Ventricular arrhythmias and sudden death in adults after a Mustard operation for transposition of the great arteries

AIMS: To examine the prevalence of sustained ventricular tachycardia (VT) and sudden death (SD) in adults with atrial repair of transposition of the great arteries (TGA) and to determine associated risk factors. METHODS AND RESULTS: In a single-centre review, we studied the outcome of 149 adults (mean age 28 +/- 7 years) who had undergone a Mustard operation for TGA. During a mean follow-up of 9 +/- 6 years, sustained VT and/or SD occurred in 9% (13/149) of the cohort. Sustained VT/SD was more likely to occur in patients with associated anatomic lesions [hazard ratio (HR) 4.9, 95% CI 1.5-16.0], with NYHA class >or=III (HR 9.8, 95% CI 3.0-31.6) and with an impaired subaortic right ventricular (RV) ejection fraction (EF) (HR 2.2, 95% CI 1.2-4.0 per 10% decrease in EF). There was an inverse correlation between the RV-EF and both age and QRS duration. Patients with a QRS duration >or=140 ms were at highest risk of sustained VT/SD (HR 13.6, 95% CI 2.9-63.4). Atrial tachyarrhythmia was detected in 66 (44%) patients, but was not a statistically significant predictor of sustained VT/SD in our adult population (HR 2.7, 95% CI 0.6-13.0). CONCLUSION: Sustained VT/SD in adults after a Mustard operation for TGA are more common than previously described. Age, systemic ventricular function, and QRS duration are interrelated and are associated with VT/SD. A QRS duration >or=140 ms helps to identify the high risk patient.

Esophagus imaging for catheter ablation of atrial fibrillation: comparison of two methods with showing of esophageal movement

This study aims to evaluate whether visualization and integration of the computed tomography (CT) scan of the left atrium (LA) and the esophagus into the three-dimensional (3D) electroanatomical map the day before ablation is accurate compared with integration of an esophagus tag into the electroanatomic LA map visualizing the anatomic relationship during the radiofrequency ablation or whether esophagus movement prohibits esophagus visualization the day before ablation.

Different effects of cyclosporin A on bone remodeling in young and adult rats

Reported effects of cyclosporin A (Sandimmun, CsA) on bone have been both contradictory and controversial. Thus, stimulation of new bone formation as well as increased mineral and matrix resorption have been observed. To investigate the response of basal mineral and matrix turnover to CsA treatment at different stages of skeletal development, comparative experiments were conducted in young growing female rats and in adults. Fifty-six young animals (study A) and 40 adults (study B) received orally either the carrier substance or 5, 15, and 30 mg/kg CsA for 30 days. The following parameters were measured: (a) total skeletal mineral content by dual energy X-ray absorptiometry (DEXA) on days 1 and 30; (b) tibial trabecular volume at day 30; (c) serum osteocalcin at 5-day intervals; (d) urinary deoxypyridinoline (Dpd) excretion (days 1, 15, and 30); and (e) plasma levels of CsA. Results can be summarized as follows: in young rats (study A), total skeletal mineral was not modified by the 5- and 15-mg/kg doses of CsA, whereas 30 mg/kg induced a significant decrease (-15%, p < 0.01). This parameter was not significantly modified in adult animals (study B) subjected to the same doses. The administration of 5 mg/kg CsA did not alter tibial trabecular volume in young rats, but 15 and 30 mg/kg significantly lowered this parameter (-16.3%, p < 0.02, and -42%, p < 0.001, respectively). In adult rats, tibial trabecular volume remained unchanged with the exception of the group receiving 30 mg/kg which exhibited significantly lower values (-28%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

The bovine dilated cardiomyopathy locus maps to a 1.0-Mb interval on chromosome 18

Cardiomyopathies are myocardial diseases that lead to cardiac dysfunction, heart failure, arrhythmia, and sudden death. In human medicine, cardiomyopathies frequently warrant heart transplantation in children and adults. Bovine dilated cardiomyopathy (BDCMP) is a heart muscle disorder that has been observed during the last 30 years in cattle of Holstein-Friesian origin. In Switzerland BDCMP affects Swiss Fleckvieh and Red Holstein breeds. BDCMP is characterized by a cardiac enlargement with ventricular remodeling and chamber dilatation. The common symptoms in affected animals are subacute subcutaneous edema, congestion of the jugular veins, and tachycardia with gallop rhythm. A cardiomegaly with dilatation and hypertrophy of all heart chambers, myocardial degeneration, and fibrosis are typical postmortem findings. It was shown that all BDCMP cases reported worldwide traced back to a red factor-carrying Holstein-Friesian bull, ABC Reflection Sovereign. An autosomal recessive mode of inheritance was proposed for BDCMP. Recently, the disease locus was mapped to a 6.7-Mb interval MSBDCMP06-BMS2785 on bovine Chr 18 (BTA18). In the present study the BDCMP locus was fine mapped by using a combined strategy of homozygosity mapping and association study. A BAC contig of 2.9 Mb encompassing the crucial interval was constructed to establish the correct marker order on BTA18. We show that the disease locus is located in a gene-rich interval of 1.0 Mb and is flanked by the microsatellite markers DIK3006 and MSBDCMP51.

Graft remodeling during growth following anterior cruciate ligament reconstruction in skeletally immature sheep

INTRODUCTION: Ruptures of the anterior cruciate ligament are being diagnosed with increasing frequency in skeletally immature individuals. It was our aim to investigate the graft remodelling process following an autologous, transphyseal reconstruction of the anterior cruciate ligament (ACL) in skeletally immature sheep. We hypothesized that the ligamentisation process in immature sheep is quicker and more complete when compared to adult sheep. MATERIALS AND METHODS: Skeletally immature sheep with an age of 4 months underwent a fully transphyseal ACL reconstruction using an autologous tendon. The animals were subsequently sacrificed at 3, 6, 12 and 24 weeks following surgery. Each group was characterised histomorphometrically, by immunostaining (VEGF, SMA), by transmission electron microscopy (TEM) and biomechanically (UFS Roboter). RESULTS: The histomorphometric analysis and presence of VEGF and SMA positive cells demonstrated a rapid return to a ligament like structure. The biomechanical analysis revealed an anteroposterior translation that was still increased even 6 months following surgery. CONCLUSION: As in adult sheep models, the remodeling of a soft tissue graft used for ACL reconstruction results in a biomechanically inferior substitute. However, the immature tissue seems to remodel faster and more complete when compared to adults.

Dynamic patterns of ventricular remodeling and apoptosis in hearts unloaded by heterotopic transplantation

BACKGROUND Mechanical unloading of failing hearts can trigger functional recovery but results in progressive atrophy and possibly detrimental adaptation. In an unbiased approach, we examined the dynamic effects of unloading duration on molecular markers indicative of myocardial damage, hypothesizing that potential recovery may be improved by optimized unloading time. METHODS Heterotopically transplanted normal rat hearts were harvested at 3, 8, 15, 30, and 60 days. Forty-seven genes were analyzed using TaqMan-based microarray, Western blot, and immunohistochemistry. RESULTS In parallel with marked atrophy (22% to 64% volume loss at 3 respectively 60 days), expression of myosin heavy-chain isoforms (MHC-α/-β) was characteristically switched in a time-dependent manner. Genes involved in tissue remodeling (FGF-2, CTGF, TGFb, IGF-1) were increasingly upregulated with duration of unloading. A distinct pattern was observed for genes involved in generation of contractile force; an indiscriminate early downregulation was followed by a new steady-state below normal. For pro-apoptotic transcripts bax, bnip-3, and cCasp-6 and -9 mRNA levels demonstrated a slight increase up to 30 days unloading with pronunciation at 60 days. Findings regarding cell death were confirmed on the protein level. Proteasome activity indicated early increase of protein degradation but decreased below baseline in unloaded hearts at 60 days. CONCLUSIONS We identified incrementally increased apoptosis after myocardial unloading of the normal rat heart, which is exacerbated at late time points (60 days) and inversely related to loss of myocardial mass. Our findings suggest an irreversible detrimental effect of long-term unloading on myocardium that may be precluded by partial reloading and amenable to molecular therapeutic intervention.

Amplatzer left atrial appendage occlusion: single center 10-year experience

OBJECTIVES To report a 10-year single center experience with Amplatzer devices for left atrial appendage (LAA) occlusion. BACKGROUND Intermediate-term outcome data following LAA occlusion are scarce. METHODS Short- and intermediate-term outcomes of patients who underwent LAA occlusion were assessed. All procedures were performed under local aesthesia without transesophageal echocardiography. Patients were discharged on acetylsalicylic acid and clopidogrel for 1-6 months. RESULTS LAA occlusion was attempted in 152 patients (105 males, age 72 ± 10 years, CHA2 DS2 -Vasc-score 3.4 ± 1.7, HAS-BLED-score 2.4 ± 1.2). Nondedicated devices were used in 32 patients (21%, ND group) and dedicated Amplatzer Cardiac Plugs were used in 120 patients (79%, ACP group). A patent foramen ovale or atrial septal defect was used for left atrial access and closed at the end of LAA occlusion in 40 patients. The short-term safety endpoints (procedural complications, bleeds) occurred in 15 (9.8%) and the efficacy endpoints (death, stroke, systemic embolization) in 0 patients. Device embolization occurred more frequently in the ND as compared to the ACP group (5 patients or 12% vs. 2 patients or 2%). Mean intermediate-term follow up of the study population was 32 months (range 1-120). Late deaths occurred in 15 patients (5 cardiovascular, 7 noncardiac, 3 unexplained). Neurologic events occurred in 2, peripheral embolism in 1, and major bleeding in 4 patients. The composite efficacy and safety endpoint occurred in 7% and 12% of patients. CONCLUSION LAA closure may be a good alternative to oral anticoagulation. This hypothesis needs to be tested in a randomized clinical trial to ensure that all potential biases of this observational study are accounted for.

The optimal lead insertion depth for esophageal ECG recordings with respect to atrial signal quality

BACKGROUND Diagnosing supraventricular arrhythmias by conventional long-term ECG can be cumbersome because of poor p-waves. Esophageal long-term electrocardiography (eECG) has an excellent sensitivity for atrial signals and may overcome this limitation. However, the optimal lead insertion depth (OLID) is not known. METHODS We registered eECGs at different lead insertion depths in 27 patients and analyzed 199,716 atrial complexes with respect to signal amplitude and slope. Correlation and regression analyses were used to find a criterion for OLID. RESULTS Atrial signal amplitudes and slopes significantly depend on lead insertion depth. OLID correlates with body height (rSpearman=0.71) and can be estimated by OLID [cm]=0.25*body height[cm]-7cm. At this insertion depth, we recorded the largest esophageal atrial signal amplitudes (1.27±0.86mV), which were much larger compared to conventional surface lead II (0.19±0.10mV, p<0.0001). CONCLUSION The OLID depends on body height and can be calculated by a simple regression formula.

Amplatzer left atrial appendage occlusion through a patent foramen ovale

OBJECTIVES: To assess feasibility and outcomes of left atrial appendage (LAA) closure when using a patent foramen ovale (PFO) for left atrial access. Background: Because of the fear of entering the left atrium too high, using a PFO for left atrial access during LAA occlusion (LAAO) is generally discouraged. We report our single-center experience using a concomitant PFO for LAAO, thereby avoiding transseptal puncture. METHODS: LAAO was performed with local anesthesia and fluoroscopic guidance only (no echocardiography). The Amplatzer Cardiac Plug (ACP) was used in all patients. After LAAO, the PFO was closed at the same sitting, using an Amplatzer occluder through the ACP delivery sheath. Patients were discharged the same or the following day on dual antiplatelet therapy for 1-6 months, at which time a follow-up transesophageal echocardiogram (TEE) was performed. RESULTS: In 49 (96%) of 51 patients (35 males, age 70.9 ± 11.9 years), LAAO was successful using the PFO for left atrial access. In one patient, a long tunnel PFO precluded LAAO, which was performed via a more caudal transseptal puncture. In a second patient, a previously inserted ASD occluder precluded LAAO, which was abandoned because of pericardial bleeding. PFO closure was successful in all patients. Follow-up TEE was performed in 43 patients 138 ± 34 days after the procedure. It showed proper sitting of both devices in all patients. CONCLUSIONS: Using a PFO for LAAO had a high success rate and could be the default access in all patients with a PFO, potentially reducing procedural complications arising from transseptal puncture.

Endocardial Ablation to Eliminate Epicardial Arrhythmia Substrate in Scar-Related Ventricular Tachycardia

OBJECTIVES We evaluated the feasibility and safety of epicardial substrate elimination using endocardial radiofrequency (RF) delivery in patients with scar-related ventricular tachycardia (VT). BACKGROUND Epicardial RF delivery is limited by fat or associated with bleeding, extra-cardiac damages, coronary vessels and phrenic nerve injury. Alternative ablation approaches may be desirable. METHODS Forty-six patients (18 ischemic cardiomyopathy [ICM], 13 non-ischemic dilated cardiomyopathy [NICM], 15 arrhythmogenic right ventricular cardiomyopathy [ARVC]) with sustained VT underwent combined endo- and epicardial mapping. All patients received endocardial ablation targeting local abnormal ventricular activities in the endocardium (Endo-LAVA) and epicardium (Epi-LAVA), followed by epicardial ablation if needed. RESULTS From a total of 173 endocardial ablations targeting Epi-LAVA at the facing site, 48 (28%) applications (ICM: 20/71 [28%], NICM: 3/39 [8%], ARVC: 25/63 [40%]) successfully eliminated the Epi-LAVA. Presence of Endo-LAVA, most delayed and low bipolar amplitude of Epi-LAVA, low unipolar amplitude in the facing endocardium, and Epi-LAVA within a wall thinning area at CT scan were associated with successful ablation. Endocardial ablation could abolish all Epi-LAVA in 4 ICM and 2 ARVC patients, whereas all patients with NICM required epicardial ablation. Endocardial ablation was able to eliminate Epi-LAVA at least partially in 15 (83%) ICM, 2 (13%) NICM, and 11 (73%) ARVC patients, contributing to a potential reduction in epicardial RF applications. Pericardial bleeding occurred in 4 patients with epicardial ablation. CONCLUSIONS Elimination of Epi-LAVA using endocardial RF delivery is feasible and may be used first to reduce the risk of epicardial ablation.

Different Prognostic Value of Functional Right Ventricular Parameters in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

BACKGROUND -The value of standard two-dimensional transthoracic echocardiographic (TTE) parameters for risk stratification in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is controversial. METHODS AND RESULTS -We investigated the impact of right ventricular fractional area change (FAC) and tricuspid annulus plane systolic excursion (TAPSE) for prediction of major adverse cardiovascular events (MACE) defined as the occurrence of cardiac death, heart transplantation, survived sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia or arrhythmogenic syncope. Among 70 patients who fulfilled the 2010 ARVC/D Task Force Criteria and underwent baseline TTE, 37 (53%) patients experienced a MACE during a median follow-up period of 5.3 (IQR 1.8-9.8) years. Average values for FAC, TAPSE, and TAPSE indexed to body surface area (BSA) decreased over time (p=0.03 for FAC, p=0.03 for TAPSE and p=0.01 for TAPSE/BSA, each vs. baseline). In contrast, median right ventricular end-diastolic area (RVEDA) increased (p=0.001 vs. baseline). Based on the results of Kaplan-Meier estimates, the time between baseline TTE and experiencing MACE was significantly shorter for patients with FAC <23% (p<0.001), TAPSE <17mm (p=0.02) or right atrial (RA) short axis/BSA ≥25mm/m(2) (p=0.04) at baseline. A reduced FAC constituted the strongest predictor of MACE (hazard ratio 1.08 per 1% decrease; 95% confidence interval 1.04-1.12; p<0.001) on bivariable analysis. CONCLUSIONS -This long-term observational study indicates that TAPSE and dilation of right-sided cardiac chambers are associated with an increased risk for MACE in ARVC/D patients with advanced disease and a high risk for adverse events. However, FAC is the strongest echocardiographic predictor of adverse outcome in these patients. Our data advocate a role for TTE in risk stratification in patients with ARVC/D, although our results may not be generalizable to lower risk ARVC/D cohorts.

Usefulness of inducible ventricular tachycardia to predict long-term adverse outcomes in arrhythmogenic right ventricular cardiomyopathy

The role of the electrophysiologic (EP) study for risk stratification in patients with arrhythmogenic right ventricular cardiomyopathy is controversial. We investigated the role of inducible sustained monomorphic ventricular tachycardia (SMVT) for the prediction of an adverse outcome (AO), defined as the occurrence of cardiac death, heart transplantation, sudden cardiac death, ventricular fibrillation, ventricular tachycardia with hemodynamic compromise or syncope. Of 62 patients who fulfilled the 2010 Arrhythmogenic Right Ventricular Cardiomyopathy Task Force criteria and underwent an EP study, 30 (48%) experienced an adverse outcome during a median follow-up of 9.8 years. SMVT was inducible in 34 patients (55%), 22 (65%) of whom had an adverse outcome. In contrast, in 28 patients without inducible SMVT, 8 (29%) had an adverse outcome. Kaplan-Meier analysis showed an event-free survival benefit for patients without inducible SMVT (log-rank p = 0.008) with a cumulative survival free of an adverse outcome of 72% (95% confidence interval [CI] 56% to 92%) in the group without inducible SMVT compared to 26% (95% CI 14% to 50%) in the other group after 10 years. The inducibility of SMVT during the EP study (hazard ratio [HR] 2.99, 95% CI 1.23 to 7.27), nonadherence (HR 2.74, 95% CI 1.3 to 5.77), and heart failure New York Heart Association functional class II and III (HR 2.25, 95% CI 1.04 to 4.87) were associated with an adverse outcome on univariate Cox regression analysis. The inducibility of SMVT (HR 2.52, 95% CI 1.03 to 6.16, p = 0.043) and nonadherence (HR 2.34, 95% CI 1.1 to 4.99, p = 0.028) remained as significant predictors on multivariate analysis. This long-term observational data suggest that SMVT inducibility during EP study might predict an adverse outcome in patients with arrhythmogenic right ventricular cardiomyopathy, advocating a role for EP study in risk stratification.

Electrophysiologic characterization of local abnormal ventricular activities in postinfarction ventricular tachycardia with respect to their anatomic location.

BACKGROUND Local abnormal ventricular activities (LAVA) in patients with scar-related ventricular tachycardia (VT) may appear at any time during or after the far-field electrogram. Although they may be separated from the far-field signal by an isoelectric line and extend beyond the end of surface QRS, they may also appear fused or buried within the QRS. OBJECTIVE The purpose of this study was to characterize LAVA in postinfarction VT patients with respect to their anatomic locations. METHODS Thirty-one patients with postinfarction VT underwent mapping/ablation during sinus rhythm with a three-dimensional electroanatomic mapping system. From a total of 18,270 electrograms reviewed in all study subjects, 1104 LAVA (endocardium 839, epicardium 265) were identified and analyzed. RESULTS The interval from onset of QRS complex to ventricular electrogram (EGM onset) on the endocardium was significantly shorter than the epicardium (P < .001). EGM onset was shortest in the septal endocardium and longest in the inferior and lateral epicardium. There was a significant positive correlation between EGM onset and LAVA lateness as estimated by the interval from surface QRS onset to LAVA (r = 0.52, P < .001). LAVA were more frequently detected after the QRS complex in the epicardium (241/265 [91%]) than in the endocardium (551/839 [66%], P < .001). Only 43% of endocardial septal LAVA were detected after the QRS complex. CONCLUSION Lateness of LAVA is affected to a large extent by their locations. The chance of detecting late LAVA increases when electrogram onset is later. Substrate-based approach targeting delayed signals relative to the QRS complex may miss critical the arrhythmogenic substrate, particularly in the septum and other early-to-activate regions.