Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology. Inflammatory ...cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis. At present, the reason why some patients recover without residual myocardial injury whereas others develop dilated cardiomyopathy is unclear. The relative roles of the pathogen, host genomics and environmental factors in disease progression and healing are still under discussion, including which viruses are active inducers and which are only bystanders. As a consequence, treatment strategies are not well established. In this Review, we summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with a special focus on virus-induced and virus-associated myocarditis. Furthermore, we identify knowledge gaps, appraise the available experimental models and propose future directions for the field. The current knowledge and open questions regarding the cardiovascular effects associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also discussed. This Review is the result of scientific cooperation of members of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society.
Introduction
Radiofrequency (RF) ablation is a commonly used tool in the invasive electrophysiology laboratory to treat a variety of rhythm disorders. Reliable creation of transmural ablation lesions ...is crucial for long‐term success. Lesion size index (LSI) is a multiparametric index that incorporates time, power, contact force (CF), and impedance data recorded during RF ablation in a weighted formula and has been shown to predict the extent of myocardial tissue lesions. Whether the force stability of contact influences lesion size in LSI‐guided ablations is unknown.
Objectives
The aim of this study was to analyze the influence of the force stability of contact on lesion size during LSI‐guided ablations in an ex‐vivo model.
Methods and Results
A total of 267 RF lesions (n = 6 hearts) were created on porcine myocardial slabs by using an open‐tip irrigated ablation catheter with the following settings: 35 W with either intermittent (varied between 0 and up to 20 g), variable (10 to 20 g), or constant tissue contact (15 g) in a perpendicular or parallel fashion (applied manually) up to a target LSI of either 5 or 6. Subsequently, lesion width and depth were determined. Lesion width was mainly influenced by catheter tip orientation and LSI, whereas lesion depth was mainly influenced by LSI alone. The force stability of catheter contact had no relevant impact on lesion width or depth.
Conclusion
The force stability of catheter contact has only little effect on lesion depth or width in LSI‐guided catheter ablation while the catheter orientation primarily affects lesion width.
Induced pluripotent stem (iPS) cells generated from accessible adult cells of patients with genetic diseases open unprecedented opportunities for exploring the pathophysiology of human diseases in ...vitro. Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) is an inherited cardiac disorder that is caused by mutations in the cardiac ryanodine receptor type 2 gene (RYR2) and is characterized by stress-induced ventricular arrhythmia that can lead to sudden cardiac death in young individuals. The aim of this study was to generate iPS cells from a patient with CPVT1 and determine whether iPS cell-derived cardiomyocytes carrying patient specific RYR2 mutation recapitulate the disease phenotype in vitro.
iPS cells were derived from dermal fibroblasts of healthy donors and a patient with CPVT1 carrying the novel heterozygous autosomal dominant mutation p.F2483I in the RYR2. Functional properties of iPS cell derived-cardiomyocytes were analyzed by using whole-cell current and voltage clamp and calcium imaging techniques.
Patch-clamp recordings revealed arrhythmias and delayed afterdepolarizations (DADs) after catecholaminergic stimulation of CPVT1-iPS cell-derived cardiomyocytes. Calcium imaging studies showed that, compared to healthy cardiomyocytes, CPVT1-cardiomyocytes exhibit higher amplitudes and longer durations of spontaneous Ca(2+) release events at basal state. In addition, in CPVT1-cardiomyocytes the Ca(2+)-induced Ca(2+)-release events continued after repolarization and were abolished by increasing the cytosolic cAMP levels with forskolin.
This study demonstrates the suitability of iPS cells in modeling RYR2-related cardiac disorders in vitro and opens new opportunities for investigating the disease mechanism in vitro, developing new drugs, predicting their toxicity, and optimizing current treatment strategies.
Atrial and ventricular arrhythmias significantly contribute to morbidity and mortality of patients with cardiac disease. Ablation of these arrhythmias has shown to improve clinical outcomes, yet ...targeted ablation strategies rely on proper mapping capabilities. In the present study, we compare different modes of high-resolution mapping in clinically relevant arrhythmias using HD grid.
Using the Advisor™ HD Grid Mapping Catheter in either the standard, the wave (bipolar along spline and bipolar orthogonal) or the wave diagonal setting, low-voltage areas were determined. Low-voltage was defined as local electrograms with an amplitude <0.5 mV (bipolar; atria/ventricle) or <4 mV (unipolar; ventricle). Ultra high-density mapping in 47 patients with ventricular tachycardia, ventricular premature beats, atrial fibrillation and atrial tachycardia provided reliable information for the understanding of the arrhythmia mechanism resulting in safe ablation procedures. Regions of low voltage were significantly decreased by 14 ± 2% and 31 ± 3% with wave and wave diagonal settings as compared to standard settings, respectively.
Substrate mapping and risk stratification relies on proper low voltage discrimination. Even though the Advisor™ HD Grid Mapping Catheter was safely used in all cases, the extent of low voltage areas was mapping-mode dependent.
Implantable loop recorders (ILR) are a valuable tool for the investigation of unexplainedsyncopal episodes. The aim of this retrospective single center study was to identify predictive factors for ...pacemaker implantation in patients with unexplained syncope who underwent ILR insertion.
One hundred six patients were retrospectively analyzed (mean age 59.1 years; 47.2% male) with unexplained syncope and negative conventional testing who underwent ILR implantation. The pri- mary study endpoint was detection of symptomatic or asymptomatic bradycardia requiring pacemaker implantation.
The average follow-up period after ILR implantation was 20 ± 15 months. Pacemaker im- plantation according to current guidelines was necessary in 22 (20.8%) patients, mean duration until index bradycardia was 81 ± 88 (2-350) days. Ten (45.5%) patients received a pacemaker due to sinus arrest, 7 (31.8%) patients due to third-degree atrioventricular block, 2 (9.1%) patients due to second- degree atrioventricular block and 1 (4.5%) patient due to atrial fibrillation with a slow ventricular rate. Three factors remained significant in multivariate analysis: obesity, which defined by a body mass index above 30 kg/m2 (OR: 7.39, p = 0.014), a right bundle branch block (OR: 9.40, p = 0.023) and chronic renal failure as defined by a glomerular filtration rate of less than 60 mL/min (OR: 6.42, p = 0.035).
Bradycardia is a frequent finding in patients undergoing ILR implantation due to un- explained syncope. Obesity, right bundle branch block and chronic renal failure are independent clinical predictors of pacemaker implantation.
We report a 55‐year‐old male patient with lone paroxysmal atrial fibrillation who underwent routine transesophageal echocardiography (TOE) at our institution. In a mid‐esophageal 125° three‐chamber ...angulation, a distinct thinning of the left atrial (LA) wall was observed, forming a 7 × 4 mm canal with only a small membrane separating the LA from the pericardial space. Cardiac magnetic resonance imaging diagnosed a small LA diverticulum. To the best of our knowledge, this is the first manuscript describing detection of a small LA diverticulum via TOE.
Background
Catheter ablation of atrial fibrillation has been associated with left‐sided phrenic nerve palsy. Knowledge of the individual left phrenic nerve course therefore is essential to prevent ...nerve injury. The aim of this study was to test the feasibility of an intraprocedural pace mapping and reconstruction of the left phrenic nerve course and to characterize which anatomical areas are affected.
Methods
In patients undergoing left atrial catheter ablation, a three‐dimensional map of the left atrial anatomical structures was created. The left‐sided phrenic nerve course was determined by high‐output pace mapping and reconstructed in the map.
Results
In this study, 40 patients with atrial fibrillation or atrial tachycardias were included. Left phrenic nerve capture was observed in 23 (57.5%) patients. Phrenic nerve was captured in 22 (55%) patients inside the left atrial appendage, in 22 (55%) in distal parts, in 21 (53%) in medial parts, and in two (5%) in ostial parts of the appendage. In three (7.5%) patients, capture was found in the distal coronary sinus and in one (2.5%) patient in the left atrium near the left atrial appendage ostium. Ablation target was changed due to direct spatial relationship to the phrenic nerve in three (7.5%) patients. No phrenic nerve palsy was observed.
Conclusions
Left‐sided phrenic nerve capture was found inside and around the left atrial appendage in the majority of patients and additionally in the distal coronary sinus. Phrenic nerve mapping and reconstruction can easily be performed and should be considered prior catheter ablations in potential affected areas.
Abstract Background We evaluated the prognostic value of mid-regional proadrenomedullin (MR-proADM) in atrial fibrillation (AF) patients undergoing radiofrequency ablation. Methods Plasma ...concentrations of MR-proADM were measured at baseline and after 12 months in 87 AF patients in whom radiofrequency ablation was performed. The association between MR-proADM and AF recurrence was tested by univariable and multivariable Cox models. Results In all 87 patients radiofrequency ablation was successfully performed. Of the total population 54% had paroxysmal AF. The mean left ventricular ejection fraction was 54% (minimum 25%). After 12 months of follow-up, 71% of the patients were free of AF recurrence. At baseline, mean MR-proADM in the total population was 0.72 nmol/l ± 0.22. Patients with AF recurrence had significantly higher baseline MR-proADM (0.89 nmol/l ± 0.29) as compared with patients without AF recurrence (0.65 nmol/l ± 0.14; p < 0.001). After 12 months, mean MR-proADM plasma concentration remained higher in patients with AF recurrence (0.81 nmol/l ± 0.22 as compared with patients free of AF 0.54 nmol/l ± 0.20; p < 0.001). Receiver operating characteristic (ROC) curve analysis for MR-proADM yields a specificity of 98% and a sensitivity of 64% with an optimal cut-off value of 0.82 nmol/l to predict recurrence of AF after catheter ablation. In the logistic regression analysis only MR-proADM remained independently predictive for AF recurrence. Conclusion This is the first study revealing the association between MR-proADM elevation before ablation and poor outcomes after ablation of AF. Larger studies are needed to validate these results.
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