Transthoracic ultrasound localization microscopy of myocardial vasculature in patients.

Myocardial microvasculature and haemodynamics are indicative of potential microvascular diseases for patients with symptoms of coronary heart disease in the absence of obstructive coronary arteries. However, imaging microvascular structure and flow within the myocardium is challenging owing to the small size of the vessels and the constant movement of the patient's heart. Here we show the feasibility of transthoracic ultrasound localization microscopy for imaging myocardial microvasculature and haemodynamics in explanted pig hearts and in patients in vivo. Through a customized data-acquisition and processing pipeline with a cardiac phased-array probe, we leveraged motion correction and tracking to reconstruct the dynamics of microcirculation. For four patients, two of whom had impaired myocardial function, we obtained super-resolution images of myocardial vascular structure and flow using data acquired within a breath hold. Myocardial ultrasound localization microscopy may facilitate the understanding of myocardial microcirculation and the management of patients with cardiac microvascular diseases.

Ultrafast 3-D Transcutaneous Super Resolution Ultrasound Using Row-Column Array Specific Coherence-Based Beamforming and Rolling Acoustic Sub-aperture Processing: In Vitro, in Rabbit and in Human Study.

OBJECTIVE: This study aimed to realise 3-D super-resolution ultrasound imaging transcutaneously with a row-column array which has far fewer independent electronic channels and a wider field of view than typical fully addressed 2-D matrix arrays. The in vivo image quality of the row-column array is generally poor, particularly when imaging non-invasively. This study aimed to develop a suite of image formation and post-processing methods to improve image quality and demonstrate the feasibility of ultrasound localisation microscopy using a row-column array, transcutaneously on a rabbit model and in a human. METHODS: To achieve this, a processing pipeline was developed which included a new type of rolling window image reconstruction, which integrated a row-column array specific coherence-based beamforming technique with acoustic sub-aperture processing. This and other processing steps reduced the 'secondary' lobe artefacts, and noise and increased the effective frame rate, thereby enabling ultrasound localisation images to be produced. RESULTS: Using an in vitro cross tube, it was found that the procedure reduced the percentage of 'false' locations from ∼26% to ∼15% compared to orthogonal plane wave compounding. Additionally, it was found that the noise could be reduced by ∼7 dB and the effective frame rate was increased to over 4000 fps. In vivo, ultrasound localisation microscopy was used to produce images non-invasively of a rabbit kidney and a human thyroid. CONCLUSION: It has been demonstrated that the proposed methods using a row-column array can produce large field of view super-resolution microvascular images in vivo and in a human non-invasively.

The proarrhythmogenic role of autonomics and emerging neuromodulation approaches to prevent sudden death in cardiac ion channelopathies.

Ventricular arrhythmias in cardiac channelopathies are linked to autonomic triggers, which are sub-optimally targeted in current management strategies. Improved molecular understanding of cardiac channelopathies and cellular autonomic signalling could refine autonomic therapies to target the specific signalling pathways relevant to the specific aetiologies as well as the central nervous system centres involved in the cardiac autonomic regulation. This review summarizes key anatomical and physiological aspects of the cardiac autonomic nervous system and its impact on ventricular arrhythmias in primary inherited arrhythmia syndromes. Proarrhythmogenic autonomic effects and potential therapeutic targets in defined conditions including the Brugada syndrome, early repolarization syndrome, long QT syndrome, and catecholaminergic polymorphic ventricular tachycardia will be examined. Pharmacological and interventional neuromodulation options for these cardiac channelopathies are discussed. Promising new targets for cardiac neuromodulation include inhibitory and excitatory G-protein coupled receptors, neuropeptides, chemorepellents/attractants as well as the vagal and sympathetic nuclei in the central nervous system. Novel therapeutic strategies utilizing invasive and non-invasive deep brain/brain stem stimulation as well as the rapidly growing field of chemo-, opto-, or sonogenetics allowing cell-specific targeting to reduce ventricular arrhythmias are presented.

How to ablate the septo-pulmonary bundle: a case-based review of percutaneous ablation strategies to achieve roof line block.

Electrical conduction through cardiac muscle fibres separated from the main myocardial wall by layers of interposed adipose tissue are notoriously difficult to target by endocardial ablation alone. They are a recognised important cause for procedural failure due to the difficulties of delivering sufficient energy via the endocardial radiofrequency catheter to reach the outer epicardial layer without risking adverse events of the otherwise thin walled atria. Left atrial ablations for atrial fibrillation (AF) and tachycardia are commonly affected by the presence of several epicardial structures, with the septo-pulmonary bundle (SPB), Bachmann's bundle, and the ligament of Marshall all posing substantial challenges for endocardial procedures. Delivery of a transmural lesion set is essential for sustained pulmonary vein isolation and for conduction block across linear atrial lines which in turn has been described to translate into a reduced AF/atrial tachycardia recurrence rate. To overcome the limitations of endocardial-only approaches, surgical ablation techniques for epicardial or combined hybrid endo-epicardial ablations have been described to successfully target these connections. Yet, these techniques confer an increase in procedure complexity, duration, cost, and morbidity. Alternatively, coronary venous system ethanol ablation has been successfully employed by sub-selecting the vein of Marshall to facilitate mitral isthmus line block, although this approach is naturally limited to this area by the coronary venous anatomy. Increased awareness of the pathophysiological relevance of these epicardial structures and their intracardiac conduction patterns in the era of high-resolution 3D electro-anatomical mapping technology has allowed greater understanding of their contribution to the persistence of AF as well as failure to achieve transmural block by traditional ablation approaches. This might translate into novel catheter ablation strategies with procedural success rates comparable to surgical 'cut-and-sew' techniques. This review aims to give an overview of percutaneous catheter ablation strategies to target the SPB, an important cause of failed block across the roof line and isolation of the left atrial posterior wall and/or the pulmonary veins. Existing and investigational technologies will be discussed and an outlook of future approaches provided.

Current and novel percutaneous epicardial access techniques for electrophysiological interventions: A comparison of procedural success and safety.

Accessing the pericardial space safely and efficiently is an important skill for interventional cardiac electrophysiologist. With the increased recognition of the complexity of the 3-dimensional arrhythmogenic substrate due to advances in imaging and mapping technologies there has been an expansion of epicardial procedures in recent years. Equally, minimally invasive implantation of epicardial pacing, cardiac resynchronization, or defibrillation leads is expanding in specific patients where transvenous systems are contraindicated or their long term sequelae should be ideally avoided. Selective delivery of intrapericardial pharmacological antiarrhythmic therapy is yet another potential indication, albeit still investigational. The expanding indications for percutaneous epicardial procedures is contrasted by the still substantial risk and challenges associated with accessing the pericardial space. Myocardial perforation, coronary artery laceration, and damage to the surrounding organs are all recognized and feared complications. A number of innovative epicardial access techniques have been proposed to overcome the difficulties and risks of traditional dry subxiphoid punctures and may allow for more widespread use of epicardial access in the future. We review 10 different established and novel subxiphoidal epicardial access techniques describing procedural success rates, safety profile and overall experience. The technical aspects as well as access times and costs for extra equipment will be reviewed. Finally, an outlook of reported preclinical techniques awaiting in-human feasibility studies is provided.

Non-traditional implantable cardioverter-defibrillator configurations and insertion techniques: a review of contemporary options.

Implantable cardioverter-defibrillators (ICDs) have revolutionized the treatment of acquired or inherited cardiac diseases associated with a high risk of sudden cardiac death due to ventricular tachyarrhythmias. Contemporary ICD devices offer reliable arrhythmia detection and discrimination algorithms and deliver highly efficient tachytherapies. Percutaneously inserted transvenous defibrillator coils with pectoral generator placement are the first-line approach in the majority of adults due to their extensively documented clinical benefit and efficiency with comparably low periprocedural implantation risks as well as the option of providing pain-free tachycardia treatment via anti-tachycardia pacing (ATP), concomitant bradycardiaprotection, and incorporation in a cardiac resynchronization therapy if indicated. Yet, expanding ICD indications particularly among younger and more complex patient groups as well as the increasingly evident long-term consequences and complications associated with intravascular lead placements promoted the development of alternative ICD configurations. Most established in daily clinical practice is the subcutaneous ICD but other innovative extravascular approaches like epicardial, pericardial, extra-pleural, and most recently substernal defibrillator coil placements have been introduced as well to overcome shortcomings associated with traditional devices and allow for individualized treatment strategies tailored to the patients characteristics and needs. The review aims to provide practical solutions for common complications encountered with transvenous ICD systems including restricted venous access, high defibrillation/fibrillation thresholds (DFTs), and recurrent device infections. We summarize the contemporary options for non-traditional extravascular ICD configurations outlining indications, advantages, and disadvantages.

Ivabradine-sensitive incessant atrial tachycardia during pregnancy: a case report.

BACKGROUND: Automaticity is the dominant mechanism in maternal focal atrial tachycardia (FAT) during pregnancy and if incessant, can cause tachycardia-induced cardiomyopathy. Medication failure for FATs is common, however, for the subgroup due to increased automaticity ivabradine sensitivity has been described and may represent a valuable treatment option. Little data are available regarding the safety profile of ivabradine during pregnancy. CASE SUMMARY: We report the case of a 38-year-old woman with background of peripartum cardiomyopathy and incessant atrial tachycardia with deteriorating ventricular function during her second pregnancy unresponsive to betablockade and demonstrating the immediate successful rate-controlling effect of ivabradine. DISCUSSION: Early recognition of persistent maternal FAT is essential due to its frequent association with tachycardia-mediated cardiomyopathy. Our case report highlights the challenges of providing an equally safe and effective treatment of these notoriously difficult to treat arrhythmias during pregnancy. Ivabradine in combination with a betablocker can be effective for abnormal automaticity but its safety profile during pregnancy remains uncertain.

Review of the 2020 ESC Guidelines for the Diagnosis and Management of Atrial Fibrillation-What Has Changed and How Does This Affect Daily Practice.

The high prevalence of atrial fibrillation (AF) in the overall population and its association with substantial morbidity, increased mortality and health care cost has instigated significant basic and clinical research efforts over recent years. The publication of multiple new high-quality randomized multi-center trials in the area of AF management and the rapidly evolving technological progress in terms of diagnostic possibilities and catheter ablation in recent years demanded a revision of the previous ESC AF Guidelines from 2016. The 2020 guidelines provide up-to-date, evidence-based guidance for the management of AF. One of the most important innovations is the presentation of a new concept for structural characterization of AF (the "4S AF scheme") replacing the traditional classification based on its temporal pattern alone (paroxysmal-persistent-permanent). The 4S-AF-scheme highlights the importance of systematic assessment of stroke risk, severity of symptoms, total AF burden and underlying substrate as the foundation for effective and individualized AF treatment for each and every patient. Further novelties relate to the presentation of an easy and intuitive management pathway ("ABC pathway") and strengthening the recommendations for early rhythm control, in particular the role of first line catheter ablation in heart failure. Another core component of the guidelines is the focus on patient involvement to achieve optimal outcomes. Patient education, shared decision making and incorporation of patient values and patient reported outcome of treatment interventions as well as integrated care by a multidisciplinary team all have a central role in the proposed management pathway for AF.

Completely epicardial implantable cardioverter/defibrillator (ICD) and CRT-D systems: A case series and systematic literature review.

BACKGROUND: Epicardial ICD systems and CRT-Ds using high voltage coils represent an alternative to transvenous systems in patients without central venous access and prior device complications including infection. OBJECTIVE: We present a case series in the adult population of epicardial ICD/CRTD systems using high voltage epicardial coils. We summarize the existing data regarding techniques, efficacy, and safety. METHODS: A retrospective board approved medical record review was conducted for all patients undergoing epicardial ICD/CRTD placement at our institution between January 2010 and May 2020. The literature was reviewed for prior published trials, case reports, and case series of epicardial high voltage coil insertions. RESULTS: Eleven patients (six female, mean age 48 years) underwent epicardial ICD/CRTD implant including 5/11 completely epicardial CRTD systems. The procedure was performed via median sternotomy in eight patients, left anterior thoracotomy in two patients, and sub-xiphoid approach in one patient. After a mean follow up of 35 months, appropriate successful shocks were delivered in two (18%) patients and no patients received an inappropriate shock. Three of five (60%) patients had volumetric remodeling with CRT with significant improvement of LV EF. Device-related complications requiring a surgical/percutaneous revision or another DFT test occurred in six patients (54%). One patient died during follow up due to refractory heart failure. No cases of epicardial device infection, coronary artery compression, constrictive pericarditis, or erosion of defibrillator coils into intrathoracic organs were reported. No randomized studies comparing safety and efficacy of traditional transvenous or subcutaneous ICD systems and epicardial ICD systems using contemporary high voltage coils were found nor any studies directly comparing epicardial defibrillator patches versus epicardial coils. Thirteen case series and 24 single case reports published between 2004 and 2020 were identified describing in total a heterogenous group of 188 patients with ICD systems incorporating one or more epi- or pericardially positioned shock coils. CONCLUSION: The use of epicardial defibrillation coils for ICD/CRT-D is a feasible treatment option for patients with either failed or contraindicated transvenous ICD systems. Dedicated epicardial high voltage leads with integrated pace-sense electrodes and specialized delivery tools for minimal invasive implantations may improve longer term outcomes.

"Inside-Out" Central Venous Access approach with infraclavicular exit for right-sided CRT-D Implantation in bilateral brachiocephalic and superior vena cava occlusion.

The use of the "inside-out" approach with an infraclavicular exit site with a dedicated system in the presence of complex central venous occlusion is feasible and safe for the implantation of complex cardiac devices.

Differential effect of cardiac resynchronization therapy in patients with diabetes mellitus: a long-term retrospective cohort study.

AIMS: Cardiac resynchronization therapy (CRT) has become an important therapy in patients with heart failure with reduced left ventricular ejection fraction (LVEF). The effect of diabetes on long-term outcome in these patients is controversial. We assessed the effect of diabetes on long-term outcome in CRT patients and investigated the role of diabetes in ischaemic and non-ischaemic cardiomyopathy. METHODS AND RESULTS: All patients undergoing CRT implantation at our institution between November 2000 and January 2015 were enrolled. The study endpoints were (i) a composite of ventricular assist device (VAD) implantation, heart transplantation, or all-cause mortality; and (ii) reverse remodelling (improvement of LVEF ≥ 10% or reduction of left ventricular end-systolic volume ≥ 15%). Median follow-up of the 418 patients (age 64.6 ± 11.6 years, 22.5% female, 25.1% diabetes) was 4.8 years [inter-quartile range: 2.8;7.4]. Diabetic patients had an increased risk to reach the composite endpoint [adjusted hazard ratio (aHR) 1.48 [95% CI 1.12-2.16], P = 0.041]. Other factors associated with an increased risk to reach the composite endpoint were a lower body mass index or baseline LVEF (aHR 0.95 [0.91; 0.98] and 0.97 [0.95; 0.99], P < 0.01 each), and a higher New York Heart Association functional class or creatinine level (aHR 2.14 [1.38; 3.30] and 1.04 [1.01; 1.05], P < 0.05 each). Early response to CRT, defined as LVEF improvement ≥ 10%, was associated with a lower risk to reach the composite endpoint (aHR 0.60 [0.40; 0.89], P = 0.011). Reverse remodelling did not differ between diabetic and non-diabetic patients with respect to LVEF improvement ≥ 10% (aHR 0.60 [0.32; 1.14], P = 0.118). However, diabetes was associated with decreased reverse remodelling with respect to a reduction of left ventricular end-systolic volume ≥ 15% (aHR 0.45 [0.21; 0.97], P = 0.043). In patients with ischaemic cardiomyopathy, survival rates were not significantly different between diabetic and non-diabetic patients (HR 1.28 [0.83-1.97], P = 0.101), whereas in patients with non-ischaemic cardiomyopathy, diabetic patients had a higher risk of reaching the composite endpoint (HR 1.65 [1.06-2.58], P = 0.027). The latter effect was dependent on other risk factors (aHR 1.47 [0.83-2.61], P = 0.451). The risk of insulin-dependent patients was not significantly higher than in patients under oral antidiabetic drugs (HR 1.55 [95% CI 0.92-2.61], P = 0.102). CONCLUSIONS: Long-term follow-up revealed diabetes mellitus as independent risk factor for all-cause mortality, heart transplantation, or VAD in heart failure patients undergoing CRT. The detrimental effect of diabetes appeared to weigh heavier in patients with non-ischaemic compared with ischaemic cardiomyopathy.