[Emergent Transcatheter Aortic Valve Implantation for Degenerated Surgical Aortic Valve Under Local Anesthesia:Report of a Case].

An 89-year-old man who had undergone aortic valve replacement with a 21 mm Mosaic bioprosthetic valve at another hospital 14 years ago was admitted to the emergency room for a sudden respiratory distress two days prior and was diagnosed with severe aortic regurgitation( AR) caused by valve insufficiency and acute heart failure secondary to low cardiac function. Upon admission, he was found to have severe hypoxia with PaO2 of 40 mmHg range, and transcatheter aortic valve replacement (TAVI, TAV in SAV) with a 20 mm SAPIEN3 was performed under local anesthesia for fear of hypotension while under general anesthesia. After confirming that AR had completely disappeared, the patient was intubated and discharged from the operating room on a mechanical ventilator. The patient was weaned from the ventilator on the second postoperative day and was transferred to the other hospital for rehabilitation, 48 days postoperatively. Although there is no report on the comparative study of anesthesia methods for emergency transcatheter aortic valve implantation( TAVI), TAVI under regional anesthesia is minimally invasive with a lower risk for hypotension than general anesthesia. Therefore, we believe it is useful for patients with acute heart failure and hypotension. In addition, it is important to use a balloon expandable valve with excellent implantability to complete the procedure in a short time.

Rivaroxaban Monotherapy vs Combination Therapy With Antiplatelets on Total Thrombotic and Bleeding Events in Atrial Fibrillation With Stable Coronary Artery Disease: A Post Hoc Secondary Analysis of the AFIRE Trial.

Importance: Appropriate regimens of antithrombotic therapy for patients with atrial fibrillation (AF) and coronary artery disease (CAD) have not yet been established. Objective: To compare the total number of thrombotic and/or bleeding events between rivaroxaban monotherapy and combined rivaroxaban and antiplatelet therapy in such patients. Design, Setting, and Participants: This was a post hoc secondary analysis of the Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease (AFIRE) open-label, randomized clinical trial. This multicenter analysis was conducted from February 23, 2015, to July 31, 2018. Patients with AF and stable CAD who had undergone percutaneous coronary intervention or coronary artery bypass grafting 1 or more years earlier or who had angiographically confirmed CAD not requiring revascularization were enrolled. Data were analyzed from September 1, 2020, to March 26, 2021. Interventions: Rivaroxaban monotherapy or combined rivaroxaban and antiplatelet therapy. Main Outcomes and Measures: The total incidence of thrombotic, bleeding, and fatal events was compared between the groups. Cox regression analyses were used to estimate the risk of subsequent events in the 2 groups, with the status of thrombotic or bleeding events that had occurred by the time of death used as a time-dependent variable. Results: A total of 2215 patients (mean [SD] age, 74 [8.2] years; 1751 men [79.1%]) were included in the modified intention-to-treat analysis. The total event rates for the rivaroxaban monotherapy group (1107 [50.0%]) and the combination-therapy group (1108 [50.0%]) were 12.2% (135 of 1107) and 19.2% (213 of 1108), respectively, during a median follow-up of 24.1 (IQR, 17.3-31.5) months. The mortality rate was 3.7% (41 of 1107) in the monotherapy group and 6.6% (73 of 1108) in the combination-therapy group. Rivaroxaban monotherapy was associated with a lower risk of total events compared with combination therapy (hazard ratio, 0.62; 95% CI, 0.48-0.80; P < .001). Monotherapy was an independent factor associated with a lower risk of subsequent events compared with combination therapy. The mortality risk after a bleeding event (monotherapy, 75% [6 of 8]; combination therapy, 62.1% [18 of 29]) was higher than that after a thrombotic event (monotherapy, 25% [2 of 8]; combination therapy, 37.9% [11 of 29]). Conclusions and Relevance: Rivaroxaban monotherapy was associated with lower risks of total thrombotic and/or bleeding events than combination therapy in patients with AF and stable CAD. Tapered antithrombotic therapy with a sole anticoagulant should be considered in these patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02642419.

The impact of kidney function in patients on antithrombotic therapy: a post hoc subgroup analysis focusing on recurrent bleeding events from the AFIRE trial.

BACKGROUND: The success of antithrombotic therapies is assessed based on thrombotic and bleeding events. Simultaneously assessing both kinds of events might be challenging, and recurrent bleeding events are often ignored. We tried to confirm the effects of kidney function on outcome events in patients undergoing antithrombotic therapy. METHODS: As a post hoc subgroup analysis of the Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial, a randomized clinical trial with a median follow-up of 36 months, patients were divided into high and low estimated glomerular filtration rate (eGFR) groups with a cutoff value of 50 mL/min. The cumulative incidence of bleeding and crude incidence of recurrent bleeding per 100 patient-years were calculated. We used the Cox regression model with multiple failure time data for recurrent bleeding events. RESULTS: Among 2092 patients, 1386 (66.3%) showed high eGFR. The cumulative bleeding events per 100 patients at 1 year were 5.4 and 6.2 in the high and low eGFR groups, respectively. The difference continued to increase over time. The hazard ratio for time to the first bleeding event in the high eGFR group was 0.875 (95% confidence interval 0.701-1.090, p = .234) and that for the first composite event was 0.723 (95% confidence interval 0.603-0.867, p < .000). The recurrent bleeding events per 100 person-years were 11.3 and 15.3 in the high and low eGFR groups, respectively, with a rate ratio of 0.738 (95% confidence interval 0.615-0.886, p = .001). During the observation period, the risk of bleeding changed with time. It peaked soon after the study enrollment in both groups. It decreased continuously in the high eGFR group but remained high in the low eGFR group. CONCLUSIONS: We reaffirmed that kidney function affects bleeding events in patients on antithrombotic therapy, considering recurrent events. Patients should have detailed discussions with physicians regarding the possible bleeding events when continuing antithrombotic therapy, especially in patients with decreased kidney function. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000016612 . ClinicalTrials.gov, NCT02642419 . Registered on 21 October 2015.

Antithrombotic Therapy for Atrial Fibrillation and Coronary Artery Disease in Patients With Prior Atherothrombotic Disease: A Post Hoc Analysis of the AFIRE Trial.

Background Among patients with atrial fibrillation and stable coronary artery disease, those with histories of atherothrombotic disease are at high-risk for future ischemic events. This study investigated the efficacy and safety of rivaroxaban monotherapy in patients with atrial fibrillation, coronary artery disease, and histories of atherothrombotic disease. Methods and Results This was a post hoc subanalysis of the AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial. Patients with non-valvular atrial fibrillation and coronary artery disease were recruited and randomized to receive the rivaroxaban monotherapy or combination therapy with rivaroxaban plus antiplatelet drug. For the purpose of this sub-study, participants were divided into 2 subgroups, including the atherothrombosis group (those with histories of myocardial infarction, stroke, and/or peripheral artery disease; n=1052, 47.5%) and non-atherothrombosis group (n=1163, 52.5%). The efficacy end point included cardiovascular events or all-cause death, while the safety end point was major bleeding. Net adverse events consisted of all-cause death, myocardial infarction, stroke, or major bleeding. In the atherothrombosis group, rivaroxaban monotherapy was significantly associated with a lower risk of net adverse events when compared with combination therapy (hazard ratio [HR], 0.50; 95% CI, 0.34-0.74; P<0.001), with a decrease in both efficacy (HR, 0.68; 95% CI, 0.47-0.99; P=0.044) and safety (HR, 0.37; 95% CI, 0.19-0.71; P=0.003) end points. By contrast, there were no differences between treatment outcomes for the non-atherothrombosis group. Conclusions Rivaroxaban monotherapy significantly reduced net adverse events as compared with combination therapy for patients with atrial fibrillation, coronary artery disease, and prior atherothrombotic disease. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000016612. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02642419.

Aspirin versus P2Y12 inhibitors with anticoagulation therapy for atrial fibrillation.

OBJECTIVE: Patients with coronary artery disease (CAD) and atrial fibrillation (AF) can be treated with multiple antithrombotic therapies including antiplatelet and anticoagulant therapies; however, this has the potential to increase bleeding risk. Here, we aimed to evaluate the efficacy and safety of P2Y12 inhibitors and aspirin in patients also receiving anticoagulant therapy. METHODS: We evaluated patients from the Atrial Fibrillation and Ischaemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial who received rivaroxaban plus an antiplatelet agent; the choice of antiplatelet agent was left to the physician's discretion. The primary efficacy and safety end points, consistent with those of the AFIRE trial, were compared between P2Y12 inhibitors and aspirin groups. The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularisation or death from any cause. The primary safety end point was major bleeding according to the International Society on Thrombosis and Haemostasis criteria. RESULTS: A total of 1075 patients were included (P2Y12 inhibitor group, n=297; aspirin group, n=778). Approximately 60% of patients were administered proton pump inhibitors (PPIs) and there was no significant difference in PPI use in the groups. There were no significant differences in the primary end points between the groups (efficacy: HR 1.31; 95% CI 0.88 to 1.94; p=0.178; safety: HR 0.79; 95% CI 0.43 to 1.47; p=0.456). CONCLUSIONS: There were no significant differences in cardiovascular and bleeding events in patients with AF and stable CAD taking rivaroxaban with P2Y12 inhibitors or aspirin in the chronic phase. TRIAL REGISTRATION NUMBER: UMIN000016612; NCT02642419.

Rivaroxaban monotherapy versus combination therapy according to patient risk of stroke and bleeding in atrial fibrillation and stable coronary disease: AFIRE trial subanalysis.

BACKGROUND: In the AFIRE trial, rivaroxaban monotherapy was noninferior to combination therapy with rivaroxaban and an antiplatelet agent for thromboembolic events or death, and superior for major bleeding in patients with atrial fibrillation (AF) and stable coronary artery disease. Little is known about impacts of stroke and bleeding risks on the efficacy and safety of rivaroxaban monotherapy. METHODS: In this subanalysis of the AFIRE trial, we assessed the risk of stroke and bleeding by the CHADS2, CHA2DS2-VASc, and HAS-BLED scores. The primary efficacy end point was the composite of stroke, systemic embolism, myocardial infarction (MI), unstable angina requiring revascularization, or death from any cause. The primary safety end point was major bleeding defined by the International Society on Thrombosis and Haemostasis. RESULTS: Rivaroxaban monotherapy significantly reduced the primary efficacy and safety end points with no evidence of differential effects by stroke risk (CHADS2, p for interaction = 0.727 for efficacy, 0.395 for safety; CHA2DS2-VASc, p for interaction = 0.740 for efficacy, 0.265 for safety) or bleeding risk (HAS-BLED, p for interaction = 0.581 for efficacy, 0.225 for safety). There was also no evidence of statistical heterogeneity across patient risk categories for other end points; stroke or systemic embolism, ischemic stroke, hemorrhagic stroke, MI, MI or unstable angina, death from any cause, any bleeding, or net adverse clinical events. CONCLUSIONS: The advantages of rivaroxaban monotherapy compared with those of combination therapy with respect to all prespecified end points, including thromboembolism, bleeding, and mortality were similar across patients with AF and stable coronary artery disease, irrespective of their risk for stroke and bleeding. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry number, UMIN000016612, and ClinicalTrials.gov number, NCT02642419.

Efficacy of oral myofunctional therapy in middle-aged to elderly patients with obstructive sleep apnoea treated with continuous positive airway pressure.

BACKGROUND: Oral myofunctional therapy (MFT) is an effective treatment for mild-to-moderate obstructive sleep apnoea (OSA) in middle-aged patients. However, few reports have described its use in elderly patients with moderate and severe OSA. Moreover, no studies have examined the relationship between changes in tongue pressure with MFT and the severity of OSA. OBJECTIVE: We conducted an interventional study using MFT to evaluate the effect of MFT on middle-to-senior-aged patients with moderate or severe OSA and compared changes in apnoea-hypopnea index (AHI) and tongue pressure. METHODS: Thirty-two OSA patients (≥45 years) treated with continuous positive airway pressure (CPAP) were included. MFT was performed in parallel with CPAP. Three days after CPAP discontinuation, polysomnographies were performed and tongue pressures were measured before and after MFT. RESULTS: Patients were 69.3 ± 1.5 years old. After 6 months of MFT, AHI decreased significantly from 34.7 to 29.0/h (P = .03), while tongue pressure significantly increased from 35.9 to 45.6 kPa (P < .01). Seven patients (22%), including 6 of the 12 patients with moderate OSA (50%), experienced successful CPAP discontinuation. CONCLUSIONS: MFT can be a useful intervention even among middle-aged to elderly patients with OSA. Increased tongue pressure may have contributed to the AHI improvement. Clinical trials: Trial registration at www.umin.ac.jp UMIN000027547.

Electrophysiological features and radiofrequency catheter ablation of accessory pathways associated with atrioventricular discordance.

INTRODUCTION: Although a high prevalence of the presence of an accessory pathway (AP) associated with atrioventricular (AV) discordance has been reported, a case series of its characteristics and the results of catheter ablation (CA) have not been sufficiently documented. METHODS AND RESULTS: We retrospectively examined 11 consecutive patients with atrioventricular discordance who underwent CA for atrioventricular reciprocating tachycardia (AVRT) via an AP and planned cardiac surgery after CA. Orthodromic AVRTs were induced in 10 patients via AP, but no antidromic/duodromic AVRT was induced in any of the cases. A total of 13 APs were identified, and all of them were located around the anatomical tricuspid valve (TV) annulus, including two Ebsteinoid valves. The APs were predominantly located posteriorly, posterolaterally, and posteroseptally on the TV in nine patients (82%). Two patients (18%) had multiple APs or a single broad AP. Four (36%) and three (27%) patients showed twin AVNs and other supraventricular tachycardias (SVTs) except AVRT via the AP. Ten patients (91%) had acute successful CA in the first session, except for one patient with multiple APs who required the third session to eliminate all APs before the planned Fontan surgery. There were no major complications associated with CA. Seven of eight patients who underwent cardiac surgery after CA did not experience peri-/postoperative SVT. CONCLUSION: APs in patients with AV discordance are usually associated with the anatomical TV annulus. CA of an AP in AV discordance is highly effective and recommended to reduce the risk of SVT. The coexistence of twin AVNs and other SVTs should be considered during CA of an AP in AV discordance.

Antithrombotic Therapy for Atrial Fibrillation with Stable Coronary Disease.

BACKGROUND: There are limited data from randomized trials evaluating the use of antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease. METHODS: In a multicenter, open-label trial conducted in Japan, we randomly assigned 2236 patients with atrial fibrillation who had undergone percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) more than 1 year earlier or who had angiographically confirmed coronary artery disease not requiring revascularization to receive monotherapy with rivaroxaban (a non-vitamin K antagonist oral anticoagulant) or combination therapy with rivaroxaban plus a single antiplatelet agent. The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause; this end point was analyzed for noninferiority with a noninferiority margin of 1.46. The primary safety end point was major bleeding, according to the criteria of the International Society on Thrombosis and Hemostasis; this end point was analyzed for superiority. RESULTS: The trial was stopped early because of increased mortality in the combination-therapy group. Rivaroxaban monotherapy was noninferior to combination therapy for the primary efficacy end point, with event rates of 4.14% and 5.75% per patient-year, respectively (hazard ratio, 0.72; 95% confidence interval [CI], 0.55 to 0.95; P<0.001 for noninferiority). Rivaroxaban monotherapy was superior to combination therapy for the primary safety end point, with event rates of 1.62% and 2.76% per patient-year, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P = 0.01 for superiority). CONCLUSIONS: As antithrombotic therapy, rivaroxaban monotherapy was noninferior to combination therapy for efficacy and superior for safety in patients with atrial fibrillation and stable coronary artery disease. (Funded by the Japan Cardiovascular Research Foundation; AFIRE UMIN Clinical Trials Registry number, UMIN000016612; and ClinicalTrials.gov number, NCT02642419.).

The Baseline Nutritional Status Predicts Long-Term Mortality in Patients Undergoing Endovascular Therapy.

INTRODUCTION: Peripheral artery disease (PAD) occurs at an advanced stage of atherosclerosis and its comorbidities are associated with poor prognoses. Malnutrition is related to the severity of atherosclerosis in patients with cardiovascular disease and it predicts mortality. The Controlling Nutritional Status (CONUT) score is calculated from serum albumin concentration, peripheral lymphocyte count and total cholesterol concentration, and it robustly represents the nutritional status of hospitalized patients. This study aimed to determine the prognostic value of the CONUT score in patients with peripheral artery disease (PAD) who were undergoing endovascular therapy (EVT). METHODS AND RESULTS: This study included 628 PAD patients who underwent EVT between 2013 and 2017 and were assigned to low (CONUT score 0: n = 81), mild (CONUT score 1-2: n = 250), moderate (CONUT score 3-4: n = 169), and high (CONUT score ≥ 5: n = 128) risk groups. The study's primary endpoint was any death. Patients in the groups with higher CONUT scores were more likely to have chronic kidney disease (p < 0.001), impaired left ventricular ejection fractions (p < 0.001), and critical limb ischemia (p < 0.001) on admission. During follow-up, 95 patients (15%) died. Kaplan-Meier analyses revealed that the patients with higher CONUT scores had lower survival rates (p < 0.001; log-rank trend test). Multivariate Cox regression analyses showed that following adjustments for the confounding factors, a higher CONUT score was significantly associated with any death (hazard ratio, 1.15; 95% confidence interval, 1.03-1.30). CONCLUSION: The simple index CONUT score at the time of EVT may predict long-term mortality in PAD patients.

Comparison Between Contact Force Monitoring and Unipolar Signal Modification as a Guide for Catheter Ablation of Atrial Fibrillation: Prospective Multi-Center Randomized Study.

BACKGROUND: Both contact force monitoring (CFM) and unipolar signal modification (USM) are guides for ablation, which improve the efficacy of pulmonary vein isolation of atrial fibrillation. We sought to compare the outcomes of atrial fibrillation ablation guided by CFM or USM. METHODS: A total of 136 patients with paroxysmal atrial fibrillation underwent a circumferential pulmonary vein isolation using CF sensing ablation catheters and were randomly assigned to undergo catheter ablation guided by either CFM (CFM-guided group: n=70) or USM (USM-guided group: n=66). In the USM-guided group, each radiofrequency application lasted until the development of completely positive unipolar electrograms. In the CFM-guided group, a CF of 20 g (range, 10-30 g) and minimum force-time integral of 400 g were the targets for each radiofrequency application. The primary end point was freedom from any atrial tachyarrhythmia recurrence without antiarrhythmic drugs at 12-months of follow-up. RESULTS: The cumulative freedom from recurrences at 12-months was 85% in the USM-guided group and 70% in the CFM-guided group (P=0.031). The incidence of time-dependent and ATP-provoked early electrical reconnections between the left atrium and PVs, procedural time, fluoroscopic time, and average force-time integral, did not significantly differ between the 2 groups. The radiofrequency time for the pulmonary vein isolation was shorter in the USM-guided group than CFM-guided group but was not statistically significant (P=0.077). CONCLUSIONS: USM was superior to CFM as an end point for radiofrequency energy deliveries during the pulmonary vein isolation in patients with paroxysmal atrial fibrillation in terms of the 12-month recurrence-free rate. CLINICAL TRIAL REGISTRATION: URL: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000021127.

Is It Necessary to Achieve a Complete Box Isolation in the Case of Frequent Esophageal Temperature Rises? Feasibility of Shifting to a Partial Box Isolation Strategy for Patients With Non-Paroxysmal Atrial Fibrillation.

INTRODUCTION: There are some cases with frequent luminal esophageal temperature (LET) rises despite titrating the radiofrequency energy while creating a linear lesion for the Box isolation of atrial fibrillation (AF). Little is known about the feasibility of redesigning the ablation lines for a modified Box isolation strategy to prevent fatal esophageal injury in those cases. METHODS AND RESULTS: Two hundred and seventeen patients who underwent a Box isolation of non-paroxysmal AF were evaluated. We divided them into 2 groups, patients in whom a box lesion set of the entire posterior left atrium had been achieved (complete Box isolation [CBI]; n = 157) and those in whom 2 additional peri-esophageal vertical lines were created at both the right and left ends of the esophagus, and those areas were left with an incomplete isolation when frequent rapid LET rises above 39.0 °C were observed while creating the floor line (partial Box isolation [PBI]; n = 60). During 20.1 ± 13.9 months of follow-up, the arrhythmia-free rates were 54.1% in the CBI group versus 48.3% in the PBI group (P = 0.62). In the second session, a complete Box isolation was highly achieved even in the PBI group (94.3% vs. 83.3%, respectively; P = 0.17) and after 2 procedures, the arrhythmia-free rates increased to 75.2% vs. 68.3%, respectively (P = 0.34). There was no symptomatic esophageal injury in the PBI group. CONCLUSION: In the case of frequent LET rises while creating the linear lesions for the Box isolation strategy for non-paroxysmal AF, shifting to the PBI strategy was feasible.

Waon Therapy for Managing Chronic Heart Failure　- Results From a Multicenter Prospective Randomized WAON-CHF Study.

BACKGROUND: Waon therapy improves heart failure (HF) symptoms, but further evidence in patients with advanced HF remains uncertain. METHODS AND RESULTS: In 19 institutes, we prospectively enrolled hospitalized patients with advanced HF, who had plasma levels of B-type natriuretic peptide (BNP) >500 pg/ml on admission and BNP >300 pg/ml regardless of more than 1 week of medical therapy. Enrolled patients were randomized into Waon therapy or control groups. Waon therapy was performed once daily for 10 days with a far infrared-ray dry sauna maintained at 60℃ for 15 min, followed by bed rest for 30 min covered with a blanket. The primary endpoint was the ratio of BNP before and after treatment. In total, 76 Waon therapy and 73 control patients (mean age 66 years, men 61%, mean plasma BNP 777 pg/ml) were studied. The groups differed only in body mass index and the frequency of diabetes. The plasma BNP, NYHA classification, 6-min walk distance (6MWD), and cardiothoracic ratio significantly improved only in the Waon therapy group. Improvements in NYHA classification, 6MWD, and cardiothoracic ratio were significant in the Waon therapy group, although the change in plasma BNP did not reach statistical significance. No serious adverse events were observed in either group. CONCLUSIONS: Waon therapy, a holistic soothing warmth therapy, showed clinical advantages in safety and efficacy among patients with advanced HF.

Localized reentrant tachycardia in the aorta contiguity region mimicking perimitral atrial flutter in the context of atrial fibrillation ablation.

We describe a case with a focal atrial tachycardia (AT) masquerading as perimitral atrial flutter revealed after circumferential pulmonary vein antral isolation for atrial fibrillation. It was successfully terminated and became noninducible by a point ablation on the left atrial anterior wall (LAAW) near the mitral annulus in contact with the aortic root and on the left superior pulmonary vein-left atrial appendage ridge, without any linear ablation, using electroanatomical mapping and conventional precise mapping with a maximum amplified gain within the low-voltage area. The AT revealed in our case was an LAAW-aorta contiguity area-related AT.

A connexin40 mutation associated with a malignant variant of progressive familial heart block type I.

BACKGROUND: Progressive familial heart block type I (PFHBI) is a hereditary arrhythmia characterized by progressive conduction disturbances in the His-Purkinje system. PFHBI has been linked to genes such as SCN5A that influence cardiac excitability but not to genes that influence cell-to-cell communication. Our goal was to explore whether nucleotide substitutions in genes coding for connexin proteins would associate with clinical cases of PFHBI and if so, to establish a genotype-cell phenotype correlation for that mutation. METHODS AND RESULTS: We screened 156 probands with PFHBI. In addition to 12 sodium channel mutations, we found a germ line GJA5 (connexin40 [Cx40]) mutation (Q58L) in 1 family. Heterologous expression of Cx40-Q58L in connexin-deficient neuroblastoma cells resulted in marked reduction of junctional conductance (Cx40-wild type [WT], 22.2±1.7 nS, n=14; Cx40-Q58L, 0.56±0.34 nS, n=14; P<0.001) and diffuse localization of immunoreactive proteins in the vicinity of the plasma membrane without formation of gap junctions. Heteromeric cotransfection of Cx40-WT and Cx40-Q58L resulted in homogenous distribution of proteins in the plasma membrane rather than in membrane plaques in ≈50% of cells; well-defined gap junctions were observed in other cells. Junctional conductance values correlated with the distribution of gap junction plaques. CONCLUSIONS: Mutation Cx40-Q58L impairs gap junction formation at cell-cell interfaces. This is the first demonstration of a germ line mutation in a connexin gene that associates with inherited ventricular arrhythmias and emphasizes the importance of Cx40 in normal propagation in the specialized conduction system.

Successful catheter ablation and documentation of the activation and propagation pattern during a left atrial focal tachycardia in a patient with cor triatriatum sinister.

We report a case of an atrial tachycardia (AT) originating from the left atrium (LA) associated with cor triatriatum sinister. Electroanatomical mapping of the 2 subdivided chambers of the LA during the AT revealed a centrifugal activation pattern from the posterior wall of the accessory chamber near the left superior pulmonary vein. The propagation map on the CARTO system revealed that the AT wave front spread centrifugally over the "accessory chamber," turned around the edge of the membrane subdividing the LA, and then spread over the "main chamber." A single radiofrequency application successfully abolished the AT.