AimsThe most efficient way to acutely restore sinus rhythm from atrial fibrillation (AF) is electrical cardioversion, which is painful without adequate sedation. Recent studies in various... Show moreAimsThe most efficient way to acutely restore sinus rhythm from atrial fibrillation (AF) is electrical cardioversion, which is painful without adequate sedation. Recent studies in various experimental models have indicated that optogenetic termination of AF using light-gated ion channels may provide a myocardium-specific and potentially painless alternative future therapy. However, its underlying mechanism(s) remain(s) incompletely understood. As brief pulsed light stimulation, even without global illumination, can achieve optogenetic AF termination, besides direct conduction block also modulation of action potential (AP) properties may be involved in the termination mechanism. We studied the relationship between optogenetic AP duration (APD) and effective refractory period (ERP) prolongation by brief pulsed light stimulation and termination of atrial tachyarrhythmia (AT).Methods and resultsHearts from transgenic mice expressing the H134R variant of channelrhodopsin-2 in atrial myocytes were explanted and perfused retrogradely. AT induced by electrical stimulation was terminated by brief pulsed blue light stimulation (470 nm, 10 ms, 16 mW/mm2) with 68% efficacy. The termination rate was dependent on pulse duration and light intensity. Optogenetically imposed APD and ERP changes were systematically examined and optically monitored. Brief pulsed light stimulation (10 ms, 6 mW/mm2) consistently prolonged APD and ERP when light was applied at different phases of the cardiac action potential. Optical tracing showed light-induced APD prolongation during the termination of AT.ConclusionOur results directly demonstrate that cationic channelrhodopsin activation by brief pulsed light stimulation prolongs the atrial refractory period suggesting that this is one of the key mechanisms of optogenetic termination of AT. Show less
Hoogendoorn, J.C.; Venlet, J.; Out, Y.N.J.; Man, S.; Kumar, S.; Sramko, M.; ... ; Zeppenfeld, K. 2021
BACKGROUND Cardiac sarcoidosis (CS) with right ventricular (RV) involvement can mimic arrhythmogenic right ventricular cardiomyopathy (ARVC). Histopathological differences may result in disease... Show moreBACKGROUND Cardiac sarcoidosis (CS) with right ventricular (RV) involvement can mimic arrhythmogenic right ventricular cardiomyopathy (ARVC). Histopathological differences may result in disease-specific RV activation patterns detectable on the 12-lead electrocardiogram. Dominant subepicardial scar in ARVC leads to delayed activation of areas with reduced voltages, translating into terminal activation delay and occasionally (epsilon) waves with a small amplitude. Conversely, patchy transmural RV scar in CS may lead to conduction block and therefore late activated areas with preserved voltages reflected as preserved R' waves.OBJECTIVE The purpose of this study was to evaluate the distinct terminal activation patterns in precordial leads V-1 through V-3 as a discriminator between CS and ARVC.METHODS Thirteen patients with CS affecting the RV and 23 patients with gene-positive ARVC referred for ventricular tachycardia ablation were retrospectively included in a multicenter approach. A non-ventricular-paced 12-lead surface electrocardiogram was analyzed for the presence and the surface area of the R' wave (any positive deflection from baseline after an S wave) in leads V-1 through V-3.RESULTS An R' wave in leads V-1 through V-3 was present in all patients with CS compared to 11 (48%) patients with ARVC (P=.002). An algorithm including a PR interval of >= 220 ms, the presence of an R' wave, and the surface area of the maximum R' wave in leads V-1 through V-3 of similar to 1.65 mm(2) had 85% sensitivity and 96% specificity for diagnosing CS, validated in a second cohort (18 CS and 40 ARVC) with 83% sensitivity and 88% specificity.CONCLUSION An easily applicable algorithm including PR prolongation and the surface area of the maximum R' wave in leads V-1 through V-3 of similar to 1.65 mm(2) distinguishes CS from ARVC. This QRS terminal activation in precordial leads V-1 through V-3 may reflect disease-specific scar patterns. Show less
Riva, M. de; Naruse, Y.; Ebert, M.; Watanabe, M.; Scholte, A.J.; Wijnmaalen, A.P.; ... ; Zeppenfeld, K. 2021
Aims In patients with post-myocardial infarction (post-MI) ventricular tachycardia (VT), the presence of myocardial calcification (MC) may prevent heating of a subepicardial VT substrate... Show moreAims In patients with post-myocardial infarction (post-MI) ventricular tachycardia (VT), the presence of myocardial calcification (MC) may prevent heating of a subepicardial VT substrate contributing to endocardial ablation failure. The aims of this study were to assess the prevalence of MC in patients with post-MI VT and evaluate the impact of MC on outcome after endocardial ablation.Methods and results In 158 patients, the presence of MC was retrospectively assessed on fluoroscopy recordings in seven standard projections obtained during pre-procedural coronary angiograms. Myocardial calcification, defined as a distinct radiopaque area that moved synchronously with the cardiac contraction, was detected in 30 patients (19%). After endocardial ablation, only 6 patients (20%) with MC were rendered non-inducible compared with 56 (44%) without MC (P = 0.033) and of importance, 8 (27%) remained inducible for the clinical VT [compared with 9 (6%) patients without MC; P = 0.003] requiring therapy escalation. After a median follow-up of 31 months, 61 patients (39%) had VT recurrence and 47 (30%) died. Patients with MC had a lower survival free from the composite endpoint of VT recurrence or therapy escalation at 24-month follow-up (26% vs. 59%; P = 0.003). Presence of MC (HR 1.69; P = 0.046), a lower LV ejection fraction (HR 1.03 per 1% decrease; P = 0.017), and non-complete procedural success (HR 2.42; P = 0.002) were independently associated with a higher incidence of VT recurrence or therapy escalation.Conclusion Myocardial calcification was present in 19% of post-MI patients referred for VT ablation and was associated with a high incidence of endocardial ablation failure. Show less
Naruse, Y.; Riva, M. de; Watanabe, M.; Wijnmaalen, A.P.; Venlet, J.; Timmer, M.; ... ; Zeppenfeld, K. 2021
Background J-waves and fragmented QRS (fQRS) on surface ECGs have been associated with the occurrence of ventricular tachyarrhythmias. Whether these non-invasive parameters can also predict... Show moreBackground J-waves and fragmented QRS (fQRS) on surface ECGs have been associated with the occurrence of ventricular tachyarrhythmias. Whether these non-invasive parameters can also predict ventricular tachycardia (VT) recurrence after radiofrequency catheter ablation (RFCA) is unknown. Of interest, patients with a wide QRS-complex have been excluded from clinical studies on J-waves, although a J-wave like pattern has been described for wide QRS.Methods We retrospectively included 168 patients (67 +/- 10 years; 146 men) who underwent RFCA of post-infarct VT. J-wave pattern were defined as J-point elevation >= 0.1 mV in at least two leads irrespective of QRS width. fQRS was defined as various RSR` pattern in patients with narrow QRS and more than two R wave in those with wide QRS. The primary endpoint was VT recurrence after RFCA up to 24 months.Results J-wave pattern and fQRS were present in 27 and 28 patients, respectively. Overlap of J-wave pattern and fQRS was observed in nine. During a median follow-up of 20 (interquartile range 9-24) months, 46 (27%) patients had VT recurrence. Kaplan-Meier curves revealed that both J-wave pattern and fQRS were associated with VT recurrence. Multivariate Cox regression analysis demonstrated that the presence of J-wave pattern (hazard ratio [HR] 2.84; 95% confidence interval [CI] 1.45-5.58; P = .002) and greater number of induced VT (HR 1.29; 95% CI 1.15-1.45; P < .001) were the independent predictors of VT recurrence.Conclusions A J-wave pattern-but not fQRS-is independently associated with an increased risk of post-infarct VT recurrence after RFCA irrespective of QRS width. This simple non-invasive parameter may identify patients who require additional treatment. Show less
Elevated CO2 (eCO(2)) experiments provide critical information to quantify the effects of rising CO2 on vegetation 1-6 . Many eCO(2) experiments suggest that nutrient limitations modulate the local... Show moreElevated CO2 (eCO(2)) experiments provide critical information to quantify the effects of rising CO2 on vegetation 1-6 . Many eCO(2) experiments suggest that nutrient limitations modulate the local magnitude of the eCO(2) effect on plant biomass(1,3,5), but the global extent of these limitations has not been empirically quantified, complicating projections of the capacity of plants to take up CO27,9. Here, we present a data-driven global quantification of the eCO(2) effect on biomass based on 138 eCO(2) experiments. The strength of CO2 fertilization is primarily driven by nitrogen (N) in similar to 65% of global vegetation and by phosphorus (P) in similar to 25% of global vegetation, with N- or P-limitation modulated by mycorrhizal association. Our approach suggests that CO2 levels expected by 2100 can potentially enhance plant biomass by 12 +/- 3% above current values, equivalent to 59 +/- 13 PgC. The globalscale response to eCO(2) we derive from experiments is similar to past changes in greenness(9) and bio-mass(10) with rising CO2, suggesting that CO2 will continue to stimulate plant biomass in the future despite the constraining effect of soil nutrients. Our research reconciles conflicting evidence on CO2 fertilization across scales and provides an empirical estimate of the biomass sensitivity to eCO(2) that may help to constrain climate projections. Show less
Kece, F.; Scholte, A.J.; Riva, M. de; Naruse, Y.; Watanabe, M.; Alizadeh Dehnavi, R.; ... ; Trines, S.A. 2019
Background The posterior wall of the left atrium (LA) is a well-known substrate for atrial fibrillation (AF) maintenance. Isolation of the posterior wall between the pulmonary veins (box lesion)... Show moreBackground The posterior wall of the left atrium (LA) is a well-known substrate for atrial fibrillation (AF) maintenance. Isolation of the posterior wall between the pulmonary veins (box lesion) may improve ablation success. Box lesion surface area size varies depending on the individual anatomy. This retrospective study evaluates the influence of box lesion surface area as a ratio of total LA surface area (box surface ratio) on arrhythmia recurrence. Methods Seventy consecutive patients with persistent AF (63 +/- 11 years, 53 men) undergoing computed tomography (CT) imaging and ablation procedure consisting of a first box lesion were included in this study. Box lesion surface area was measured on electroanatomical maps and total LA surface area was derived from CT. Patients were followed with 24-h electrocardiography and exercise tests at 3, 6, and 12 months after AF ablation. Arrhythmia recurrence was defined as any AF/atrial tachycardia (AT) beyond 3 months without antiarrhythmic drugs. Results During a median follow-up of 13 (interquartile range = 10-17) months, 42 (60%) patients had AF/AT recurrence. Multivariate Cox proportional regression analysis showed that a larger box surface ratio protected against recurrence (hazard ratio [HR] = 0.81; 95% confidence interval [CI] = 0.690-0.955; P = 0.012). Left atrial volume index (HR = 1.01 [0.990-1.024, P = 0.427] and a history of mitral valve surgery (HR = 2.90; 95% CI = 0.970-8.693; P = 0.057) were not associated with AF recurrence in multivariate analysis. Conclusion A larger box lesion surface area as a ratio of total LA surface area is protective for AF/AT recurrence after ablation for persistent AF. Show less
We present the first near-IR scattered light detection of the transitional disk associated with the Herbig Ae star MWC 758 using data obtained as part of the Strategic Exploration of Exoplanets... Show moreWe present the first near-IR scattered light detection of the transitional disk associated with the Herbig Ae star MWC 758 using data obtained as part of the Strategic Exploration of Exoplanets and Disks with Subaru, and 1.1 {$μ$}m Hubble Space Telescope/NICMOS data. While submillimeter studies suggested there is a dust-depleted cavity with r = 0.''35, we find scattered light as close as 0.''1 (20-28 AU) from the star, with no visible cavity at H, K', or K$_s$ . We find two small-scaled spiral structures that asymmetrically shadow the outer disk. We model one of the spirals using spiral density wave theory, and derive a disk aspect ratio of h ~{} 0.18, indicating a dynamically warm disk. If the spiral pattern is excited by a perturber, we estimate its mass to be 5$^{+3}$ $_{- 4}$ M$_J$ , in the range where planet filtration models predict accretion continuing onto the star. Using a combination of non-redundant aperture masking data at L' and angular differential imaging with Locally Optimized Combination of Images at K' and K$_s$ , we exclude stellar or massive brown dwarf companions within 300 mas of the Herbig Ae star, and all but planetary mass companions exterior to 0.''5. We reach 5{$σ$} contrasts limiting companions to planetary masses, 3-4 M$_J$ at 1.''0 and 2 M$_J$ at 1.''55, using the COND models. Collectively, these data strengthen the case for MWC 758 already being a young planetary system. Show less
Grady, C.; Muto, T.; Hashimoto, J.; Fukagawa, M.; Currie, T.; Biller, B.; ... ; Tamura, M. 2013
We present the first near-IR scattered light detection of the transitional disk associated with the Herbig Ae star MWC 758 using data obtained as part of the Strategic Exploration of Exoplanets and... Show moreWe present the first near-IR scattered light detection of the transitional disk associated with the Herbig Ae star MWC 758 using data obtained as part of the Strategic Exploration of Exoplanets and Disks with Subaru, and 1.1 {$μ$}m Hubble Space Telescope/NICMOS data. While submillimeter studies suggested there is a dust-depleted cavity with r = 0.''35, we find scattered light as close as 0.''1 (20-28 AU) from the star, with no visible cavity at H, K', or K$_s$ . We find two small-scaled spiral structures that asymmetrically shadow the outer disk. We model one of the spirals using spiral density wave theory, and derive a disk aspect ratio of h ~{} 0.18, indicating a dynamically warm disk. If the spiral pattern is excited by a perturber, we estimate its mass to be 5$^{+3}$ $_{- 4}$ M$_J$ , in the range where planet filtration models predict accretion continuing onto the star. Using a combination of non-redundant aperture masking data at L' and angular differential imaging with Locally Optimized Combination of Images at K' and K$_s$ , we exclude stellar or massive brown dwarf companions within 300 mas of the Herbig Ae star, and all but planetary mass companions exterior to 0.''5. We reach 5{$σ$} contrasts limiting companions to planetary masses, 3-4 M$_J$ at 1.''0 and 2 M$_J$ at 1.''55, using the COND models. Collectively, these data strengthen the case for MWC 758 already being a young planetary system. Show less
D'Haens, G.R.; Panaccione, R.; Higgins, P.D.R.; Vermeire, S.; Gassull, M.; Chowers, Y.; ... ; Travis, S. 2011
The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical... Show moreThe advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability, reimbursement guidelines, and patient preferences guide the choice of first-line biological therapy for luminal Crohn's disease (CD). Infliximab (IFX) has the most extensive clinical trial data, but other biological agents (adalimumab (ADA), certolizumab pegol (CZP), and natalizumab (NAT)) appear to have similar benefits in CD. Steroid-refractory, steroid-dependent, or complex fistulizing CD are indications for starting biological therapy, after surgical drainage of any sepsis. For fistulizing CD, the efficacy of IFX for inducing fistula closure is best documented. Unique risks of NAT account for its labeling as a second-line biological agent in some countries. Patients who respond to induction therapy benefit from systematic re-treatment. The combination of IFX with azathioprine is better than monotherapy for induction of remission and mucosal healing up to 1 year in patients who are naive to both agents. Whether this applies to other agents remains unknown. IFX is also effective for treatment-refractory, moderate, or severely active ulcerative colitis. Patients who have a diminished or loss of response to anti-tumor necrosis factor (TNF) therapy may respond to dose adjustment of the same agent or switching to another agent. Careful consideration should be given to the reasons for loss of response. There are insufficient data to make recommendations on when to stop anti-TNF therapy. Preliminary evidence suggests that a substantial proportion of patients in clinical remission for > 1 year, without signs of active inflammation can remain in remission after stopping treatment. Show less
