Utilization of 3D mapping systems in interventional electrophysiology and its impact on procedure time and fluoroscopy-Insights from the "Go for Zero Fluoroscopy" project.

AIM: The implementation of 3D mapping systems plays an important role in interventional electrophysiology (EP) in recent years. The aim of the present study was to evaluate use of 3D mapping systems regarding fluoroscopy and procedure duration. METHOD: In the "Go for Zero Fluoroscopy" project 25 European centers provided data of consecutive EP procedures. Data on use of 3D mapping systems as well as utilization of contact force catheters and multipolar mapping catheters were associated with fluoroscopy time, dose area product (DAP), and procedure duration. RESULT: A 3D mapping system was used in 966 (54%) cases. Use of 3D mapping for atrioventricular nodal reentry tachycardia (AVNRT) was associated with reduced fluoroscopy time (p < 0.001), DAP (p = 0.04) but increased procedure time (p = 0.029). Moreover, fluoroscopy time (p < 0.001) and DAP (p = 0.005) were significantly lower in the 3D mapping group in ablation of typical atrial flutter. However, the procedure time (p < 0.001) increased. Use of 3D mapping in the ablation of accessory pathway (AP) was associated with reduced fluoroscopy time (p < 0.001) and DAP (p < 0.001) with no significant increase in procedure time (p = 0.066). In the case of atrial fibrillation, a 3D mapping system was used in 485 patients (75.8%). Additional use of a contact force catheter was associated with lower fluoroscopy time (p < 0.001) and DAP (p < 0.001). Use of a multipolar mapping catheter was associated with lower fluoroscopy time (p = 0.002). The implementation of 3D mapping systems in the ablation of ventricular tachycardias resulted in a significant increase in the procedure time (p = 0.001) without significant differences regarding the DAP (p = 0.773) and fluoroscopy time (p = 0.249). CONCLUSION: Use of 3D mapping systems in ablation of supraventricular tachycardias is associated with lower radiation exposure. Nevertheless, the procedure time often increases, except in the case of ablation for AP. Use of contact force catheters and multipolar mapping catheters is associated with yet lower radiation exposure values. Prospective randomized studies are needed to further elucidate potential benefit of these technological tools.

Stereotactic radioablation for ventricular tachycardia.

Non-invasive stereotactic radioablation of ventricular tachycardia (VT) substrate has been proposed as a novel treatment modality for patients not eligible for catheter-based ablation or in whom this approach has failed. Initial clinical results are promising with good short-term efficacy in VT suppression and tolerable side effects. This article reviews the current clinical evidence for cardiac radioablation and gives an overview of important preclinical and translational results. Practical guidance is provided, and a cardiac radioablation planning and treatment workflow based on expert consensus and the authors' institutional experience is set out.

Eligibility for subcutaneous implantable cardioverter-defibrillator in adults with congenital heart disease.

AIMS: Patients with adult congenital heart disease (ACHD) carry an increased risk for sudden cardiac death. Implantable cardioverter-defibrillator (ICD) therapy may be challenging in these patients due to anatomical barriers, repeated cardiac surgery, or complicated transvenous access. Thus, the subcutaneous ICD (S-ICD) can be a promising alternative in this patient population. Patients with ACHD show significant electrocardiogram (ECG) abnormalities, which could affect S-ICD sensing because it depends on surface ECG. METHODS AND RESULTS: One hundred patients with ACHD were screened for S-ICD eligibility. Standard ECG-based screening test and automated S-ICD screening test were performed in all patients. Sixty-six patients (66%) were male. Underlying congenital heart disease (CHD) was mainly CHD of great complexity (71%) and moderate complexity (29%), including repaired tetralogy of Fallot (20%), which was the most common entity. Thirty-seven patients (37%) already had a pacemaker (23%) or ICD (14%) implanted. Automated screening test identified 83 patients (83%) eligible for S-ICD implantation in either left parasternal position (78%) or right parasternal position (75%). Absence of sinus rhythm, QRS duration, and a paced QRS complex were associated with S-ICD screening failure in univariate analysis. Receiver operating characteristic curve and multivariate analysis revealed a QRS duration ≥148 ms as the only independent predictor for S-ICD screening failure. CONCLUSIONS: Patients with ACHD show satisfactory eligibility rates (83%) for S-ICD implantation utilizing the automated screening test, including patients with CHD of high complexity. S-ICD therapy should be considered with caution in ACHD patients with a QRS duration ≥148 ms and/or need for ventricular pacing.

Inhibition of CaMKII Attenuates Progressing Disruption of Ca(2+) Homeostasis Upon Left Ventricular Assist Device Implantation in Human Heart Failure.

In heart failure, left ventricular assist device (LVAD) implantation is performed to ensure sufficient cardiac output. Whereas some patients are subsequently weaned from LVAD support, other patients still need heart transplantation. To elucidate underlying mechanisms, we assessed the arrhythmogenic SR-Ca(2+) leak at the time of LVAD implantation (HF-Im) and heart transplantation (HF-Tx) and evaluated the effects of CaMKII-inhibition. Human left-ventricular cardiomyocytes were isolated, paced at 1 Hz for 10 beats to ensure SR-Ca(2+) loading and scanned for diastolic Ca(2+) sparks (confocal microscopy). In HF-Im, the high diastolic spark frequency (CaSpF) of 0.76 ± 0.12 × 100 µm(-1) × s(-1) could be reduced to 0.48 ± 0.10 × 100 µm(-1) × s(-1) by CaMKII inhibition (AIP, 1 µM). The amplitude of Ca(2+) sparks, width, and length was not significantly altered. In sum, CaMKII inhibition yielded a clear tendency toward a reduction of the SR-Ca(2+) leak (n cells/patients = 76/6 vs. 108/6, P = 0.08). In HF-Tx, we detected an even higher CaSpF of 1.00 ± 0.10 100 µm(-1) × s(-1) and a higher SR-Ca(2+) leak compared with HF-Im (increase by 81 ± 33%, n cells/patients = 156/7 vs. 130/7, P < 0.05), which fits to the further decreased LV function. Here, CaMKII inhibition likewise reduced CaSpF (0.35 ± 0.09 100 µm(-1) × s(-1,) P = 0.06) and significantly reduced spark duration (n sparks/patients = 58/3 vs. 159/3, P < 0.05). Conclusively, the SR-Ca(2+) leak was reduced by 69 ± 12% in HF-Tx upon CaMKII inhibition (n cells/patients = 53/3 vs. 91/3, P < 0.05). These data show that the SR-Ca(2+) leak correlates with the development of LV function after LVAD implantation and may represent an important pathomechanism. The fact that CaMKII inhibition reduces the SR-Ca(2+) leak in HF-Tx suggests that CaMKII inhibition may be a promising option to beneficially influence clinical course after LVAD implantation.

Sex-dependent alterations of Ca2+ cycling in human cardiac hypertrophy and heart failure.

AIMS: Clinical studies have shown differences in the propensity for malignant ventricular arrhythmias between women and men suffering from cardiomyopathies and heart failure (HF). This is clinically relevant as it impacts therapies like prophylactic implantable cardioverter-defibrillator implantation but the pathomechanisms are unknown. As an increased sarcoplasmic reticulum (SR) Ca(2+) leak is arrhythmogenic, it could represent a cellular basis for this paradox. METHODS/RESULTS: We evaluated the SR Ca(2+) leak with respect to sex differences in (i) afterload-induced cardiac hypertrophy (Hy) with preserved left ventricular (LV) function and (ii) end-stage HF. Cardiac function did not differ between sexes in both cardiac pathologies. Human cardiomyocytes isolated from female patients with Hy showed a significantly lower Ca(2+) spark frequency (CaSpF, confocal microscopy, Fluo3-AM) compared with men (P < 0.05). As Ca(2+) spark width and duration were similar in women and men, this difference in CaSpF did not yet translate into a significant difference of the calculated SR Ca(2+) leak between both sexes at this stage of disease (P = 0.14). Epifluorescence measurements (Fura2-AM) revealed comparable Ca(2+) cycling properties (diastolic Ca(2+) levels, amplitude of systolic Ca(2+) transients, SR Ca(2+) load) in patients of both sexes suffering from Hy. Additionally, the increased diastolic CaSpF in male patients with Hy did not yet translate into an elevated ratio of cells showing arrhythmic events (Ca(2+) waves, spontaneous Ca(2+) transients) (P = 0.77). In the transition to HF, both sexes showed an increase of the CaSpF (P < 0.05) and the sex dependence was even more pronounced. Female patients had a 69 ± 10% lower SR Ca(2+) leak (P < 0.05), which now even translated into a lower ratio of arrhythmic cells in female HF patients compared with men (P < 0.001). CONCLUSION: These data show that the SR Ca(2+) leak is lower in women than in men with comparable cardiac impairment. Since the SR Ca(2+) leak triggers delayed afterdepolarizations, our findings may explain why women are less prone to ventricular arrhythmias and confirm the rationale of therapeutic measures reducing the SR Ca(2+) leak.

Ca(2+) /calmodulin-dependent protein kinase II equally induces sarcoplasmic reticulum Ca(2+) leak in human ischaemic and dilated cardiomyopathy.

AIMS: The sarcoplasmic reticulum (SR) Ca(2+) leak is an important pathomechanism in heart failure (HF). It has been suggested that Ca(2+) /calmodulin-dependent protein kinase II (CaMKII) is only relevant for the induction of the SR Ca(2+) leak in non-ischaemic but not in ischaemic HF. Therefore, we investigated CaMKII and its targets as well as the functional effects of CaMKII inhibition in human ischaemic cardiomyopathy (ICM, n = 37) and dilated cardiomyopathy (DCM, n = 40). METHODS AND RESULTS: Western blots showed a significantly increased expression (by 54 ± 9%) and autophosphorylation at Thr286 (by 129 ± 29%, P < 0.05 each) of CaMKII in HF compared with healthy myocardium. However, no significant difference could be detected in ICM compared with DCM as to the expression and autophosphorylation of CaMKII nor the phosphorylation of the target sites ryanodine receptor 2 (RyR2)-S2809, RyR2-S2815, and phospholamban-Thr17. Isolated human cardiomyocytes (CMs) of patients with DCM and ICM showed a similar frequency of diastolic Ca(2+) sparks (confocal microscopy) as well as of major arrhythmic events (Ca(2+) waves, spontaneous Ca(2+) transients). Despite a slightly smaller size of Ca(2+) sparks in DCM (P < 0.01), the calculated SR Ca(2+) leak [Ca(2+) spark frequecy (CaSpF) × amplitude × width × duration] did not differ between CMs of ICM vs. DCM. Importantly, CaMKII inhibition by autocamide-2-related inhibitory peptide (AIP, 1 µmol/L) reduced the SR Ca(2+) leak by ∼80% in both aetiologies (P < 0.05 each) and effectively decreased the ratio of arrhythmic cells (P < 0.05). CONCLUSION: Functional and molecular measures of the SR Ca(2+) leak are comparable in human ICM and DCM. CaMKII is equally responsible for the induction of the 'RyR2 leakiness' in both pathologies. Thus, CaMKII inhibition as a therapeutic measure may not be restricted to patients suffering from DCM but rather may be beneficial for the majority of HF patients.