Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a difficult-to-diagnose cause of sudden cardiac death (SCD). We identified a family of 1400 individuals with multiple cases of CPVT, ...including 36 SCDs during youth.
We sought to identify the genetic cause of CPVT in this family, to preventively treat and clinically characterize the mutation-positive individuals, and to functionally characterize the pathogenic mechanisms of the mutation.
Genetic testing was performed for 1404 relatives. Mutation-positive individuals were preventively treated with β-blockers and clinically characterized with a serial exercise treadmill test (ETT) and Holter monitoring. In vitro functional studies included caffeine sensitivity and store overload-induced calcium release activity of the mutant channel in HEK293 cells.
We identified the p.G357S_RyR2 mutation, in the cardiac ryanodine receptor, in 179 family members and in 6 SCD cases. No SCD was observed among treated mutation-positive individuals over a median follow-up of 37 months; however, 3 relatives who had refused genetic testing (confirmed mutation-positive individuals) experienced SCD. Holter monitoring did not provide relevant information for CPVT diagnosis. One single ETT was unable to detect complex cardiac arrhythmias in 72% of mutation-positive individuals, though the serial ETT improved the accuracy. Functional studies showed that the G357S mutation increased caffeine sensitivity and store overload-induced calcium release activity under conditions that mimic catecholaminergic stress.
Our study supports the use of genetic testing to identify individuals at risk of SCD to undertake prophylactic interventions. We also show that the pathogenic mechanisms of p.G357S_RyR2 appear to depend on β-adrenergic stimulation.
...it may be that post-procedure VT inducibility could simply be a marker of a worse prognosis, reflecting differences in scar extension and transmurality. ...the analysis is performed by comparing 2 ...rather artificial and unbalanced groups of patients:
The development of complete AV block and the need for pacemaker implantation (PM) is the most frequent complication after Transaortic valve replacement (TAVR). In other PM clinical contexts, a higher ...percentage of ventricular stimulation has been associated with worse prognosis. The objective was to study the existence of predictors of PM dependence.
We identified 96 consecutive patients who had received a PM post-TAVR (all Core-Valve). We retrospectively analyzed this cohort with the aim of identifying predictors of a high and very high percentage of ventricular pacing (VP), PM dependency and survival.
The mean age was 82.3 years, with a mean logistic EuroSCORE of 17.1, 53% were women and 12% of patients had LVEF < 50%. The indication was complete AV block in 40.5%, and LBBB in 59.5%. Mean survival was 62.7 months, IQR 54.4–71. The only independent predictor of mortality was the pre-TAVR logistic Euro-SCORE (RR = 1,026, p = 0.033), but not LVEF < 50%, VP > 50%, VP > 85% or PM dependence. In 73 patients PM rhythm was documented at the end of follow-up. Of these, 14 (19.2%) were considered dependent, and 37 (50.7%) presented VP > 50%. The post-TAVR complete AV block recovery rate was 67.8%. In multivariate analysis, female sex (HR = 5.6, p = 0.005), and indication of complete AV block vs. LBBB (HR = 15.7, p = 0.017) were independently associated with PM dependency.
Female sex and indication due to complete AV block were independent predictors of PM dependency during follow up. In our series of patients with mostly normal LVEF, a high percentage of stimulation does not influence prognosis.
Clinical data suggest that cardiosphere-derived cells (CDCs) could modify post-infarction scar and ventricular remodeling and reduce the incidence of ventricular tachycardia (VT). This paper assesses ...the effect of CDCs on VT substrate in a pig model of postinfarction monomorphic VT. We studied the effect of CDCs on the electrophysiological properties and histological structure of dense scar and heterogeneous tissue (HT). Optical mapping and histological evaluation were performed 16 weeks after the induction of a myocardial infarction by transient occlusion of the left anterior descending (LAD) artery in 21 pigs. Four weeks after LAD occlusion, pigs were randomized to receive intracoronary plus trans-myocardial CDCs (IC+TM group, n: 10) or to a control group. Optical mapping (OM) showed an action potential duration (APD) gradient between HT and normal tissue in both groups. CDCs increased conduction velocity (53 ± 5 vs. 45 ± 6 cm/s, p < 0.01), prolonged APD (280 ± 30 ms vs. 220 ± 40 ms, p < 0.01) and decreased APD dispersion in the HT. During OM, a VT was induced in one and seven of the IC+TM and control hearts (p = 0.03), respectively; five of these VTs had their critical isthmus located in intra-scar HT found adjacent to the coronary arteries. Histological evaluation of HT revealed less fibrosis (p < 0.01), lower density of myofibroblasts (p = 0.001), and higher density of connexin-43 in the IC+TM group. Scar and left ventricular volumes did not show differences between groups. Allogeneic CDCs early after myocardial infarction can modify the structure and electrophysiology of post-infarction scar. These findings pave the way for novel therapeutic properties of CDCs.
Permafrost controls geomorphic processes in ice-free areas of the Antarctic Peninsula (AP) region. Future climate trends will promote significant changes of the active layer regime and permafrost ...distribution, and therefore a better characterization of present-day state is needed. With this purpose, this research focuses on Ulu Peninsula (James Ross Island) and Byers Peninsula (Livingston Island), located in the area of continuous and discontinuous permafrost in the eastern and western sides of the AP, respectively. Air and ground temperatures in as low as 80 cm below surface of the ground were monitored between January and December 2014. There is a high correlation between air temperatures on both sites (r=0.74). The mean annual temperature in Ulu Peninsula was -7.9 ºC, while in Byers Peninsula was -2.6 ºC. The lower air temperatures in Ulu Peninsula are also reflected in ground temperatures, which were between 4.9 (5 cm) and 5.9 ºC (75/80 cm) lower. The maximum active layer thickness observed during the study period was 52 cm in Ulu Peninsula and 85 cm in Byers Peninsula. Besides climate, soil characteristics, topography and snow cover are the main factors controlling the ground thermal regime in both areas.
IntroductionPost myocardial infarction (MI) patients are at risk of scar related ventricular tachycardia (VT).HypothesisStem cell therapy reduces post-MI scar size, potentially leading to a reduction ...in the risk of ventricular arrhythmias (VA).MethodsA post-MI scar model of VT was created by transient occlusion of the mid left anterior descending artery in 56 swine. Five weeks after infarct creation 29 subjects were treated with allogeneic cardiac stem cells (CSC)10 underwent transcoronary delivery of CSC, 9 direct transepicardial delivery (via a minithoracotomy) and 10 underwent a combined transcoronary and VT substrate guided (late potentials) direct transendocardial CSC delivery procedure using an electroanatomic mapping system. Of the remainder, 8 subjects underwent a “sham” transepicardial procedure and 19 served as controls. Seventeen weeks after infarct creation an electrophysiological study was performed in each subject to assess for ventricular arrhythmia inducibility. VA inducibility was compared in each group vs. the control group.ResultsOf the 19 control subjects, 17 were inducible (89,5 %). As presented in the figure, CSC delivery with a combined transcoronary/transendocardial approach was associated with a significant reduction in VT inducibility rates compared to controls (20 % vs. 89,5 %; p value 0,001). Subjects treated with transcoronary CSC also experienced significantly lower VA inducibility rates (40 % vs. 89,5 %; p value 0,009). There were no differences in VA inducibility compared with controls in patients in the “sham” (62,5 % vs 89,5 %; p value 0,136) or the transepicardial group (66,7 % vs 89,5 %; p value 0,290).ConclusionsCombined transcoronary and VT substrate-guided transendocardial CSC delivery is associated with a significant reduction in VA inducibility in a post-MI swine model. Future human studies should evaluate the effects of allogeneic CSC therapy on ventricular arrhythmia burden in post-MI patients.
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