Telethonin variants found in Brugada syndrome, J-wave pattern ECG, and ARVC reduce peak Nav 1.5 currents in HEK-293 cells.

BACKGROUND: Telethonin (TCAP) is a Z-disk protein that maintains cytoskeletal integrity and various signaling pathways in cardiomyocytes. TCAP is shown to modulate α-subunit of the human cardiac sodium channel (hNav 1.5) by direct interactions. Several TCAP variants are found in cardiomyopathies. We sought to investigate whether TCAP variants are associated with arrhythmia syndromes. METHODS: Mutational analyses for TCAP were performed in 303 Japanese patients with Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy, and J-wave pattern ECG. Using patch-clamp techniques, electrophysiological characteristics of hNav 1.5 were studied in HEK-293 cells stably expressing hNav 1.5 and transiently transfected with wild-type (WT) or variant TCAP. RESULTS: We identified two TCAP variants, c.145G>A:p.E49K and c.458G>A:p.R153H, in four individuals. p.E49K was found in two patients with ARVC or BrS. p.R153H was found in two patients with BrS or J-wave pattern ECG. No patient had variant hNav 1.5. Patch-clamp experiments demonstrated that peak sodium currents were significantly reduced in cells expressing p.R153H and p.E49K compared with WT-TCAP (66%, p.R153H; 72%, p.E49K). Voltage dependency of peak IV curve was rightward-shifted by 5 mV in cells expressing p.E49K compared with WT-TCAP. Voltage dependency of activation was not leftward-shifted by p.R153H, while voltage dependency of steady-state inactivation was leftward-shifted by p.E49K. CONCLUSIONS: We found two TCAP variants in the patients with BrS, J-wave pattern ECG, and ARVC that can cause loss-of-function of the hNav 1.5 in heterologous expression systems. Our observation suggests that these variants might impair INa and be associated with the patients' electrophysiological phenotypes. Further studies linking our experimental data to clinical phenotypes are warranted.

Epicardial flow in the right ventricular wall on echocardiography: A sign of chronic total occlusion of left anterior descending artery.

Transthoracic coronary Doppler echocardiography (TCDE) can be useful for the detection of chronic total occlusion (CTO) of the proximal left anterior descending coronary artery (LAD) noninvasively, by detecting retrograde flow through the distal LAD or its septal branch. This intriguing case report details the detection of abnormal blood flow in the right ventricular free wall by TCDE. This detection of abnormal flow may be useful to predict CTO of the LAD, even in the absence of retrograde flow in the LAD and its septal branch.

Relationship between coronary diastolic pressure indexes during the wave-free period and a novel pressure-derived index: Diastolic pressure ratio at the optimal point.

OBJECTIVES: We aimed to determine the diastolic pressure ratio at the optimal point (DROP) using a simple measurement algorithm and to compare DROP with distal coronary-to-aortic pressure ratios during the wave-free period (PRWFP ) and at the mid-diastolic point (PRMD ). METHODS: Distal coronary and aortic pressures were measured from color pressure images of 440 beats in 48 patients with coronary stenoses. The DROP measurement point was 67% for one beat between the two rising points on the aortic pressure curve according to the distribution of the wave-free period and the mid-diastolic point. RESULTS: DROP correlated closely with PRWFP (r = 0.993, P < 0.0001) and PRMD (r = 0.997, P < 0.0001). The diagnostic efficiency was excellent (area under the receiver-operating characteristic curve, 0.997) for both PRWFP ≤ 0.89 (specificity, 0.99; sensitivity, 0.96) and PRMD ≤ 0.89 (specificity, 0.95; sensitivity, 1.00). CONCLUSIONS: A simple pressure-derived physiological marker of coronary stenosis, DROP, might represent other diastolic pressure indexes with a numerical equivalency to the instantaneous wave-free ratio. DROP can be measured automatically assuming that the rising points on the aortic pressure curve are detectable. However, further large-scale clinical investigations are needed to determine whether DROP could contribute to the further generalization of physiology-guided percutaneous coronary intervention.

Current Trends in Implantable Cardioverter-Defibrillator Therapy in Children　- Results From the JCDTR Database.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) are being used with increasing frequency in children. Our aim was to examine the current trend of pediatric ICD implantation in Japan. Methods and Results: Data was extracted from the Japanese Cardiac Device Treatment Registry (JCDTR), a nation-wide registry started in 2006. All patients aged less than 18 years who had an ICD implantation registered between 2006 and 2016 were included in the analysis. A total of 201 patients were included, with a median age of 16 years (range 1-18). The underlying cardiac diagnosis was primary electrical disease (67%), cardiomyopathy (26%) and congenital heart disease (4%), with idiopathic ventricular fibrillation (29%) and long QT syndrome (21%) being the 2 most common diagnoses. Implantation indication was primary prevention in only 30 patients (15%). There were 27 patients (13%) aged ≤12 years, with a larger proportion of patients with cardiomyopathy (33%). The indication in younger children was secondary prevention in all cases. Younger children may be under-represented in our study given the nature of the database as it is a predominantly adult cardiology database. CONCLUSIONS: In the past decade, ICD implantation has been performed in approximately 20 children per year in Japan, mostly for secondary prevention. There was no increase in the trend nor a change in age distribution.

Survival and Heart Failure Hospitalization in Patients With Cardiac Resynchronization Therapy With or Without a Defibrillator for Primary Prevention in Japan　- Analysis of the Japan Cardiac Device Treatment Registry Database.

BACKGROUND: Randomized control trials comparing the effectiveness of cardiac resynchronization therapy devices, with (CRT-D) or without (CRT-P) a defibrillator, are scarce in heart failure patients with no prior sustained ventricular tachyarrhythmias.Methods and Results:The Japan Cardiac Device Treatment Registry (JCDTR) has data for 2714 CRT-D and 555 CRT-P recipients for primary prevention with an implantation date between January 2011 and August 2015. Of these patients, follow-up data were available for 717. Over the mean follow-up period of 21 months, Kaplan-Meier curves of survival free of combined events for all-cause death or heart failure hospitalization (whichever came first) diverged between the CRT-D (n=620) and CRT-P (n=97) groups with a rate of 22% vs. 42%, respectively, at 24 months (P=0.0011). However, this apparent benefit of CRT-D over CRT-P was no longer significant after adjustment for covariates. With regard to mortality, including heart failure death or sudden cardiac death, there was no significant difference between the 2 groups. CONCLUSIONS: In patients without sustained ventricular tachyarrhythmias enrolled in the JCDTR, there was no significant difference in mortality between the CRT-D and CRT-P groups, despite a lower trend in CRT-D recipients. This study was limited by large clinical and demographic differences between the 2 groups.

[Surgical treatment of unroofed coronary sinus coexisting with paroxysmal atrial fibrillation; diagnosis by multidetector computed tomography; report of a case].

We experienced a rare case of an unroofed coronary sinus without a persistent left superior vena cava. A 55-year-old man, who was diagnosed with cerebral infarction, presented with suspected atrial septal defect (ASD) coexisting with paroxysmal atrial fibrillation. Before the operation, we diagnosed this case as coronary sinus ASD by contrast-enhanced coronary computed tomography (CT). There was a 20 mm segment of abnormal communication between the base of the left atrium and the roof of the coronary sinus. We repaired the defect by simple direct closure from the left atrium side, so that the coronary veins drained into the right atrium. The postoperative course was uneventful. Imaging played a crucial role in the diagnosis. Coronary CT angiography is well suited to help identify asymptomatic congenital heart disease.

Multicenter prospective observational study to clarify the current status and clinical outcome in Japanese patients who have an indication for implantable cardioverter defibrillator (ICD) or wearable cardioverter defibrillator (WCD) (TRANSITION JAPAN-ICD/WCD study): Rationale and design of a prospective, multicenter, observational, comparative study.

Background: Despite the positive impact of implantable cardioverter defibrillators (ICDs) and wearable cardioverter defibrillators (WCDs) on prognosis, their implantation is often withheld especially in Japanese heart failure patients with reduced left ventricular ejection fraction (HFrEF) who have not experienced ventricular tachycardia (VT) or ventricular fibrillation (VF) for uncertain reasons. Recent advancements in heart failure (HF) medications have significantly improved the prognosis for HFrEF. Given this context, a critical reassessment of the treatment and prognosis of ICDs and WCDs is essential, as it has the potential to reshape awareness and treatment strategies for these patients. Methods: We are initiating a prospective multicenter observational study for HFrEF patients eligible for ICD in primary and secondary prevention, and WCD, regardless of device use, including all consenting patients. Study subjects are to be enrolled from 31 participant hospitals located throughout Japan from April 1, 2023, to December 31, 2024, and each will be followed up for 1 year or more. The planned sample size is 651 cases. The primary endpoint is the rate of cardiac implantable electronic device implementation. Other endpoints include the incidence of VT/VF and sudden death, all-cause mortality, and HF hospitalization, other events. We will collect clinical background information plus each patient's symptoms, Clinical Frailty Scale score, laboratory test results, echocardiographic and electrocardiographic parameters, and serial changes will also be secondary endpoints. Results: Not applicable. Conclusion: This study offers invaluable insights into understanding the role of ICD/WCD in Japanese HF patients in the new era of HF medication.

The impact of geriatric nutritional risk index on one-year outcomes in hospitalized elderly patients with heart failure.

Background: Strategies that accurately predict outcomes in elderly heart failure (HF) patients have not been sufficiently established. In previous reports, nutritional status, ability to perform activities of daily living (ADL), and lower limb muscle strength are known prognostic factors associated with cardiac rehabilitation (CR). In the present study, we investigated which CR factors can accurately predict one-year outcomes in elderly patients with HF among the above factors. Methods: Hospitalized patients with HF over 65 years of age from January 2016 to January 2022 were retrospectively enrolled in the Yamaguchi Prefectural Grand Medical (YPGM) Center. They were consequently recruited to this single-center retrospective cohort study. Nutritional status, ADL, and lower limb muscle strength were assessed by geriatric nutritional risk index (GNRI), Barthel index (BI), and short physical performance battery (SPPB) at discharge, respectively. One year after discharge, the primary and secondary outcomes were evaluated by all-cause death or HF readmission and major adverse cardiac and cerebrovascular events (MACCE), respectively. Results: Overall, 1,078 HF patients were admitted to YPGM Center. Of those, 839 (median age 84.0, 52% female) met the study criteria. During the follow-up of 228.0 days, 72 patients reached all-cause death (8%), 215 experienced HF readmission (23%), and 267 reached MACCE (30%: 25 HF death, six cardiac death, and 13 strokes). A multivariate Cox proportional hazard regression analysis revealed that the GNRI predicted the primary outcome (Hazard ratio [HR]: 0.957; 95% confidence interval [CI]: 0.934-0.980; p < 0.001) and the secondary outcome (HR: 0.963; 95%CI: 0.940-0.986; p = 0.002). Furthermore, a multiple logistic regression model using the GNRI most accurately predicted the primary and secondary outcomes compared to those with the SPPB or BI models. Conclusion: A nutrition status model using GNRI provided a better predictive value than ADL ability or lower limb muscle strength. It should be recognized that HF patients with a low GNRI at discharge may have a poor prognosis at one year.

Characteristics of induced ventricular fibrillation cycle length in symptomatic Brugada syndrome patients.

BACKGROUND: Limited information is available on the ventricular fibrillation (VF) spectrum in Brugada syndrome (BS) patients. We clarified differences in the VF cycle length (CL) using fast-Fourier transformation (FFT) analysis in symptomatic and asymptomatic BS patients. METHODS AND RESULTS: VF was induced by pacing from the right ventricular (RV) apex and/or RV outflow tract (RVOT) for >8s. A 4096-point FFT analysis of results from 28 male BS patients (51.1 ± 13.7 years old) was performed. Dominant frequency (DF) from phases 1 (4s) to 6 was obtained at 2-s intervals. The average DF from surface and intracardiac electrograms (ECG: DF(ECG); ICE: DF(ICE,), respectively) was compared between symptomatic and asymptomatic patients. Symptomatic patients had a significantly shorter effective refractory period at a CL of 600 ms at the RVOT than asymptomatic patients. DF(ECG) significantly increased with phase (5.64 ± 0.32 Hz in phase 1 to 6.16 ± 0.52 Hz in phase 6) and was significantly higher in symptomatic patients than in asymptomatic patients. DF(ICE) had the same characteristics as DF(ECG). CONCLUSIONS: Induced VF in BS patients can be characterized using FFT analysis. Our data support the hypothesis that symptomatic patients have a significantly shorter VF CL than asymptomatic patients.

Urinary 8-hydroxy-2'-deoxyguanosine as a novel biomarker for predicting cardiac events and evaluating the effectiveness of carvedilol treatment in patients with chronic systolic heart failure.

BACKGROUND: The authors recently reported that urinary 8-hydroxy-2'-deoxyguanosine (U8-OHdG) derived from cardiac tissue reflects clinical status and cardiac dysfunction severity in patients with chronic heart failure (CHF). The aim of the present study was to investigate whether U8-OHdG levels can accurately predict cardiac events in CHF patients and their response to ß-blocker treatment. METHODS AND RESULTS: Plasma brain natriuretic peptide (BNP) and U8-OHdG levels were measured in 186 consecutive CHF patients before discharge. Patients were then prospectively followed (median follow-up, 649 days) with endpoints of cardiac death or hospitalization due to progressive heart failure. From receiver operating characteristic curve analysis, cut-offs were 12.4ng/mg creatinine (Cr) for U8-OHdG and 207pg/ml for BNP. On multivariate Cox analysis, U8-OHdG and BNP were independent predictors of cardiac events. Patients were classified into 4 groups according to U8-OHdG and BNP cut-offs. The hazard ratio for cardiac events in patients with BNP ≥207pg/ml and U8-OHdG ≥12.4ng/mg Cr was 16.2 compared with approximately 4 for patients with only 1 indicator above its respective cut-off. Furthermore, carvedilol therapy was initiated in 30 CHF patients. In responders (≥10% increase in left ventricular ejection fraction [LVEF] or ≥1 class decrease in New York Heart Association [NYHA] class), U8-OHdG levels decreased significantly along with improved NYHA class, LVEF, and BNP levels after treatment. CONCLUSIONS: U8-OHdG may be a useful biomarker for predicting cardiac events and evaluating ß-blocker therapy effectiveness in CHF patients.

Corrigendum: Malnutrition and Frailty Are Critical Determinants of 6-Month Outcome in Hospitalized Elderly Patients With Heart Failure Harboring Surgically Untreated Functional Mitral Regurgitation.

[This corrects the article DOI: 10.3389/fcvm.2021.764528.].

Impact of Atrial Tachyarrhythmia Recurrence on the Development of Long-Term Adverse Clinical Events Following Catheter Ablation in Patients With Atrial Fibrillation With Systolic Impairment: A Single-Center Observational Study.

Background Catheter ablation can improve long-term prognosis of patients with atrial fibrillation with systolic impairment. However, atrial tachyarrhythmia (ATA) recurrence increases during long-term follow-up. We aimed to investigate the impact of ATA recurrence on the development of long-term adverse clinical events following catheter ablation for atrial fibrillation and to identify predictors for the development of adverse clinical events. Methods and Results This single-center observational study included 75 patients with systolic impairment (left ventricular ejection fraction <50%) who underwent the first catheter ablation procedure for atrial fibrillation at our institution (median follow-up period: 3.5 [range: 2.4-4.7] years). We compared the cumulative incidence of adverse clinical events (all-cause death, heart failure hospitalization, stroke, or acute myocardial infarction) between the groups with and without ATA recurrence following the first and last procedures. Multivariable analyses were performed to identify predictors for developing adverse clinical events. Twenty-one patients (28%) developed adverse clinical events at a median of 2.2 (range: 0.64-2.8) years following the first procedure. The proportion of freedom from adverse clinical events following the first procedure was significantly lower in the ATA recurrence group than in the nonrecurrence group (41% [n=40] versus 95% [n=35], P<0.0005); the proportion following the last procedure also showed a similar tendency (35% [n=26] versus 57% [n=49], P<0.0001). ATA recurrence emerged as an independent predictor for adverse clinical events following both procedures after multivariable adjustment. Conclusions ATA recurrence following catheter ablation procedure could predict adverse clinical events in patients with atrial fibrillation with systolic impairment.

The Differential Prognostic Impact of Long-Duration Atrial High-Rate Episodes Detected by Cardiac Implantable Electronic Devices between Patients with and without a History of Atrial Fibrillation.

Long-duration atrial high-rate episodes (AHREs) monitored using cardiac implantable electronic devices (CIEDs) can predict long-term major adverse cardiovascular events (MACEs). This study aimed to compare the impact of long-duration AHRE on MACE development between patients with and without a history of atrial fibrillation (AF). This single-center observational study included 132 CIED-implanted patients with AHREs detected via remote monitoring. The population was dichotomized into groups: with (n = 69) and without (n = 63) AF. In each group, cumulative incidences of MACEs comprising all-cause deaths, heart failure hospitalizations, strokes, and acute coronary syndromes were compared between patients with AHRE durations of ≥24 h and <24 h. Multivariate analysis was performed to identify predictors of MACEs among patients without AF. MACE incidence was significantly higher in patients with AHRE ≥24 h than in those with <24 h in the group without AF (92% vs. 30%, p = 0.005). MACE incidence did not significantly differ between AHRE ≥24 h and <24 h in the group with AF (54% vs. 26%, p = 0.44). After a multivariate adjustment, AHRE duration of ≥24 h emerged as the only independent predictor of MACEs among patients without AF (p = 0.03). In conclusion, a long-duration AHRE was prognostic in patients without a history of AF but not in patients with a history of AHREs.

Long-term events following catheter-ablation for atrial fibrillation in heart failure with preserved ejection fraction.

AIMS: Data regarding prognostic events following catheter ablation (CA) for atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) are scarce. We conducted this study to compare the incidence of major adverse clinical events (MACE) following CA for AF between patients with HFpEF and those with systolic heart failure (HF). METHODS AND RESULTS: This single-centre observational study included 142 patients with HF who underwent CA for AF (median follow-up: 4.0 [2.6, 6.3] years). The patients were grouped based on the presence of HFpEF (n = 84) and systolic HF (left ventricular ejection fraction <50%, n = 58). We compared the cumulative incidence and incidence rate of MACE, comprising all-cause death, unplanned cardiovascular hospitalization (CVH), and HF hospitalization (HFH) between both groups and the number of HFH before and after CA in each group. Multivariate analysis was performed to identify the predictors of MACE in patients with HFpEF. The incidence of MACE was comparable between the groups (following the first procedure: HFpEF: 23%, 4.7/100 person-years, vs. systolic HF: 28%, 6.6/100 person-years, P = 0.18; last procedure: 20%, 4.8/100 person-years, vs. 24%, 6.9/100 person-years, P = 0.21). Although the incidence of HFH was lower in patients with HFpEF than in those with systolic HF (first procedure: 14%, 2.9/100 person-years, vs. 24%, 5.7/100 person-years, P = 0.07; last procedure: 11%, 2.5/100 person-years, vs. 24%, 6.9/100 person-years, P = 0.01), the incidence of CVH was higher (first procedure: 8%, 1.7/100 person-years, vs. 5%, 1.2/100 person-years, P = 0.74; last procedure: 6%, 1.4/100 person-years, vs. 2%, 0.5/100 person-years, P = 0.4). The number of HFH significantly decreased in both groups after CA (HFpEF: 1 hospitalization [the first and third quartiles: 0, 1] in pre-CA, vs. 0 hospitalizations [0, 0] in post-CA, P < 0.0001; systolic HF: 1 hospitalization [0, 1], vs. 0 hospitalizations [0, 0], P < 0.005). The proportion of HFH among total clinical events was significantly smaller in patients with HFpEF than in those with systolic HF (following the first procedure: 56% vs. 88%, P < 0.005; last procedure: 52% vs. 92%, P < 0.005). CONCLUSIONS: CA for AF could be beneficial for patients with HFpEF, similar to those with systolic HF. However, clinical events other than HFH should be considered cautiously in such patients.

Right ventricular dysfunction in patients with Brugada-like electrocardiography: a two dimensional strain imaging study.

BACKGROUND: Sodium channel blockers augment ST-segment elevation in the right precordial leads in patients undergoing Brugada-type electrocardiography (ECG). However, their effect on echocardiographic features is not known. We address this by assessing global and regional ventricular function using conventional Doppler and two- dimensional (2D) speckle tracking techniques. METHODS: Thirty-one patients with Brugada-type ECG were studied. A pure sodium channel blocker, pilsicainide, was used to provoke an ECG response. The percentage longitudinal systolic myocardial strain at the base of both the right ventricular (RV) free wall and the interventricular septum wall was measured using 2D speckle tracking. Left ventricular (LV) and RV myocardial performance (TEI) indices were also measured. RESULTS: The pilsicainide challenge provoked a positive ECG response in 13 patients (inducible group). In the inducible group, longitudinal strain was significantly reduced only at the RV (-27.3 ± 5.4% vs -22.1 ± 3.6%, P < 0.01), and both RV and LV TEI indices increased (RV: 0.19 ± 0.09 vs 0.27 ± 0.11, P < 0.05; LV: 0.30 ± 0.10 vs 0.45 ± 0.10, P < 0.01) after pilsicainide administration. CONCLUSIONS: Temporal and spatial analysis using the TEI index and 2D strain imaging revealed the deterioration of global ventricular function associated with conduction disturbance and RV regional function in patients with Brugada-type ECG and coved type ST elevation due to administration of a sodium channel blocker.

[Ball thrombus induced by hibernating myocardium in the left ventricle; report of a case].

An 80-year-old man was admitted to our hospital for examination of a ball thrombus incidentally found in the left ventricle (LV). Coronary angiogram revealed severe triple vessel disease and LV dysfunction. Although LV wall motion in the septum and the apex was akinetic, there were no signs of myocardial infarction. It was diagnosed as an acute LV ball thrombus with hibernating myocardium due to ischemia of the left anterior descending coronary artery. Emergency coronary artery bypass grafting (CABG) and excision of the thrombus were performed. Two weeks after surgery, LV function improved and the patient was discharged from the hospital without any complication. A LV ball thrombus without myocardial infarction is rare, and thought to be caused by hibernating myocardium.

Malnutrition and Frailty Are Critical Determinants of 6-Month Outcome in Hospitalized Elderly Patients With Heart Failure Harboring Surgically Untreated Functional Mitral Regurgitation.

Background: Hospitalized patients with acute decompensated heart failure (ADHF) frequently exhibit aggravating mitral regurgitation (MR). Those patients do not always undergo surgical mitral valve repair, but particularly in the elderly, they are often treated by conservative medical therapy. This study was aimed to investigate factors affecting 6-month outcomes in hospitalized patients with heart failure (HF) harboring surgically untreated MR. Methods: We screened the presence of MR in hospitalized patients with HF between September 2017 and May 2020 in the Yamaguchi Prefectural Grand Medical (YPGM) center. At the time of discharge of these patients, individuals with surgically unoperated MR, including primary and secondary origin, were consequently recruited to this single-center prospective cohort study. The patients with severe MR who undergo surgical mitral valve treatment were not included in this study. The primary endpoint was all-cause readmission or all-cause death and the secondary endpoint was HF-related endpoint at 6 months after discharge. The Cox proportional hazard regression analyses were employed to assess the predictors for the composite endpoint. Results: Overall, 489 patients with ADHF were admitted to the YPGM center. Of those, 146 patients (30% of total patients with HF) (median age 83.5 years, 69 men) were identified as harboring grade II MR or greater. Consequently, all the recruited patients were diagnosed as functional MR. During a median follow-up of 186.0 days, a total of 55 patients (38%) reached the primary or secondary endpoints (HF death and readmission in 31 patients, other in 24 patients). As a result of multivariate analysis, geriatric nutritional risk index [hazard ratio (HR) = 0.932; 95% CI = 0.887-0.979, p = 0.005], age (HR = 1.058; 95% CI = 1.006-1.112, p = 0.027), and left ventricular ejection fraction (HR = 0.971; 95% CI = 0.945-0.997, p = 0.030) were independent predictors of all-cause death or all-cause admission. Body mass index (HR = 0.793; 95% CI = 0.614-0.890, p = 0.001) and ischemic heart disease etiology (HR = 2.732; 95% CI = 1.056-7.067, p = 0.038) were also independent predictors of the HF-related endpoints. Conclusion: Malnutrition and underweight were substantial predictors of adverse outcomes in elderly patients with HF harboring surgically untreated moderate-to-severe functional MR.

An impact of superior vena cava isolation in non-paroxysmal atrial fibrillation patients with low voltage areas.

BACKGROUND: This study aimed to investigate the correlation between left atrial low-voltage areas (LVAs) and an arrhythmogenic superior vena cava (SVC) and the impact on the efficacy of an empiric SVC isolation (SVCI) along with a pulmonary vein isolation (PVI) of non-paroxysmal atrial fibrillation (non-PAF) with or without LVAs. METHODS: We retrospectively enrolled 153 consecutive patients with non-PAF who underwent a PVI alone (n = 51) or empiric PVI plus an SVCI (n = 102). Left atrial voltage maps were constructed during sinus rhythm to identify the LVAs (<0.5 mV). An arrhythmogenic SVC was defined as firing from the SVC and an SVC associated with the maintenance of AF-like rapid SVC activity. RESULTS: An arrhythmogenic SVC and LVAs were identified in 28% and 65% of patients with a PVI alone and 36% and 73% of patients with a PVI plus SVCI, respectively (P = .275 and P = .353). In the multivariate analysis a female gender, higher pulmonary artery systolic pressure (PAPs), and arrhythmogenic SVC were associated with the presence of LVAs. In the PVI plus SVCI strategy, there was no significant difference in the atrial tachyarrhythmia/AF-free survival between the patients with and without LVAs after initial and multiple sessions (50% vs. 61%; P = .386, 73% vs. 79%; P = .530), however, differences were observed in the PVI alone group (27% vs. 61%; P = .018, 49% vs. 78%; P = .046). CONCLUSIONS: The presence of LVAs was associated with an arrhythmogenic SVC. An SVCI may have the potential to compensate for an impaired outcome after a PVI in non-PAF patients with LVAs.

Spinal cord stimulation improves ventricular function and reduces ventricular arrhythmias in a canine postinfarction heart failure model.

BACKGROUND: Spinal cord stimulation (SCS) reduces the incidence of ventricular tachyarrhythmias in experimental models. This study investigated the effects of long-term SCS on ventricular function in a postinfarction canine heart failure model. METHODS AND RESULTS: In stage 1, dogs underwent implantable cardioverter-defibrillator implantation and embolization of the left anterior descending artery followed by right ventricular pacing (240 ppm) for 3 weeks to produce heart failure. In stage 2, 28 surviving animals were assigned to the SCS (delivered at the T4/T5 spinal region for 2 hours 3 times a day), medicine (MED; carvedilol therapy at 12.5 mg PO BID), or control (CTRL; no therapy) group for the initial phase 1 study. In a subsequent phase 2 study, 32 stage 1 survivors were equally randomized to the SCS, MEDS (carvedilol plus ramipril 2.5 mg PO QD), SCS plus MEDS (concurrent therapy), or CTRL group. Animals were monitored for 5 weeks (phase 1) or 10 weeks (phase 2). In stage 3, all phase 1 animals underwent circumflex artery balloon occlusion for 1 hour. In the SCS group, left ventricular ejection fraction was 65+/-5% at baseline, 17+/-3% at the end of stage 1, and 47+/-7% at the end of stage 2. In the MED group, left ventricular ejection fraction was 61+/-4% at baseline, 18+/-3% at the end of stage 1, and 34+/-4% at the end of stage 2. In the CTRL group, left ventricular ejection fraction was 64+/-5% at baseline, 19+/-5% at the end of stage 1, and 28+/-3% at the end of stage 2. Left ventricular ejection fraction was significantly improved in the SCS compared with the MED and CTRL groups (P<0.001 for both). The mean number of spontaneous nonsustained ventricular tachyarrhythmias during stage 2 and the occurrence of ischemic ventricular tachyarrhythmias during stage 3 also were significantly decreased in the SCS (27+/-17 and 27%, respectively; P<0.03) and MED (58+/-42 and 33%; P<0.05) versus CTRL (88+/-52 and 76%) group. After 10 weeks in the phase 2 studies, the greatest recovery in ejection fraction was noted in the SCS (52+/-5%) and SCS+MEDS (46+/-4%) groups compared with the MEDS (38+/-2%) and CTRL (31+/-4%) groups. CONCLUSIONS: SCS significantly improved cardiac contractile function and decreased ventricular arrhythmias in canine heart failure.

G790del mutation in DSC2 alone is insufficient to develop the pathogenesis of ARVC in a mouse model.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease that causes heart failure and/or sudden cardiac death. Several desmosomal genes (DSC2, PKG, PKP2, DSP, and RyR2) are thought to be the causative gene involved in ARVC. Out of them, DSC2 mutations account for 2% of ARVC genetic abnormalities. This study aimed to clarify the effect of G790del mutation in DSC2 on the arrhythmogenic mechanism and cardiac function in a mouse model. RESULT: Neither the heterozygous +/G790del nor homozygous G790del/G790del mice showed structural and functional defects in the right ventricle (RV) or lethal arrhythmia. The homozygous G790del/G790del 6-month-old mice slightly showed left ventricular (LV) dysfunction. Cell shortening decreased with prolongation of intracellular Ca2+ transient in cardiomyocytes isolated from the homozygous G790del/G790del mice, and spontaneous Ca2+ transients were frequently observed in response to isoproterenol. CONCLUSIONS: G790del mutation in DSC2 was not relevant to the pathogenesis of ARVC, but showed a slight contractile dysfunction and Ca2+ dysregulation in the LV.