Radiofrequency ablation lesions in low-, intermediate-, and normal-voltage myocardium: an in vivo study in a porcine heart model.

AIMS: Contact force (CF) between radiofrequency (RF) ablation catheter and myocardium and ablation index (AI) correlates with RF lesion depth and width in normal-voltage (>1.5 mV) myocardium (NVM). We investigate the impact of CF on RF lesion depth and width in low (<0.5 mV) (LVM) and intermediate-voltage (0.5-1.5 mV) myocardium (IVM) following myocardial infarction. Correlation between RF lesion depth and width evaluated by native contrast magnetic resonance imaging (ncMRI) and gross anatomical evaluation was investigated. METHODS AND RESULTS: Twelve weeks after myocardial infarction, 10 pigs underwent electroanatomical mapping and endocardial RF ablations were deployed in NVM, IVM, and LVM myocardium. In vivo ncMRI was performed before the heart was excised and subjected to gross anatomical evaluation. Ninety (82%) RF lesions were evaluated. Radiofrequency lesion depth and width were smaller in IVM and LVM compared with NVM (P < 0.001). Radiofrequency lesion depth and width correlated with CF, AI, and impedance drop in NVM (CF and AI P < 0.001) and IVM (CF and AI depths P < 0.001; CF and AI widths P < 0.05). Native contrast magnetic resonance imaging evaluated RF lesion depth and width correlated with gross anatomical depth and width (NVM and IVM P < 0.001; LVM P < 0.05). CONCLUSIONS: Radiofrequency lesions deployed by similar duration, power and CF are smaller in IVM and LVM than in NVM. Radiofrequency lesion depth and width correlated with CF, AI, and impedance drop in NVM and IVM but not in LVM. Native contrast magnetic resonance imaging may be useful to assess RF lesion depth and width in NVM, IVM, and LVM.

Multicenter Study of Ischemic Ventricular Tachycardia Ablation With Decrement-Evoked Potential (DEEP) Mapping With Extra Stimulus.

OBJECTIVES: The authors conducted a multicenter study of decrement-evoked potential (DEEP)-based functional ventricular tachycardia (VT) substrate modification to evaluate if such a mechanistic and physiological strategy is feasible and efficient in clinical practice and provides reduction in the VT burden. BACKGROUND: Only a fraction of the myocardium targeted in current VT substrate modification procedures is involved in the initiation and perpetuation of VT. The physiological basis of the DEEP strategy for identification of areas of initiation and maintenance of VT was recently established. METHODS: We included 20 consecutive patients with ischemic cardiomyopathy. During substrate mapping, fractionated and late potentials (LPs) were tagged, and an extra stimulus was performed to determine which LPs displayed decrement (DEEPs). All patients underwent DEEP-focused ablation: elimination of DEEP + further radiofrequency (RF) if VT was still inducible. Patients were followed during 6 months. RESULTS: Patients were predominantly male (95%), and their mean age was 64.6 ± 17.1 years. Mean left ventricular ejection fraction was 33.4 ± 11.4%. Mean ablation time was 30.6 ± 20.4 min. Specificity of DEEPs to detect the isthmus of VT was better than that of LPs (0.97 [95% confidence interval [CI]: 0.95 to 0.98] vs. 0.82 [95% CI: 0.73 to 0.89]), without significant differences in terms of sensitivity (0.61 [95% CI: 0.52 to 0.69] vs. 0.60 [95% CI: 0.44 to 0.74], respectively). Fifteen of 20 (75%) patients were free of any VT after DEEP-RF at 6 months of follow-up and there was a strong reduction in VT burden compared to 6 months pre-ablation. CONCLUSIONS: In a multicenter prospective study, DEEP substrate mapping identified the functional substrate critical to the VT circuit with high specificity. DEEP-guided VT ablation, by its physiological nature, may enable greater access to focused ablation therapy for patients requiring VT treatment.

S-25-hydroxyvitamin D and C3-epimers in pregnancy and infancy: An Odense Child Cohort study.

BACKGROUND: Analysis of serum 25-hydroxyvitamin D (s-25(OH)D) may be complicated by the less active or in-active vitamin D metabolite C3-epi-25(OH)D3 (C3-epimer). We aimed to explore the relationship between s-C3-epimer and s-25(OH)D and other determinants and describe the longitudinal course of the C3-epimer fraction in paired mother-child samples. METHOD: S-25(OH)D and s-C3-epimer were estimated by liquid chromatography mass spectrometry in 290 mother-infant pairs from the population-based Odense Child Cohort. Longitudinal analyses were feasible in two subcohorts; B) early and late pregnancy, cord, three and 18months (n=132); and C) early and late pregnancy, delivery and cord (n=105). RESULTS: Mean s-25(OH)D was 50.6-110.4nmol/L at the six time points. The mean C3-epimer fraction was 10.1% at three months, 1.1%-3.0% at the other time points. In multivariate analyses, the s-C3-epimer correlated with s-25(OH)D (all time points, p<0.001), and season, maternal and infant age and maternal vitamin D supplementation at some time points. The C3-epimer fraction fluctuated between adjacent time points. By cosinor analyses, a season-dependent sinusoidal pattern for s-25(OH)D and C3-epimer fraction was found and changes between adjacent time points depended on season (p<0.007 or trend). In early infancy, subtraction of the C3-epi-25(OH)D3 from total s-25(OH)D resulted in reclassification of 8% of the children by use of the 75nmol/L cut off for s-25(OH)D. CONLCUSION: The s-C3-epimer was independently correlated to s-25(OH)D, season, maternal vitamin D supplementation, maternal and infant age. The C3-epimer fraction was only of clinical importance in early infancy, where it could lead to misclassification of the vitamin D status.

Vitamin D supplementation, cord 25-hydroxyvitamin D and birth weight: Findings from the Odense Child Cohort.

BACKGROUND & AIMS: Hypovitaminosis D, defined as serum 25-hydroxyvitamin D (s-25(OH)D) <50 nmol/L, is frequent in pregnant women and neonates worldwide and has been associated with both low birth weight (BW) and placental weight (PW) as well as reduced placental development. We aimed to assess the prevalence and the risk factors of cord vitamin D deficiency (s-25(OH)D <25 nmol/L) and insufficiency (s-25(OH)D 25-50 nmol/L) and to evaluate the association between cord s-25(OH)D levels and neonatal outcomes (BW, PW and PW/BW ratio). METHODS: Women enrolled in Odense Child Cohort, a Danish observational prospective population-based cohort, who gave birth to singletons and donated a blood sample for s-25(OH)D measurements were included (n = 2082). RESULTS: The prevalence of cord vitamin D deficiency was 16.7% and 41.0% for insufficiency. White skin, winter season at birth, maternal supplementation dose of <15 µg/day, non-western ethnicity and high body mass index (BMI) were identified as independent risk factors of both vitamin D deficiency and insufficiency. Adherence to the recommended vitamin D supplementation dose (10 µg/day) was reported by 87% (primipara 91% vs. multipara 81%, p < 0.0001). An U-shaped relationship between cord s-25(OH)D and BW was visualized by spline regression (p = 0.003). After adjustment, cord s-25(OH)D was positively associated with BW (ß = 1.522, p = 0.026), PW (ß = 0.927, p < 0.001) and PW/BW ratio (ß = 0.018, p < 0.001), largely driven by positive associations for cord s-25(OH)D >60 nmol/L. CONCLUSION: Cord hypovitaminosis D was present in 57.7%. Multipara was identified as a novel risk factor of non-adherence to vitamin D supplementation recommendations; and a maternal supplementation dose <15 µg/day as a novel, independent risk factor of cord hypovitaminosis D. Higher BW, PW, and PW/BW ratio were associated to higher cord s-25(OH)D levels with a suggested cut-off at 60 nmol/L. More studies are encouraged to elucidate the impact of cord s-25(OH)D levels on offspring health and to establish optimal cut-offs for these outcomes.

Vitamin D insufficiency is associated with increased risk of first-trimester miscarriage in the Odense Child Cohort.

BACKGROUND: Miscarriage is the most common negative outcome of pregnancy, and identification of modifiable risk factors is potentially of great importance for public health. Low vitamin D concentrations in pregnancy are widespread worldwide, and vitamin D deficiency is implicated in immune cell regulation at the feto-maternal interface and several diseases of pregnancy. OBJECTIVE: We investigated whether 25-hydroxyvitamin D serum concentration was a modifiable risk factor for early miscarriage. DESIGN: In a prospective cohort study of 1683 pregnant women donating serum before gestational week 22, we investigated the association between maternal serum concentrations of serum 25-hydroxyvitamin D [25(OH)D] and the risk of subsequent miscarriage (n = 58). RESULTS: The adjusted hazard of first-trimester miscarriage was lower with higher 25(OH)D concentrations (HR: 0.98; 95% CI: 0.96, 0.99). Concentrations of 25(OH)D <50 nmol/L were associated with a >2-fold increased adjusted HR for miscarriage (HR: 2.50; 95% CI: 1.10, 5.69). Concentrations of 25(OH)D were not associated with an increased risk of second-trimester miscarriage. CONCLUSIONS: We found an association between 25(OH)D and first-trimester miscarriages, suggesting vitamin D as a modifiable risk factor for miscarriage. To test this hypothesis, randomized controlled trials should investigate the possible effect of vitamin D supplementation to increase 25(OH)D concentrations in early pregnancy, or before conception, to decrease risk of miscarriage. This trial was registered at clinicaltrials.gov as NCT02434900.

LA-ICP-MS-derived U-concentrations and microstructural domains within biogenic aragonite of Arctica islandica shell.

Understanding of the uranium uptake processes (both in vivo and post-mortem) into the skeletal structures of marine calcifiers is a subject of multi-disciplinary interest. U-concentration changes within the molluscan shell may serve as a paleoceanographic proxy of the pH history. A proxy of this type is needed to track the effects of fossil fuel emissions to ocean acidification. Moreover, attaining reliable U-series dates using shell materials would be a geochronological breakthrough. Picturing the high-resolution changes of U-concentrations in shell profiles is now possible by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Here, we analyzed in situ U-concentration variations in sub-fossilized shells of ocean quahog (Arctica islandica), a commonly studied bivalve species in Quaternary geoscience, using LA-ICP-MS. Microstructural details of the shell profiles were achieved by the scanning electron microscopy (SEM). Comparison of the shell aragonite microstructure with the changes in U-concentration revealed that uranium of possibly secondary origin is concentrated into the porous granular layers of the shell. Our results reinforce the hypothesis that U-concentration variations can be linked with microstructural differences within the shell. A combination of LA-ICP-MS and SEM analyses is recommended as an interesting approach for understanding the U-concentration variations in similar materials.

[Radiofrequency ablation therapy of intractable ventricular tachycardia present with a left ventricular assist device]. / Radiofrekvensablation af ventrikulær takykardi hos en patient med kunstig hjertepumpe.

Ventricular tachycardia (VT) occurs in up to 59% of patients with left ventricular assist devices (LVAD). In some of these patients, the VT cannot be managed medically or by implantable cardioverter-defibrillator. In this case, a 66-year-old male was successfully treated with radiofrequency ablation of intractable VT that developed months after implantation of an LVAD (Heartware). The LVAD provided haemodynamical support during mapping and did not interfere with the ablation.

The effects of cyclic guanylate cyclase stimulation on right ventricular hypertrophy and failure alone and in combination with phosphodiesterase-5 inhibition.

BACKGROUND: We investigated if soluble guanylate cyclase stimulation either alone or in combination with phosphodiesterase-5 (PDE5) inhibition could prevent pressure overload-induced right ventricular (RV) hypertrophy and failure. METHODS: The soluble guanylate cyclase stimulator BAY 41-2272 (BAY, 10 mg · kg⁻¹ · d⁻¹) either alone or in combination (BAY + SIL) with a PDE5 inhibitor sildenafil (SIL, 100 mg · kg⁻¹ · d⁻¹) was examined for prevention of RV hypertrophy and failure in Wistar rats (n = 73) operated by pulmonary trunk banding. RESULTS: All treatments failed to inhibit the development of RV hypertrophy and failure. In the BAY and BAY + SIL groups, there was an increased mortality. Mean arterial blood pressure was lowered and cardiac output increased in the BAY + SIL group. Systolic RV pressure was increased in the BAY and BAY + SIL groups possibly because of an inotropic response and/or increased venous return. CONCLUSIONS: Stimulation of soluble guanylate cyclase by BAY 41-2272 alone or in combination with sildenafil failed to prevent the development of RV hypertrophy and failure in rats subjected to pulmonary trunk banding. An increased mortality was observed in animals treated by BAY 41-2272 alone and in combination with sildenafil.