Characterization of the electrophysiological substrate in patients with Barlow's disease.

BACKGROUND: Myxomatous mitral valve prolapse (MVP) and mitral-annular disjunction (Barlow disease) are at-risk for ventricular arrhythmias (VA). Fibrosis involving the papillary muscles and/or the infero-basal left ventricular (LV) wall was reported at autopsy in sudden cardiac death (SCD) patients with MVP. OBJECTIVES: We investigated the electrophysiological substrate subtending VA in MVP patients with Barlow disease phenotype. METHODS: Twenty-three patients with VA were enrolled, including five with syncope and four with a history of SCD. Unipolar (Uni < 8.3 mV) and bipolar (Bi < 1.5 mV) low-voltage areas were analyzed with electro-anatomical mapping (EAM), and VA inducibility was evaluated with programmed ventricular stimulation (PES). Electrophysiological parameters were correlated with VA patterns, electrocardiogram (ECG) inferior negative T wave (nTW), and late gadolinium enhancement (LGE) assessed by cardiac magnetic resonance. RESULTS: Premature ventricular complex (PVC) burden was 12 061.9 ± 12 994.6/24 h with a papillary-muscle type (PM-PVC) in 18 patients (68%). Twelve-lead ECG showed nTW in 12 patients (43.5%). A large Uni less than 8.3 mV area (62.4 ± 45.5 cm2 ) was detected in the basal infero-lateral LV region in 12 (73%) patients, and in the papillary muscles (2.2 ± 2.9 cm2 ) in 5 (30%) of 15 patients undergoing EAM. A concomitant Bi less than 1.5 mV area (5.0 ± 1.0 cm2 ) was identified in two patients. A history of SCD, and the presence of nTW, and LGE were associated with a greater Uni less than 8.3 mV extension: (32.8 ± 3.1 cm2 vs. 9.2 ± 8.7 cm2 ), nTW (20.1 ± 11.0 vs. 4.1 ± 3.8 cm2 ), and LGE (19.2 ± 11.7 cm2 vs. 1.0 ± 2.0 cm2 , p = .013), respectively. All patients with PM-PVC had a Uni less than 8.3 mV area. Sustained VA (ventricular tachycardia 2 and VF 2) were induced by PES only in four patients (one with resuscitated SCD). CONCLUSIONS: Low unipolar low voltage areas can be identified with EAM in the basal inferolateral LV region and in the papillary muscles as a potential electrophysiological substrate for VA and SCD in patients with MVP and Barlow disease phenotype.

Dynamic changes of mitral valve annulus geometry at preprocedural CT: relationship with functional classes of regurgitation.

BACKGROUND: We investigated mitral valve annular geometry changes during the cardiac cycle in patients with severe mitral regurgitation (MR) who underwent cardiac computed tomography angiography (CCTA) prior to percutaneous mitral valve replacement or annuloplasty. METHODS: Fifty-one patients with severe MR and high surgical risk (Carpentier classification: 3 type I, 16 type II, 16 type IIIa, 16 type IIIb) underwent multiphase electrocardiographically gated (0-90%) CCTA, using a second generation dual-source CT scanner, as pre-procedural planning. Twenty-one patients without MR served as controls. The mitral valve annulus was segmented every 10% step of the R-R interval, according to the D-shaped segmentation model, and differences among groups were analysed by t-test or ANOVA. RESULTS: Mitral annular area and diameters were larger in MR patients compared to controls, particularly in type II. Mitral annular area varied in MR patients throughout the cardiac cycle (mean ± standard deviation of maximum and minimum area 15.6 ± 3.9 cm2 versus 13.0 ± 3.5 cm2, respectively; p = 0.001), with greater difference between annular areas versus controls (2.59 ± 1.61 cm2 and 1.98 ± 0.6 cm2, p < 0.001). The largest dimension was found in systolic phases (20-40%) in most of MR patients (n = 27, 53%), independent of Carpentier type (I: n = 1, 33%; II: n = 10, 63%; IIIa: n = 8, 50%; IIIb: n = 8, 50%), and in protodiastolic phases (n = 14, 67%) for the control group. CONCLUSIONS: In severe MR, mitral annular area varied significantly throughout the cardiac cycle, with a tendency towards larger dimensions in systole.

Validation of an Accurate and Noninvasive Tool to Exclude Female Precocious Puberty: Pelvic Ultrasound With Uterine Artery Pulsatility Index.

OBJECTIVE. The purpose of this study is to validate the accuracy of pelvic ultrasound (US) with the evaluation of uterine artery pulsatility index (PI) to exclude female precocious puberty. MATERIALS AND METHODS. Tanner breast development score, luteinizing hormone (LH) peak after gonadotropin-releasing hormone (GnRH) stimulation, and uterine and ovarian volumes and diameters were assessed with pelvic US in 495 girls at a single institution. The study population was divided as follows: prepubertal (n = 207), pubertal with physiologic activation of the hypothalamic-pituitary-ovarian axis (n = 176), and central precocious puberty (CPP; n = 112). PI was measured with spectral Doppler US at the ascending branches of the right uterine artery (50-Hz filter; time gain compensation, 73; pulse repetition frequency, 6.6). ROC analyses and t tests were performed. RESULTS. The mean (± SD) PI values in the prepubertal, pubertal, and CPP groups were 6.3 ± 1.4, 3.4 ± 1.1, and 4.1 ± 1.5, respectively (p < 0.001). The best PI cutoff value to distinguish pubertal from prepubertal girls was 4.6 (sensitivity, 83%; specificity, 94%; positive predictive value, 95%; negative predictive value, 80%; accuracy, 87%). ROC AUC values for LH peak (cutoff value, 5 mU/mL) and for spectral Doppler US PI plus longitudinal uterine diameter (i.e., the combination of a PI of 4.6 with a longitudinal uterine diameter of 35 mm) were 0.9272 and 0.9439, respectively (p = 0.7925). The negative predictive values for LH peak and for PI plus longitudinal uterine diameter were 89% and 88%, respectively. CONCLUSION. A PI greater than 4.6 at spectral Doppler US combined with a longitudinal uterine diameter less than 35 mm allows noninvasive exclusion of female precocious puberty with comparable accuracy and lower costs compared to examination of LH peak after GnRH stimulation. Therefore, PI plus longitudinal uterine diameter might be used as a noninvasive first-line test to exclude precocious puberty and thereby avoid further investigations.

Assessment of Remote Myocardium Heterogeneity in Patients with Ventricular Tachycardia Using Texture Analysis of Late Iodine Enhancement (LIE) Cardiac Computed Tomography (cCT) Images.

PURPOSE: Diffuse remodeling of myocardial extra-cellular matrix is largely responsible for left ventricle (LV) dysfunction and arrhythmias. Our hypothesis is that the texture analysis of late iodine enhancement (LIE) cardiac computed tomography (cCT) images may improve characterization of the diffuse extra-cellular matrix changes. Our aim was to extract volumetric extracellular volume (ECV) and LIE texture features of non-scarred (remote) myocardium from cCT of patients with recurrent ventricular tachycardia (rVT), and to compare these radiomic features with LV-function, LV-remodeling, and underlying cardiac disease. PROCEDURES: Forty-eight patients suffering from rVT were prospectively enrolled: 5/48 with idiopathic VT (IVT), 23/48 with post-ischemic dilated cardiomyopathy (ICM), 9/48 with idiopathic dilated cardiomyopathy (IDCM), and 11/48 with scars from a previous healed myocarditis (MYO). All patients underwent echocardiography to assess LV systolic and diastolic function and cCT with pre-contrast, angiographic, and LIE scan to obtain end-diastolic volume (EDV), ECV, and first-order texture parameters of Hounsfield Unit (HU) of remote myocardium in LIE [energy, entropy, HU-mean, HU-median, standard deviation (SD), and mean absolute deviation (MAD)]. RESULTS: Energy, HU mean, and HU median by cCT texture analysis correlated with ECV (rho = 0.5650, rho = 0.5741, rho = 0.5068; p < 0.0005). cCT-derived ECV, HU-mean, HU-median, SD, and MAD correlated directly to EDV by cCT and inversely to ejection fraction by echocardiography (p < 0.05). SD and MAD correlated with diastolic function by echocardiography (rho = 0.3837, p = 0.0071; rho = 0.3330, p = 0.0208). MYO and IVT patients were characterized by significantly lower values of SD and MAD when compared with ICM and IDCM patients, independently of LV-volume systolic and diastolic function. CONCLUSIONS: Texture analysis of LIE may expand cCT capability of myocardial characterization. Myocardial heterogeneity (SD and MAD) was associated with LV dilatation, systolic and diastolic function, and is able to potentially identify the different patterns of structural remodeling characterizing patients with rVT of different etiology.

Single-centre experience of extending indications for percutaneous intraportal islet autotransplantation (PIPIAT) after pancreatic surgery to prevent diabetes: feasibility, radiological aspects, complications and clinical outcome.

OBJECTIVE: Islet allotransplantation is a less invasive alternative to surgical pancreas transplantation for Type 1 diabetes, while percutaneous intraportal islet autotransplantation (PIPIAT) is usually performed after pancreatic surgery to prevent diabetes. Our aim was to assess the feasibility, radiological aspects, complications and clinical outcome of PIPIAT following pancreatic surgery for not only chronic pancreatitis but also benign and malignant nodules. METHODS: From 2008 to 2012, 41 patients were enrolled for PIPIAT 12-48 h after pancreatic surgery (extended pancreatic surgery for chronic pancreatitis and benign/malignant neoplasms). PIPIAT was performed using a combined ultrasonography and fluoroscopy-guided technique (4-F catheter). PIPIAT feasibility, median follow-up and metabolic (insulin independence rate, graft function based on C-peptide levels) and oncologic outcomes were recorded. RESULTS: PIPIAT was not performed in 7/41 patients (4 cases for an inadequate islet mass, 2 cases for haemodynamic instability and 1 case for islet culture contamination), while it was successfully performed in 34/34 patients. Procedure-related major complications occurred in four patients: two bleedings requiring transfusions, one patient with left portal vein thrombosis and one patient with sepsis. Median follow-up duration was 546 days. Insulin independence was achieved in 15/34 (44%) patients, partial graft function in 16/34 (47%) patients and no function in 3/34 (9%) patients. None of the 17 patients with malignant nodules developed liver metastases during follow-up. CONCLUSION: PIPIAT, performed under ultrasound and fluoroscopy combined guidance and not requiring immunosuppression, is feasible, with a relatively low complication rate and a better metabolic outcome than allotransplantation. ADVANCES IN KNOWLEDGE: PIPIAT can prevent pancreatogenic diabetes. Ultrasound is a useful tool for the guidance and monitoring of PIPIAT.

Cardiac CT With Delayed Enhancement in the Characterization of Ventricular Tachycardia Structural Substrate: Relationship Between CT-Segmented Scar and Electro-Anatomic Mapping.

OBJECTIVES: This study sought to compare myocardial scars depicted by computed tomography (CT) with electrical features from electro-anatomic mapping (EAM), assessing the potential role of CT integration in ventricular tachycardia (VT) and radiofrequency catheter ablation (RFCA) procedures. BACKGROUND: Imaging-based characterization of VT myocardial substrate is required to plan EAM and, potentially, to guide RFCA. METHODS: Forty-two consecutive patients, 35 of whom had implantable cardioverter-defibrillator, all referred for VT RFCA, underwent pre-procedural CT including an angiographic and a 10-min delayed-enhancement scan. Segmental comparison between scars segmented from CT and low voltages (bipolar voltages <1.5 mV; unipolar voltages <8 mV), late potentials, and RF ablation points on EAM, was carried out. In a subset of 16 consecutive patients, a further point-by-point analysis was performed: a CT-derived 3-dimensional structure including heart anatomy and myocardial scars was integrated with EAM for quantitative comparison. RESULTS: CT scans identified scars in 39 patients and defined left ventricular wall involvement and mural distribution. Overall segmental concordance between CT and EAM was good (κ = 0.536) despite the presence of implantable cardioverter-defibrillator, scar etiologies, and mural distribution. CT identified segments characterized by low voltages with good sensitivity (76%), good specificity (86%), and very high negative predictive value (95%). Late potentials and RF ablation points fell on scarred segments identified from CT in 79% and 81% of cases, respectively. Point-by-point quantitative comparison revealed good correlation between the average area of scar detected at CT and at bipolar mapping (CT = 4,901 mm(2), bipolar voltages-EAM = 4,070 mm(2); R = 0.78; p < 0.0001). In this study, 70% and 84% of low-amplitude bipolar points were mapped at a maximum distance of 5 mm and 10 mm from CT-segmented scar, respectively. CONCLUSIONS: CT with delayed-enhancement provides a 3-dimensional characterization of VT scar substrate together with a detailed anatomic model of the heart. This information may offer assistance to plan EAM and RFCA procedures and is potentially suitable for EAM-imaging integration.

Cardiac Multi-detector CT Segmentation Based on Multiscale Directional Edge Detector and 3D Level Set.

Extraction of the cardiac surfaces of interest from multi-detector computed tomographic (MDCT) data is a pre-requisite step for cardiac analysis, as well as for image guidance procedures. Most of the existing methods need manual corrections, which is time-consuming. We present a fully automatic segmentation technique for the extraction of the right ventricle, left ventricular endocardium and epicardium from MDCT images. The method consists in a 3D level set surface evolution approach coupled to a new stopping function based on a multiscale directional second derivative Gaussian filter, which is able to stop propagation precisely on the real boundary of the structures of interest. We validated the segmentation method on 18 MDCT volumes from healthy and pathologic subjects using manual segmentation performed by a team of expert radiologists as gold standard. Segmentation errors were assessed for each structure resulting in a surface-to-surface mean error below 0.5 mm and a percentage of surface distance with errors less than 1 mm above 80%. Moreover, in comparison to other segmentation approaches, already proposed in previous work, our method presented an improved accuracy (with surface distance errors less than 1 mm increased of 8-20% for all structures). The obtained results suggest that our approach is accurate and effective for the segmentation of ventricular cavities and myocardium from MDCT images.

Preliminary results of contrast-enhanced sonography in the evaluation of the response of uveal melanoma to gamma-knife radiosurgery.

PURPOSE: Our aim was to prospectively analyze the use of contrast-enhanced ultrasound (CEUS) in the quantitative assessment of the response of uveal melanoma (UM) to gamma-knife radiosurgery (GKR), investigating whether changes in tumor vascularization precede thickness reduction, which on average occurs at 12 months after GKR. METHODS: Ten patients with UM treated with GKR underwent sonography (US) and CEUS at baseline and at 3, 6, and 12 months after GKR. The transverse diameter, thickness, and quantitative parameters of the UM (ie, area under the curve in the wash-in phase, wash-in perfusion index, peak enhancement, and wash-in rate) were calculated by using dedicated software and compared by using Wilcoxon's signed-rank test. RESULTS: The mean tumor thickness on US was significantly less at both 6 (6.6 mm) and 12 months after GKR (5.8 mm) than it was at baseline (8.3 mm; p < 0.05, both comparisons). Compared with baseline data, the median flow quantitative parameters on CEUS were significantly changed as follows: the peak enhancement (in arbitrary units [au]) at baseline was 5 × 10(6) ; 6 months after GKR, it was 2 × 10(1) (p < 0.05), and 12 months after GKR, it was 4 × 10(1) (p < 0.05). The wash-in rate (in au) at baseline was 1 × 10(6) ; 6 months after GKR, it was 2.1 (p < 0.05), and 12 months after GKR, it was 9.3 (p < 0.05). The wash-in perfusion index (in au) at baseline was 2 × 10(7) ; 6 months after GKR, it was 7 × 10(1) (p < 0.05), and 12 months after GKR, it was 1 × 10(2) (p < 0.05). The area under the curve during the wash-in phase (in au) at baseline was 1 × 10(8) ; 12 months after GKR, it was reduced to 6 × 10(2) (p < 0.05). CONCLUSIONS: At 6 months after GKR, a reduction of tumor thickness, as detected on US, occurred in 6 of the 10 patients, whereas a reduction in all the quantitative parameters measured on CEUS occurred in all 10 patients. However, a larger population is needed to investigate whether CEUS could become the first-choice technique for monitoring the response of UM to GKR.

Imaging and epicardial substrate ablation of ventricular tachycardia in patients late after myocarditis.

AIMS: We present clinical, electroanatomical mapping (EAM), imaging, and catheter ablation (CA) strategies in patients with myocarditis-related ventricular tachycardia (VT). METHODS AND RESULTS: Between January 2010 and July 2012, 26 consecutive patients underwent imaging-guided CA of myocarditis-related ventricular arrhythmias, 23 of 26 using a combined endo-epicardial approach. Segment per segment correspondence of late enhanced (LE) scar localization with EAM scar was assessed in all patients with available uni/bipolar maps (n = 19). Induced VTs were targeted prior to substrate modification. Late potentials (LPs) abolition constituted a procedural endpoint independently from VT inducibility. Clinical monomorphic VT was induced in 15 of 26 patients (57.7%) and was associated with epicardial LPs in 10 of 15, completely abolished in 7 of 10 patients. Of the 10 patients rendered non-inducible VTs were ablated epicardially in 7. Late potentials were also detected in 7 of 11 initially non-inducible patients and completely abolished in 4. After a median follow-up of 23 (15-31) months, 20 of 26 patients (76.9%) remained free from VT recurrence. Bipolar mapping revealed low-voltage scar (<1.5 mV) in 1 patient endocardially and in 14 of 19 epicardially. Unipolar mapping revealed low-voltage scar (<8 mV) in 12 of 19 patients endocardially and in 18 of 19 epicardially. Correspondence of LE scar localization with endocardial bipolar scar was 1%, with endocardial unipolar scar 23.7%, with epicardial bipolar scar 39.8%, and with epicardial unipolar scar 66.2%. CONCLUSION: Pre-procedural scar imaging and EAM findings support the necessity of an epicardial approach in patients with prior myocarditis. Epicardial unipolar mapping (<8 mV) is superior in scar identification and CA based on substrate modification is safe and effective in this setting.

Multidetector computed tomography for coronary stents imaging: high-voltage (140-kVp) prospective ECG-triggered versus standard-voltage (120-kVp) retrospective ECG-gated helical scanning.

OBJECTIVE: To compare prospective electrocardiogram (ECG)-triggered high-voltage coronary computed tomography (CT) angiography (CTA; 140-kVp P-cCTA) with retrospective ECG-gated standard-voltage cCTA (120-kVp R-cCTA), in patients with coronary stents. METHODS: Fifty-two patients with coronary stents were studied with 64-slice multidetector scanner. Ninety-three stents were analyzed: 55 with 140-kVp P-cCTA and 38 with 120-kVp R-cCTA. Image quality (IQ), diagnostic confidence (DC), in-stent assessable lumen, artificial narrowing, and effective radiation dose were compared between techniques. RESULTS: Image quality and DC were significantly better for the 140-kVp P-cCTA in comparison with the 120-kVp R-cCTA (IQ, 1.1 ± 0.36 vs 1.7 ± 0.60, respectively; P < 0.00001. Diagnostic confidence: 1.1 ± 0.29 vs 1.5 ± 0.65 respectively; P < 0.0001). In-stent assessable lumen and artificial narrowing were comparable between the techniques. Effective dose was lower for the 140-kVp P-cCTA (6.7 ± 2.07 mSv vs 15.8 ± 6.89 mSv; P < 0.0001). CONCLUSIONS: High voltage combined with axial prospective ECG-triggered scan improved IQ and DC in stent cCTA imaging but failed to improve the diameter of in-stent assessable lumen and to reduce the artificial narrowing compared with the 120-kVp R-cCTA. Effective dose was 60% lower for the 140-kVp P-cCTA.

Magnetic resonance imaging at 7T reveals common events in age-related sarcopenia and in the homeostatic response to muscle sterile injury.

Skeletal muscle remodeling in response to various noxae physiologically includes structural changes and inflammatory events. The possibility to study those phenomena in-vivo has been hampered by the lack of validated imaging tools. In our study, we have relied on multiparametric magnetic resonance imaging for quantitative monitoring of muscle changes in mice experiencing age-related sarcopenia or active regeneration after sterile acute injury of tibialis anterior muscle induced by cardiotoxin (CTX) injection. The extent of myofibrils' necrosis, leukocyte infiltration, and regeneration have been evaluated and compared with parameters from magnetic resonance imaging: T2-mapping (T2 relaxation time; T2-rt), diffusion-tensor imaging (fractional anisotropy, F.A.) and diffusion weighted imaging (apparent diffusion coefficient, ADC). Inflammatory leukocytes within the perimysium and heterogeneous size of fibers characterized aged muscles. They displayed significantly increased T2-rt (P<0.05) and F.A. (P<0.05) compared with young muscles. After acute damage T2-rt increased in otherwise healthy young muscles with a peak at day 3, followed by a progressive decrease to basal values. F.A. dropped 24 hours after injury and afterward increased above the basal level in the regenerated muscle (from day 7 to day 15) returning to the basal value at the end of the follow up period. The ADC displayed opposite kinetics. T2-rt positively correlated with the number of infiltrating leucocytes retrieved by immunomagnetic bead sorting from the tissue (r = 0.92) and with the damage/infiltration score (r = 0.88) while F.A. correlated with the extent of tissue regeneration evaluated at various time points after injury (r = 0.88). Our results indicate that multiparametric MRI is a sensitive and informative tool for monitoring inflammatory and structural muscle changes in living experimental animals; particularly, it allows identifying the increase of T2-rt and F.A. as common events reflecting inflammatory infiltration and muscle regeneration in the transient response of the tissue to acute injury and in the persistent adaptation to aging.

Gender influence on dose saving allowed by prospective-triggered 64-slice multidetector computed tomography coronary angiography as compared with retrospective-gated mode.

BACKGROUND/OBJECTIVES: To assess the gender influence on radiation dose saving allowed by prospective ECG-triggered MDCT coronary angiography (P-MDCT-CA) in comparison with retrospective ECG-gated MDCT-CA (R-MDCT-CA). The influence of kilovoltage and body mass index on radiation dose and the impact of different parameters on image quality (IQ) and diagnostic confidence (DC), were also determined. METHODS: 64-slice MDCT-CA was performed in 176 patients: 66 R-MDCT-CA and 110 P-MDCT-CA. Effective dose was determined using ImpactDose software based on Monte Carlo method. Three point scales were used to assess IQ and DC on a segmental basis. RESULTS: Patients were divided into 4 groups according with the examination performed: group A (90 pts, coronary tree assessment with P-MDCT-CA); group B (55 pts, coronary tree assessment with R-MDCT-CA); group C (20 pts, bypass grafts assessment with P-MDCT-CA); and group D (11 pts, bypass grafts assessment with R-MDCT-CA). Effective dose was 68% lower for P-MDCT-CA than R-MDCT-CA for coronary artery studies (Gr. A=4.7 ± 1.69 mSv and Gr. B=14.9 ± 4.4 mSv; p<0.05) and 63% lower for by-pass studies. Effective dose resulted significantly higher in women than in men who underwent R-MDCT-CA; conversely, no gender impact was observed on effective dose of P-MDCT-CA. As a result, dose saving with prospective gating was more pronounced in women (73%; R-MDCT-CA:16.3 mSv, P-MDCT-CA:4.5 mSv,) than in men (60%; R-MDCT-CA:12.8 mSv, P-MDCT-CA:4.8 mSv). IQ and DC of P-MDCT-CA were better or comparable than R-MDCT-CA CONCLUSIONS: P-MDCT-CA provides at least comparable IQ and DC than R-MDCT-CA with significant dose saving. This study highlights the important advantage offered by using P-MDCT-CA in female patients.

Totally synthetic peptide-based immunocontraceptive vaccines show activity in dogs of different breeds.

In this study we examine the immunogenicity of totally synthetic peptide-based immunocontraceptive vaccines in dogs. Seven individual epitope-based vaccines were assembled in which a different T helper (T(H)) cell epitope derived from the sequence of F protein of canine distemper virus was synthesized in tandem with a peptide representing luteinising hormone releasing hormone (LHRH). Each of the individual T(H)-LHRH peptide vaccines was inoculated subcutaneously into dogs. The results demonstrate that five of the seven peptide vaccines were able to elicit strong anti-LHRH antibody responses in beagle foxhounds accompanied by a concomitant suppression in the levels of the hormones testosterone and progesterone in the majority of the animals. A pool of these five peptides was then used to inoculate five different breeds of dogs. All animals responded with high levels of anti-LHRH antibody. An investigation of the proliferative responses of peripheral blood mononuclear cells (PBMC) obtained from inoculated dogs showed that the majority of breeds responded to each of the individual T helper cell epitope tested. The results provide a strategy for development of an immunocontraceptive vaccine for use in multiple breeds of dogs.