that the abnormality of cardiac autonomic activity contributed to the onset of TTS. These data are unlikely to ever be replicated, and we hope that this report helps elucidate the TTS mechanism.

Clinical Outcomes of Drug-Coated Balloons in Coronary Artery Disease Unsuitable for Drug-Eluting Stent Implantation.

BACKGROUND: The aim of this study was to investigate whether drug-coated balloon (DCB) treatment is effective for de novo coronary lesions that are unsuitable for drug-eluting stent (DES) implantation.Methods and Results:This retrospective study included 118 de novo lesions that were not suitable for DES implantation. Of the lesions, 40% was treated because of very small vessel disease. Patients with planned non-cardiac surgery and at high bleeding risk were 3% and 19%, respectively, and lesions that easily develop stent fracture comprised 26%. Clinically driven target lesion revascularization (TLR) was the primary endpoint. The rate of suboptimal lesion preparation before DCB treatment was set as the secondary endpoint. Optimal lesion preparation was defined as acquisition of Thrombolysis in Myocardial Infarction flow grade 3, minor coronary dissection, and residual stenosis ≤30%. The rate of suboptimal lesion preparation was 2.5% and 3 patients needed bail-out stenting. Accordingly, 115 patients were treated with a DCB. Clinically driven TLR had occurred in 8 patients (7.0%) at the 8-month follow-up. The presence of chronic total occlusion was identified as an independent predictor for TLR (odds 11.57; 95% confidence interval, 1.38-135.54; P=0.02). CONCLUSIONS: For lesions that are unsuitable for stent implantation, stent-less intervention using a DCB should be considered initially. The present study also highlighted that lesion preparation is key to a successful DCB strategy.

A potentially crucial role of the PKD1 C-terminal tail in renal prognosis.

BACKGROUND: Autosomal dominant polycystic disease (ADPKD) often results in renal failure. Recently, allelic influences of PKD1 mutation types on renal survival were extensively investigated. Here, we analyzed integrated influences of PKD1 mutation types and positions on renal survival. METHODS: We included 338 (82 pedigrees) and 72 (12 pedigrees) patients with PKD1 and PKD2 mutations, respectively, identified through comprehensive gene analysis of 101 probands with ADPKD. Genetic testing was performed using next-generation sequencing, long-range PCR, and multiplex ligation-dependent probe amplification. Pathogenic mutations were identified by a software package-integrated seven databases and provided access to five cloud-based computing systems. RESULTS: Mean renal survivals of carriers with PKD1 non-truncating-type mutations at positions upstream of G-protein-coupled receptor proteolytic site (GPS-upstream domain), transmembrane domain, or cytoplasmic C-terminal tail (CTT) domain were 70.2, 67.0, and 50.1 years, respectively (P < 0.0001); renal survival was shorter for mutation positions closer to CTT domain, suggesting its crucial role in renal prognosis. Furthermore, in truncating-type mutations, strong inactivation is anticipated on nucleotides downstream from the mutation site, implying CTT domain inactivation irrespective of mutation site. Shorter mean renal survival was found for PKD1 truncating-type than non-truncating-type mutation carriers (P = 0.0348); mean renal survival was not different between PKD1 3'- and 5'-region truncating-type mutation carriers (P = 0.4375), but was shorter in PKD1 3'-region than in 5'-region non-truncating-type mutation carriers (P = 0.0014). Variable strength of CTT domain inactivation might account for these results. CONCLUSIONS: Aforementioned findings indicate that CTT domain's crucial role in renal prognosis needs further investigation by larger studies (ClinicalTrials.gov; NCT02322385).

Congenital Absence of Left Atrial Appendage Diagnosed by Multimodality Imaging.

A 70-years-old male with a history of hypertension and drug resistant paroxysmal atrial fibrillation (AF) presented to our hospital for catheter ablation to his symptomatic AF. He had no prior surgical or percutaneous procedure to close or exclude the left atrial appendage (LAA). A transesophageal echocardiography (TEE) was performed to rule out intra-cardiac thrombus prior to the ablation procedure. Although the TEE imaging at multiple acquisition angles was obtained, the LAA could not be visualized and an absence of the LAA was suspected. An absence of the LAA was confirmed using cardiac computed tomography (CT), which included 3D reconstruction. Additionally, the LAA was not visualized with left atrium (LA) angiography. During the ablation procedure, 3D voltage mapping in LA was created and no low voltage area or abnormal potential was recorded around the usual root location of the LAA. Successful electrical pulmonary vein isolation was achieved with no major complications. After six months of follow-up, the patient remained in sinus rhythm without any antiarrhythmic drugs and showed no related clinical symptoms. He stopped his anticoagulation therapy due to lack of evidence of AF recurrence and an absence of LAA. Multimodality imaging allowed us to identify the congenital absence of LAA.

Angiogenic, inflammatory and immunologic markers in predicting response to sunitinib in metastatic renal cell carcinoma.

The objective of this prospective study was to identify baseline angiogenic and inflammatory markers in serum as well as the baseline levels of immune cells in whole blood to predict progression-free survival in patients with metastatic renal cell carcinoma treated with sunitinib. Blood samples were collected at baseline in all 90 patients to analyze serum angiogenic and inflammatory markers together with peripheral blood immunological marker. The association between each marker and sunitinib efficacy was analyzed. Univariate and multivariate Cox proportional model analyses were used to assess the correlation between those markers with survival. Baseline levels of interleukin-6, interleukin-8, high sensitivity C-reactive protein and myeloid-derived suppressor cells were significantly higher in patients who progressed when compared with those with clinical benefit. Analysis by the Cox regression model showed that baseline interleukin-8, high sensitivity C-reactive protein and percentage of T helper type 1 cells were significantly associated with progression-free survival in univariate analysis. Furthermore, in multivariate analysis, those three markers were independent indices to predict progression-free survival. In conclusion, angiogenic (interleukin-8), inflammatory (interleukin-6, high sensitivity C-reactive) and immunologic (myeloid-derived suppressor cells, percentage of T helper type 1 cells) markers at baseline would predict the response to sunitinib therapy and/or disease progression in patients with metastatic renal cell carcinoma.