Endomysial fibrosis, rather than overall connective tissue content, is the main determinant of conduction disturbances in human atrial fibrillation.

AIMS: Although in persistent atrial fibrillation (AF) a complex AF substrate characterized by a high incidence of conduction block has been reported, relatively little is known about AF complexity in paroxysmal AF (pAF). Also, the relative contribution of various aspects of structural alterations to conduction disturbances is not clear. In particular, the contribution of endomysial fibrosis to conduction disturbances during progression of AF has not been studied yet. METHODS AND RESULTS: During cardiac surgery, epicardial high-density mapping was performed in patients with acutely induced (aAF, n = 11), pAF (n = 12), and longstanding persistent AF (persAF, n = 9) on the right atrial (RA) wall, the posterior left atrial wall (pLA) and the LA appendage (LAA). In RA appendages, overall and endomysial (myocyte-to-myocyte distances) fibrosis and connexin 43 (Cx43) distribution were quantified. Unipolar AF electrogram analysis showed a more complex pattern with a larger number of narrower waves, more breakthroughs and a higher fractionation index (FI) in persAF compared with aAF and pAF, with no differences between aAF and pAF. The FI was consistently higher at the pLA compared with the RA. Structurally, Cx43 lateralization increased with AF progression (aAF = 7.5 ± 8.9%, pAF = 24.7 ± 11.1%, persAF = 35.1 ± 11.4%, P < 0.001). Endomysial but not overall fibrosis correlated with AF complexity (r = 0.57, P = 0.001; r = 0.23, P = 0.20; respectively). CONCLUSIONS: Atrial fibrillation complexity is highly variable in patients with pAF, but not significantly higher than in patients with acutely induced AF, while in patients with persistent AF complexity is higher. Among the structural alterations studied, endomysial fibrosis, but not overall fibrosis, is the strongest determinant of AF complexity.

The TRPM4 channel is functionally important for the beneficial cardiac remodeling induced by endurance training.

Cardiac hypertrophy (CH) is an adaptive process that exists in two distinct forms and allows the heart to adequately respond to an organism's needs. The first form of CH is physiological, adaptive and reversible. The second is pathological, irreversible and associated with fibrosis and cardiomyocyte death. CH involves multiple molecular mechanisms that are still not completely defined but it is now accepted that physiological CH is associated more with the PI3-K/Akt pathway while the main signaling cascade activated in pathological CH involves the Calcineurin-NFAT pathway. It was recently demonstrated that the TRPM4 channel may act as a negative regulator of pathological CH by regulating calcium entry and thus the Cn-NFAT pathway. In this study, we examined if the TRPM4 channel is involved in the physiological CH process. We evaluated the effects of 4 weeks endurance training on the hearts of Trpm4 +/+ and Trpm4 -/- mice. We identified an elevated functional expression of the TRPM4 channel in cardiomyocytes after endurance training suggesting a potential role for the channel in physiological CH. We then observed that Trpm4 +/+ mice displayed left ventricular hypertrophy after endurance training associated with enhanced cardiac function. By contrast, Trpm4 -/- mice did not develop these adaptions. While Trpm4 -/- mice did not develop gross cardiac hypertrophy, the cardiomyocyte surface area was larger and associated with an increase of Tunel positive cells. Endurance training in Trpm4 +/+ mice did not increase DNA fragmentation in the heart. Endurance training in Trpm4 +/+ mice was associated with activation of the classical physiological CH Akt pathway while Trpm4 -/- favored the Calcineurin pathway. Calcium studies demonstrated that TRPM4 channel negatively regulates calcium entry providing support for activation of the Cn-NFAT pathway in Trpm4 -/- mice. In conclusion, we provide evidence for the functional expression of TRPM4 channel in response to endurance training. This expression may help to maintain the balance between physiological and pathological hypertrophy.

Wearable Cardioverter Defibrillator Shortens the Lengths of Stay in Patients with Left Ventricular Dysfunction after Myocardial Infarction: A Single-Centre Real-World Experience.

The wearable cardioverter defibrillator (WCD) has been proven to be effective in preventing sudden cardiac death (SCD) in patients soon after acute myocardial infarction (AMI) and left ventricular ejection fraction (LVEF) ≤35%. The aim of this study was to assess whether a WCD may shorten the length of an initial hospital stay (total length, days in the intensive care unit (ICU) and in the acute cardiac care unit (ACCU)) among these patients. This was a single-centre, retrospective observational study of patients referred for the management of SCD risk post-AMI and LVEF ≤35%, in a tertiary care hospital. The clinical characteristics and length of index hospitalization of the group of patients discharged, with or without WCD, were compared. A propensity score analysis was performed, then weighted regression models were conducted. A total of 101 patients in the WCD group and 29 in the control group were enrolled in the analysis. In the weighted regression models, WCD significantly reduced the days spent in ACCU (p < 0.001). WCD patients had significantly fewer days spent in ACCU (5.5 ± 2.6 vs. 8.4 ± 12.8 days, p < 0.001) and shorter hospitalizations (10.2 ± 5.7 vs. 13.4 ± 17.6 days, p = 0.005), compared with the control group. It was concluded that the WCD appears to reduce the total length of hospitalization and lengths of stay in ACCU for patients post-AMI and with left ventricular dysfunction.

Virtual Reality Hypnosis in the Electrophysiology Lab: When Human Treatments Are Better than Virtual Ones.

Aims: Virtual reality hypnosis (VRH) has been used successfully in various clinical settings to decrease anxiety and the sensation of pain. We aimed to investigate the feasibility and safety of VRH in patients undergoing electrophysiology and pacing procedures under conscious sedation. Methods: During a two-month period, VRH support was proposed and accepted by 25 patients undergoing electrophysiological procedures. Data were compared with a control group (n = 61) enrolled during the following three-month period. Both groups underwent the measurement of the duration of intervention, the consumption of analgesics and hypnotics, and their pain and comfort using a validated visual analogue scale (VAS 0−10). Results: The baseline characteristics were comparable in both groups, including age. There were no differences in procedure duration (46 (±29) vs. 56 (±32) min, p = 0.18) or in hypnotic/antalgic consumption (midazolam 1.95 (±1.44) vs. 2.00 (±1.22) mg, p = 0.83; sufentanyl 3.78 (±2.87) vs. 3.58 (±2.48) µg, p = 0.9) between the control and VRH groups. In a multivariate analysis, the use of VRH was independently associated with lower comfort during the procedure assessed by postoperative visual analogue scale (OR 15.00 [95% CI 4.77−47.16], p < 0.01). There was no influence of VRH use on pain or drug consumption. Conclusions: In our experience, compared with VRH, human care is preferable during procedures in electrophysiology lab to improve the comfort of the patient. VRH has no influence on pain or drug consumption.

Intracardiac thrombus: a good indication of ultrasound image integration system (Cartosound) for radiofrequency ablation.

We describe the case of a young man suffering from incessant ventricular tachycardia and a chronic apical left ventricular thrombus. We performed radiofrequency ablation of this tachycardia emerging from the border zone of the septoapical anevrism, near the apical thrombus. We used Cartosound system to avoid manipulation of catheter in the thrombus. We demonstrate, in this case, that the technique is feasible and safe.

Occurrence of Incomplete Endothelialization Causing Residual Permeability After Left Atrial Appendage Closure.

AIMS: Percutaneous left atrial appendage (LAA) occlusion is occasionally incomplete, with residual permeability of the LAA on cardiac computed tomography. The cause for this is unclear. Our objective was to determine if residual permeability was related to incomplete endothelialization. METHODS: A total of 35 consecutive patients contraindicated for anticoagulant therapy admitted for LAA occlusion were included; 12 patients received a Watchman device (Boston Scientific) and 23 patients received an Amplatzer Cardiac Plug (St. Jude Medical). Incomplete endothelialization was defined as residual permeability on cardiac computed tomography without peridevice leak on transesophageal echocardiography at follow-up. RESULTS: Five patients did not receive cardiac computed tomography. After 10 ± 6 months of follow-up, residual permeability of the LAA (at least partial) was recorded on cardiac computed tomography in 21 of 30 patients (70%). Seven of 30 patients presented with a peridevice leak on transesophageal echocardiography. Among the remaining 23 patients, 14 (61%) presented with incomplete endothelialization and 9 (39%) presented with complete endothelialization. There was no statistical difference between the patients presenting with complete vs incomplete endothelialization. CONCLUSION: We found that incomplete endothelialization, defined as residual permeability on cardiac computed tomography without peridevice leak on transesophageal echocardiography, occurred in 61% of the patients after 10 ± 6 months of percutaneous LAA closure. Predisposing factors and appropriate monitoring of LAA patients remain to be determined in larger cohorts.

Real-time atrial wall imaging during radiofrequency ablation in a porcine model.

BACKGROUND: Real-time monitoring of radiofrequency (RF) ablation remains challenging. OBJECTIVE: We used intravascular ultrasound (IVUS) to describe atrial wall changes during RF ablation and to assess the extent of RF-induced lesions. METHODS: In 9 piglets, RF and IVUS catheters were coupled and introduced into the right atrium. RF applications were performed along the intercaval line. Corresponding IVUS images were analyzed. Wall thickness was correlated with electrogram (EGM) changes (n = 9) and histology (n = 5). RESULTS: There were 66 RF applications performed in 57 sites. IVUS provided real-time imaging of the atrial wall during RF application in all but 2 sites. IVUS demonstrated significant (>20%) and immediate increase in atrial wall thickness in 71.4% of RF applications. It showed epicardial or intramyocardial effusion in 30% of cases, 2 steam pops, 1 intramural hematoma, and 1 thrombus. EGM amplitude decreased and thickness increased after RF application than at baseline (2.20 ± 1.11 to 0.99 ± 0.62 mV and 1.34 ± 0.53 to 1.93 ± 0.80 mm, respectively; P < .001 for each). However, EGM and thickness changes were poorly correlated (r = 0.43; P < .05). Histologically and echographically measured thicknesses were correlated (r = 0.71; P = .004), but echographic thickness change was not related to histological lesion transmurality. CONCLUSION: An IVUS probe coupled to an RF catheter can provide relevant real-time imaging of the atrial wall during ablation. Although thickness change does not appear as a good predictor of the transmural extent, direct visualization and monitoring of RF application may provide new information to guide and secure RF ablation.

Trpm4 gene invalidation leads to cardiac hypertrophy and electrophysiological alterations.

RATIONALE: TRPM4 is a non-selective Ca2+-activated cation channel expressed in the heart, particularly in the atria or conduction tissue. Mutations in the Trpm4 gene were recently associated with several human conduction disorders such as Brugada syndrome. TRPM4 channel has also been implicated at the ventricular level, in inotropism or in arrhythmia genesis due to stresses such as ß-adrenergic stimulation, ischemia-reperfusion, and hypoxia re-oxygenation. However, the physiological role of the TRPM4 channel in the healthy heart remains unclear. OBJECTIVES: We aimed to investigate the role of the TRPM4 channel on whole cardiac function with a Trpm4 gene knock-out mouse (Trpm4-/-) model. METHODS AND RESULTS: Morpho-functional analysis revealed left ventricular (LV) eccentric hypertrophy in Trpm4-/- mice, with an increase in both wall thickness and chamber size in the adult mouse (aged 32 weeks) when compared to Trpm4+/+ littermate controls. Immunofluorescence on frozen heart cryosections and qPCR analysis showed no fibrosis or cellular hypertrophy. Instead, cardiomyocytes in Trpm4-/- mice were smaller than Trpm4+/+with a higher density. Immunofluorescent labeling for phospho-histone H3, a mitosis marker, showed that the number of mitotic myocytes was increased 3-fold in the Trpm4-/-neonatal stage, suggesting hyperplasia. Adult Trpm4-/- mice presented multilevel conduction blocks, as attested by PR and QRS lengthening in surface ECGs and confirmed by intracardiac exploration. Trpm4-/-mice also exhibited Luciani-Wenckebach atrioventricular blocks, which were reduced following atropine infusion, suggesting paroxysmal parasympathetic overdrive. In addition, Trpm4-/- mice exhibited shorter action potentials in atrial cells. This shortening was unrelated to modifications of the voltage-gated Ca2+ or K+ currents involved in the repolarizing phase. CONCLUSIONS: TRPM4 has pleiotropic roles in the heart, including the regulation of conduction and cellular electrical activity which impact heart development.

Pro- and anti-arrhythmic effects of anti-inflammatory drugs.

Inflammatory process is strongly associated with cardiac arrhythmia, either as a cause or a consequence. Antiinflammatory drugs are widely prescribed, and some of them have been associated with an increased cardiovascular risk. Then, the eventual pro- or anti-arrhythmic effect of these drugs is of high interest for clinical practice. This review summarizes pro- and anti-arrhythmic effects of anti-inflammatory drugs, based on the analysis of published clinical trials. Cardiac arrhythmias are divided into atrial fibrillation (AF) and ventricular arrhythmias. Based on the literature and on pathophysiology, post-operative AF and post-ablative AF are analyzed separately. After a brief overview of fundamental mechanisms of arrhythmia and their relationship to inflammation, we thought to examine corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), and colchicine effects on cardiac arrhythmias. All anti-inflammatory drugs have demonstrated anti-arrhythmic properties in post operative AF. Apart from this specific condition, NSAIDs and corticosteroids increase the risk of AF. Regarding ventricular arrhythmias the effects of these drugs are not well established and would require further investigations.

Epstein Barr virus (EBV) and acute myopericarditis in an immunocompetent patient: first demonstrated case and discussion.

Acute viral infections can lead to heart inflammation, including acute myocarditis. We report the first case of myopericarditis in a young immunocompetent adult, in the context of recent Epstein-Barr virus infection. Clinical presentation was common acute pericarditis, but with risk biomarkers: high troponin I levels and multiple inflammation-compatible images on MRI. Diagnosis of myopericarditis was established, and then hospitalization was necessary. Clinical electrocardiographic settings and MRI are shown; EBV cardiac effects are discussed.

Likely tuberculous myocarditis mimicking an acute coronary syndrome.

Acute systemic infections may involve the heart, mostly represented by myocarditis and pericarditis. We report the case of a likely myopericarditis in an adult, leading to the diagnosis of tuberculosis infection. The clinical presentation was an acute coronary syndrome with elevated troponin Ic. An alternative diagnosis of myopericarditis was considered. Chest X-ray depicted a miliary pattern and a CT-scan demonstrated bilateral micronodules with a "tree-in-bud" pattern associated with parenchymal consolidations in the apical segment of the left upper lobe, suggesting infectious bronchiolitis. As the direct microscopic examination of the bronchial expectoration revealed the presence of Koch's bacterium, a diagnosis of a tuberculous myocarditis was likely. The clinical, electrocardiographic and CT-scan findings are shown; cardiac effects associated with tuberculosis are discussed.