A real-world experience of subcutaneous and transvenous implantable cardiac defibrillators-comparison with the PRAETORIAN study.

Background: PRAETORIAN is the first randomized controlled trial that demonstrated the noninferiority of subcutaneous ICD (S-ICD) in comparison with transvenous ICD (TV-ICD). We retrospectively reviewed electronic records of patients with ICD implanted over the past 6 years, with the primary objective to compare our real-world single tertiary center experience with the randomized data from the PRAETORIAN study. Methods: Seventy S-ICD patients were compared with 197 TV-ICD patients, from July 2014 to June 2020 retrospectively, over a median period of 1304 days (296-2451 days). Primary composite endpoints included inappropriate shocks and device-related malfunctions. Results: Patients with S-ICD implantation were younger than those who received TV-ICD (mean, 49.7 years vs 63.9 years, p < .001). About 31.4% of S-ICDs were implanted for secondary prevention, and 58.6% of S-ICD patients had ischemic cardiomyopathy (ICM) with a median left ventricular ejection fraction of 32.5% (range: 10-67%). S-ICDs and TV-ICD had statistically similar inappropriate shocks (4.3% vs 4.6%, p = .78), device-related complications (11.4% vs 9.1%, p = .93), and the overall primary endpoints (15.7% vs 13.7%, p = .68). The findings remained the same even after age and gender adjustments and time-dependent analysis. Conclusion: Although single-center experience with a small number of S-ICD patients, results of the PRAETORIAN study has been replicated in our real-world experience of S-ICD and TV-ICD implantations across diverse etiologies, indications, and age groups confirming the comparable performance of S-ICD and TV-ICD when implanted in selected patients.

Impact of a high-density grid catheter on long-term outcomes for structural heart disease ventricular tachycardia ablation.

BACKGROUND: Substrate mapping has highlighted the importance of targeting diastolic conduction channels and late potentials during ventricular tachycardia (VT) ablation. State-of-the-art multipolar mapping catheters have enhanced mapping capabilities. The purpose of this study was to investigate whether long-term outcomes were improved with the use of a HD Grid mapping catheter combining complementary mapping strategies in patients with structural heart disease VT. METHODS: Consecutive patients underwent VT ablation assigned to either HD Grid, Pentaray, Duodeca, or point-by-point (PbyP) RF mapping catheters. Clinical endpoints included recurrent anti-tachycardia pacing (ATP), appropriate shock, asymptomatic non-sustained VT, or all-cause death. RESULTS: Seventy-three procedures were performed (33 HD Grid, 22 Pentaray, 12 Duodeca, and 6 PbyP) with no significant difference in baseline characteristics. Substrate mapping was performed in 97% of cases. Activation maps were generated in 82% of HD Grid cases (Pentaray 64%; Duodeca 92%; PbyP 33% (p = 0.025)) with similar trends in entrainment and pace mapping. Elimination of all VTs occurred in 79% of HD Grid cases (Pentaray 55%; Duodeca 83%; PbyP 33% (p = 0.04)). With a mean follow-up of 372 ± 234 days, freedom from recurrent ATP and shock was 97% and 100% respectively in the HD Grid group (Pentaray 64%, 82%; Duodeca 58%, 83%; PbyP 33%, 33% (log rank p = 0.0042, p = 0.0002)). CONCLUSIONS: This study highlights a step-wise improvement in survival free from ICD therapies as the density of mapping capability increases. By using a high-density mapping catheter and combining complementary mapping strategies in a strict procedural workflow, long-term clinical outcomes are improved.

Prospective cardiovascular magnetic resonance imaging in adults with Alström syndrome: silent progression of diffuse interstitial fibrosis.

BACKGROUND: Alström syndrome (ALMS) is a rare ciliopathy characterised by early onset insulin resistance, obesity, and dyslipidaemia and is a model for diseases that have huge social, health and economic impact. Cardiomyopathy develops in the majority, with high rates of morbidity and mortality, the definitive features of which are coarse replacement fibrosis and diffuse myocardial fibrosis (DIF). The pathogenesis of heart failure is thought to involve fibroblast accumulation and expansion of the extracellular matrix with excess protein deposition, leading to distorted organ architecture and impaired contractile function. Consecutive adults with genetically proven ALMS attending the National Centre for Rare Disease in Birmingham, England were studied. All patients underwent serial CMR, echocardiography and venous blood sampling, with computed tomography coronary angiography (CTCA) performed to assess severity of CAD. The aims of this study were: 1) to evaluate changes over time in DIF by cardiovascular magnetic resonance tissue characterization in ALMS; 2) to examine whether changes in DIF are associated with alteration in systolic or diastolic function; and 3) to evaluate the frequency and severity of coronary artery disease as a confounder for progression of ischaemic versus non-ischaemic fibrosis. RESULTS: In total, 30/32 adults (63% male; 67% White British) participated. The median age at first scan was 21.3 years (interquartile range: 19.0-32.6) and participants were followed for a maximum of 67 months. Only 4 patients had significant coronary artery stenosis on post-mortem, invasive coronary angiography or CTCA. Mid short axis myocardial T1 times, myocardial extracellular volume, and left ventricular mass increased significantly over time, by an average of 21.8 ms (95% CI 17.4-26.1; p < 0.001), 1.1 percentage points (0.6-1.6, p < 0.001), and 2.8 g/m2 (1.9-3.7; p < 0.001) per year, respectively. These changes were not associated with significant deterioration in myocardial structure or function. CONCLUSIONS: This is the first comprehensive prospective study demonstrating progression of DIF in ALMS over time, although no structural or functional consequences were noted within a median three and a half years' follow up. Further study is warranted to define whether DIF is a by-stander or the driver to impaired contractile function, heart failure and death.

Enhanced ventricular tachycardia substrate resolution with a novel omnipolar high-density mapping catheter: the omnimapping study.

BACKGROUND: Defining diastolic slow-conduction channels within the borderzone (BZ) of scar-dependent re-entrant ventricular tachycardia (VT) is key for effective mapping and ablation strategies. Understanding wavefront propagation is driving advances in high-density (HD) mapping. The newly developed Advisor™ HD Grid Mapping Catheter (HD GRID) has equidistant spacing of 16, 1 mm electrodes in a 4 × 4 3 mm interspaced arrangement allowing bipolar recordings along and uniquely across the splines (orthogonal vector) to facilitate substrate mapping in a WAVE configuration (WAVE). The purpose of this study was to determine the relative importance of the WAVE configuration compared to the STANDARD linear-only bipolar configuration (STANDARD) in defining VT substrate. METHODS: Thirteen patients underwent VT ablation at our institution. In all cases, a substrate map was constructed with the HD GRID in the WAVE configuration (conWAVE) to guide ablation strategy. At the end of the procedure, the voltage map was remapped in the STANDARD configuration (conSTANDARD) using the turbo-map function. Detailed post-hoc analysis of the WAVE and STANDARD maps was performed blinded to the configuration. Quantification of total scar area, BZ and dense scar area with assessment of conduction channels (CC) was performed. RESULTS: The substrate maps conSTANDARD vs conWAVE showed statistically significant differences in the total scar area (56 ± 32 cm2 vs 51 ± 30 cm2; p = 0.035), dense scar area (36 ± 25 cm2 vs 29 ± 22 cm2; p = 0.002) and number of CC (3.3 ± 1.6 vs 4.8 ± 2.5; p = 0.026). conWAVE collected more points than the conSTANDARD settings (p = 0.001); however, it used fewer points in map construction (p = 0.023). CONCLUSIONS: The multipolar Advisor™ HD Grid Mapping Catheter in conWAVE provides more efficient point acquisition and greater VT substrate definition of the borderzone particularly at the low-voltage range compared to conSTANDARD. This greater resolution within the low-voltage range facilitated CC definition and quantification within the scar, which is essential in guiding the ablation strategy.

Long-term follow-up of normal and structural heart ventricular tachycardia catheter ablation: real-world experience from a UK tertiary centre.

Background: Ventricular tachycardia (VT) is associated with increased morbidity and mortality. There is growing evidence for the effectiveness of catheter ablation in improving outcomes in patients with recurrent VT. Consequently the threshold for referral for VT ablation has fallen over recent years, resulting in increased number of procedures. Objective: To evaluate the effectiveness and safety of VT ablation in a real-world tertiary centre setting. Methods: This is a prospective analysis of all VT ablation cases performed at University Hospital Coventry. Follow-up data were obtained from review of electronic medical records and patient interview. The primary endpoint for normal heart VT was death, cardiovascular hospitalisation and VT recurrence, and for structural heart VT was arrhythmic death, VT storm (>3 episodes within 24 hours) or appropriate shock. Results: Forty-seven patients underwent 53 procedures from January 2012 to January 2018. The mean age ±SD was 57±15 years, 68% were male, 81% were Caucasian and 66% were elective cases. The aetiology of VT included normal heart (49%), ischaemic cardiomyopathy (ICM, 36%), dilated cardiomyopathy (9%), hypertrophic cardiomyopathy (4%) and valvular heart disease (2%). Procedural success occurred in 83%, with six major complications. After a median follow-up of 231 days (lower quartile 133, upper quartile 631), the primary outcome occurred in 28% of patients. There were two non-arrhythmic deaths (4%). At a median follow-up of 193 days (129-468), the primary outcome occurred in 19% of patients with ICM, while VT storm/appropriate shocks occurred in three patients (17%). Conclusions: Our real-world registry confirms that VT ablation is safe, and is associated with high acute procedural success and long-term outcomes comparable with randomised controlled studies.

Superparamagnetic iron oxide nanoparticles function as a long-term, multi-modal imaging label for non-invasive tracking of implanted progenitor cells.

The purpose of this study was to determine the ability of superparamagnetic iron oxide (SPIO) nanoparticles to function as a long-term tracking label for multi-modal imaging of implanted engineered tissues containing muscle-derived progenitor cells using magnetic resonance imaging (MRI) and X-ray micro-computed tomography (µCT). SPIO-labeled primary myoblasts were embedded in fibrin sealant and imaged to obtain intensity data by MRI or radio-opacity information by µCT. Each imaging modality displayed a detection gradient that matched increasing SPIO concentrations. Labeled cells were then incorporated in fibrin sealant, injected into the atrioventricular groove of rat hearts, and imaged in vivo and ex vivo for up to 1 year. Transplanted cells were identified in intact animals and isolated hearts using both imaging modalities. MRI was better able to detect minuscule amounts of SPIO nanoparticles, while µCT more precisely identified the location of heavily-labeled cells. Histological analyses confirmed that iron oxide particles were confined to viable, skeletal muscle-derived cells in the implant at the expected location based on MRI and µCT. These analyses showed no evidence of phagocytosis of labeled cells by macrophages or release of nanoparticles from transplanted cells. In conclusion, we established that SPIO nanoparticles function as a sensitive and specific long-term label for MRI and µCT, respectively. Our findings will enable investigators interested in regenerative therapies to non-invasively and serially acquire complementary, high-resolution images of transplanted cells for one year using a single label.

Microcarrier-based expansion of adult murine side population stem cells.

The lack of reliable methods to efficiently isolate and propagate stem cell populations is a significant obstacle to the advancement of cell-based therapies for human diseases. One isolation technique is based on efflux of the fluorophore Hoechst 33342. Using fluorescence-activated cell sorting (FACS), a sub-population containing adult stem cells has been identified in a multitude of tissues in every mammalian species examined. These rare cells are referred to as the 'side population' or SP due to a distinctive FACS profile that results from weak staining by Hoechst dye. Although the SP contains multi-potent cells capable of differentiating toward hematopoietic and mesenchymal lineages; there is currently no method to efficiently expand them. Here, we describe a spinner-flask culture system containing C2C12 myoblasts attached to spherical microcarriers that act to support the growth of non-adherent, post-natal murine skeletal muscle and bone marrow SP cells. Using FACS and hemocytometry, we show expansion of unfractionated EGFP⁺ SP cells over 6 wks. A significant number of these cells retain characteristics of freshly-isolated, unfractionated SP cells with respect to protein expression and dye efflux capacity. Expansion of the SP will permit further study of these heterogeneous cells and determine their therapeutic potential for regenerative and reparative therapies.