Anatomical characteristics and dimensions of edentulous sites in the posterior maxillae of patients referred for implant therapy

The purpose of this study was to analyze the width and height of edentulous sites in the posterior maxilla using cone beam computed tomography (CBCT) images from patients referred for implant therapy. A total of 122 CBCT scans were included in the analysis, resulting in a sample size of 252 edentulous sites. The orofacial crest width was measured in coronal slices, perpendicular to the alveolar ridge. The bone height was analyzed in the respective sagittal slices. Additionally, the following secondary outcome parameters were evaluated: the morphology of the sinus floor, the presence of septa in the maxillary sinus, and the thickness of the sinus membrane. The mean crest width for all analyzed sites was 8.28 mm, and the mean bone height was 7.22 mm. The percentage of patients with a crest width of less than 6 mm was 27% in premolar sites and 7.8% in molar sites. The bone height decreased from premolar to molar areas, with a high percentage of first and second molar sites exhibiting a bone height of less than 5 mm (54.12% and 44.64%, respectively). Regarding the morphology of the sinus floor, 53% of the edentulous sites exhibited a flat configuration. A septum was present in 67 edentulous sites (26.59%). Analysis of the sinus membrane revealed 88 sites (34.9%) with increased mucosal thickness (> 2 mm). For the crest width, the location of the edentulous site and the morphology of the sinus floor were both statistically significant variables. For the crest width and mean bone height, the location of the edentulous site and the morphology of the sinus floor were both statistically significant variables. The study confirmed that a high percentage of edentulous sites in the posterior maxilla do require sinus floor elevation to allow the placement of dental implants. Therefore, a detailed three-dimensional radiograph using CBCT is indicated in most patients for proper treatment planning.

Dimensions of the Ascending Aorta in Conotruncal Heart Defects

Dilatation of the ascending aorta is an important sequel in conotruncal anomalies, such as tetralogy of Fallot (TOF) or d-transposition of the great arteries (TGA). We measured dimensions and their progression at different levels of the ascending aorta in 80 patients. In TOF patients, mean z-score for aortic annulus was 1.65 (range -3.16-6.47), for sinus 1.93 (range -2.28-5.39), for st-junction 4.15 (range 0.0-8.18), and for ascending aorta 3.51 (range -1.23-6.36). Over time, annulus z-scores increased in the univariate analysis [0.07/year, 95 % confidence interval (CI) 0.01-0.14; p = 0.02], and this was unique to male patients (0.08/year, 95 % CI 0.00-0.15; p = 0.05). z-scores of the ascending aorta decreased (-0.1/year, 95 % CI -0.18 to -0.02; p = 0.02), and this was confined to patients without aortic regurgitation (AR; -0.09/year, 95 % CI -0.18 to -0.01; p = 0.04). In TGA, mean z-score for the aortic annulus was 2.13 (range -3.71-8.39), for sinus 1.77 (range -3.04-6.69), for st-junction 1.01 (range -5.44-6.71), and for ascending aorta 0.82 (range -4.91-6.46). In bivariate analysis, annulus z-scores decreased in females (-0.14/year, 95 % CI -0.25 to -0.03; p = 0.01) and in patients without AR (-0.07/year, 95 % CI -0.14-0.0; p = 0.03). z-scores of the ascending aorta increased significantly in males (0.08/year, 95 % CI 0.0 to 0.16; p = 0.05) and in patients with AR (0.12/year, 95 % CI 0.03-0.21; p = 0.01). In conclusion, TOF and TGA z-scores of the ascending aorta differ significantly from those of the normal population. Progression of z-scores over time is influenced by diagnosis, sex, and presence of AR.

Electrophysiologic characterization of local abnormal ventricular activities in postinfarction ventricular tachycardia with respect to their anatomic location.

BACKGROUND Local abnormal ventricular activities (LAVA) in patients with scar-related ventricular tachycardia (VT) may appear at any time during or after the far-field electrogram. Although they may be separated from the far-field signal by an isoelectric line and extend beyond the end of surface QRS, they may also appear fused or buried within the QRS. OBJECTIVE The purpose of this study was to characterize LAVA in postinfarction VT patients with respect to their anatomic locations. METHODS Thirty-one patients with postinfarction VT underwent mapping/ablation during sinus rhythm with a three-dimensional electroanatomic mapping system. From a total of 18,270 electrograms reviewed in all study subjects, 1104 LAVA (endocardium 839, epicardium 265) were identified and analyzed. RESULTS The interval from onset of QRS complex to ventricular electrogram (EGM onset) on the endocardium was significantly shorter than the epicardium (P < .001). EGM onset was shortest in the septal endocardium and longest in the inferior and lateral epicardium. There was a significant positive correlation between EGM onset and LAVA lateness as estimated by the interval from surface QRS onset to LAVA (r = 0.52, P < .001). LAVA were more frequently detected after the QRS complex in the epicardium (241/265 [91%]) than in the endocardium (551/839 [66%], P < .001). Only 43% of endocardial septal LAVA were detected after the QRS complex. CONCLUSION Lateness of LAVA is affected to a large extent by their locations. The chance of detecting late LAVA increases when electrogram onset is later. Substrate-based approach targeting delayed signals relative to the QRS complex may miss critical the arrhythmogenic substrate, particularly in the septum and other early-to-activate regions.

Endocardial versus epicardial ventricular radiofrequency ablation: utility of in vivo contact force assessment.

BACKGROUND Contact force (CF) is an important determinant of lesion formation for atrial endocardial radiofrequency ablation. There are minimal published data on CF and ventricular lesion formation. We studied the impact of CF on lesion formation using an ovine model both endocardially and epicardially. METHODS AND RESULTS Twenty sheep received 160 epicardial and 160 endocardial ventricular radiofrequency applications using either a 3.5-mm irrigated-tip catheter (Thermocool, Biosense-Webster, n=160) or a 3.5 irrigated-tip catheter with CF assessment (Tacticath, Endosense, n=160), via percutaneous access. Power was delivered at 30 watts for 60 seconds, when either catheter/tissue contact was felt to be good or when CF>10 g with Tacticath. After completion of all lesions, acute dimensions were taken at pathology. Identifiable lesion formation from radiofrequency application was improved with the aid of CF information, from 78% to 98% on the endocardium (P<0.001) and from 90% to 100% on the epicardium (P=0.02). The mean total force was greater on the endocardium (39±18 g versus 21±14 g for the epicardium; P<0.001) mainly because of axial force. Despite the force-time integral being greater endocardially, epicardial lesions were larger (231±182 mm(3) versus 209±131 mm(3); P=0.02) probably because of the absence of the heat sink effect of the circulating blood and covered a greater area (41±27 mm(2) versus 29±17 mm(2); P=0.03) because of catheter orientation. CONCLUSIONS In the absence of CF feedback, 22% of endocardial radiofrequency applications that are thought to have good contact did not result in lesion formation. Epicardial ablation is associated with larger lesions.

Integration of merged delayed-enhanced magnetic resonance imaging and multidetector computed tomography for the guidance of ventricular tachycardia ablation: a pilot study

BACKGROUND Delayed enhancement (DE) MRI can assess the fibrotic substrate of scar-related VT. MDCT has the advantage of inframillimetric spatial resolution and better 3D reconstructions. We sought to evaluate the feasibility and usefulness of integrating merged MDCT/MRI data in 3D-mapping systems for structure-function assessment and multimodal guidance of VT mapping and ablation. METHODS Nine patients, including 3 ischemic cardiomyopathy (ICM), 3 nonischemic cardiomyopathy (NICM), 2 myocarditis, and 1 redo procedure for idiopathic VT, underwent MRI and MDCT before VT ablation. Merged MRI/MDCT data were integrated in 3D-mapping systems and registered to high-density endocardial and epicardial maps. Low-voltage areas (<1.5 mV) and local abnormal ventricular activities (LAVA) during sinus rhythm were correlated to DE at MRI, and wall-thinning (WT) at MDCT. RESULTS Endocardium and epicardium were mapped with 391 ± 388 and 1098 ± 734 points per map, respectively. Registration of MDCT allowed visualization of coronary arteries during epicardial mapping/ablation. In the idiopathic patient, integration of MRI data identified previously ablated regions. In ICM patients, both DE at MRI and WT at MDCT matched areas of low voltage (overlap 94 ± 6% and 79 ± 5%, respectively). In NICM patients, wall-thinning areas matched areas of low voltage (overlap 63 ± 21%). In patients with myocarditis, subepicardial DE matched areas of epicardial low voltage (overlap 92 ± 12%). A total number of 266 LAVA sites were found in 7/9 patients. All LAVA sites were associated to structural substrate at imaging (90% inside, 100% within 18 mm). CONCLUSION The integration of merged MDCT and DEMRI data is feasible and allows combining substrate assessment with high-spatial resolution to better define structure-function relationship in scar-related VT.

What next after failed septal ventricular tachycardia ablation?

Ablation of ventricular tachycardia (VT) by conventional radiofrequency ablation can be impossible if the ventricular wall at the targeted ablation site is very thick, as for example the ventricular septum. We present a case of a patient with incessant, non-sustained slow VT originating from the septal part of the lower outflow tracts. Radiofrequency catheter ablation from both ventricles as well as from the anterior cardiac vein were not successful. Both high power radiofrequency ablation and bipolar radiofrequency ablation neither were successfull. Finally, ethanol ablation of the first septal perforator successfully terminated arrhythmia. We discuss the possibilities to overcome failed conventional radiofrequency VT ablation of a septal focus.

Noninvasive electrocardiographic mapping for prediction of tachycardia mechanism and origin of atrial tachycardia following bilateral pulmonary transplantation

This is a case of atrial tachycardia 2 years after pulmonary transplantation. After excluding right atrial involvement, tachycardia origin was located in a scar region medial to the anastomosis of the left inferior pulmonary donor vein. Tachycardia mechanism was microreentry. Noninvasive electrocardiographic mapping performed before the ablation procedure matched with results of invasive Carto mapping and predicted both tachycardia mechanism and origin. We discuss arrhythmia mechanism found after pulmonary transplantation and benefit of noninvasive electrocardiographic mapping for procedure planning.

Pathogenesis of AF: impact on intracardiac signals

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and is responsible for the highest number of rhythm-related disorders and cardioembolic strokes worldwide. Intracardiac signal analysis during the onset of paroxysmal AF led to the discovery of pulmonary vein as a triggering source of AF, which has led to the development of pulmonary vein ablation--an established curative therapy for drug-resistant AF. Complex, multicomponent and rapid electrical activity widely involving the atrial substrate characterizes persistent/permanent AF. Widespread nature of the problem and complexity of signals in persistent AF reduce the success rate of ablation therapy. Although signal processing applied to extraction of relevant features from these complex electrograms has helped to improve the efficacy of ablation therapy in persistent/permanent AF, improved understanding of complex signals should help to identify sources of AF and further increase the success rate of ablation therapy.

Spectrum and prevalence of mutations involving BrS1- through BrS12-susceptibility genes in a cohort of unrelated patients referred for Brugada syndrome genetic testing: implications for genetic testing

OBJECTIVES The aim of this study was to provide the spectrum and prevalence of mutations in the 12 Brugada syndrome (BrS)-susceptibility genes discovered to date in a single large cohort of unrelated BrS patients. BACKGROUND BrS is a potentially lethal heritable arrhythmia syndrome diagnosed electrocardiographically by coved-type ST-segment elevation in the right precordial leads (V1 to V3; type 1 Brugada electrocardiographic [ECG] pattern) and the presence of a personal/family history of cardiac events. METHODS Using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing, comprehensive mutational analysis of BrS1- through BrS12-susceptibility genes was performed in 129 unrelated patients with possible/probable BrS (46 with clinically diagnosed BrS [ECG pattern plus personal/family history of a cardiac event] and 83 with a type 1 BrS ECG pattern only). RESULTS Overall, 27 patients (21%) had a putative pathogenic mutation, absent in 1,400 Caucasian reference alleles, including 21 patients with an SCN5A mutation, 2 with a CACNB2B mutation, and 1 each with a KCNJ8 mutation, a KCND3 mutation, an SCN1Bb mutation, and an HCN4 mutation. The overall mutation yield was 23% in the type 1 BrS ECG pattern-only patients versus 17% in the clinically diagnosed BrS patients and was significantly greater among young men<20 years of age with clinically diagnosed BrS and among patients who had a prolonged PQ interval. CONCLUSIONS We identified putative pathogenic mutations in ∼20% of our BrS cohort, with BrS genes 2 through 12 accounting for <5%. Importantly, the yield was similar between patients with only a type 1 BrS ECG pattern and those with clinically established BrS. The yield approaches 40% for SCN5A-mediated BrS (BrS1) when the PQ interval exceeds 200 ms. Calcium channel-mediated BrS is extremely unlikely in the absence of a short QT interval.

A novel rare variant in SCN1Bb linked to Brugada syndrome and SIDS by combined modulation of Na(v)1.5 and K(v)4.3 channel currents.

BACKGROUND Cardiac sodium channel β-subunit mutations have been associated with several inherited cardiac arrhythmia syndromes. OBJECTIVE To identify and characterize variations in SCN1Bb associated with Brugada syndrome (BrS) and sudden infant death syndrome (SIDS). METHODS All known exons and intron borders of the BrS-susceptibility genes were amplified and sequenced in both directions. Wild type (WT) and mutant genes were expressed in TSA201 cells and studied using co-immunoprecipitation and whole-cell patch-clamp techniques. RESULTS Patient 1 was a 44-year-old man with an ajmaline-induced type 1 ST-segment elevation in V1 and V2 supporting the diagnosis of BrS. Patient 2 was a 62-year-old woman displaying a coved-type BrS electrocardiogram who developed cardiac arrest during fever. Patient 3 was a 4-month-old female SIDS case. A R214Q variant was detected in exon 3A of SCN1Bb (Na(v)1B) in all three probands, but not in any other gene previously associated with BrS or SIDS. R214Q was identified in 4 of 807 ethnically-matched healthy controls (0.50%). Co-expression of SCN5A/WT + SCN1Bb/R214Q resulted in peak sodium channel current (I(Na)) 56.5% smaller compared to SCN5A/WT + SCN1Bb/WT (n = 11-12, P<0.05). Co-expression of KCND3/WT + SCN1Bb/R214Q induced a Kv4.3 current (transient outward potassium current, I(to)) 70.6% greater compared with KCND3/WT + SCN1Bb/WT (n = 10-11, P<0.01). Co-immunoprecipitation indicated structural association between Na(v)β1B and Na(v)1.5 and K(v)4.3. CONCLUSION Our results suggest that R214Q variation in SCN1Bb is a functional polymorphism that may serve as a modifier of the substrate responsible for BrS or SIDS phenotypes via a combined loss of function of sodium channel current and gain of function of transient outward potassium current.

LQTS-associated mutation A257G in α1-syntrophin interacts with the intragenic variant P74L to modify its biophysical phenotype.

The SNTA1-encoded α1-syntrophin (SNTA1) missense mutation, p.A257G, causes long QT syndrome (LQTS) by pathogenic accentuation of Nav1.5's sodium current (I Na). Subsequently, we found p.A257G in combination with the SNTA1 polymorphism, p.P74L in 4 victims of sudden infant death syndrome (SIDS) as well as in 3 adult controls. We hypothesized that p.P74L-SNTA1 could functionally modify the pathogenic phenotype of p.A257G-SNTA1, thus explaining its occurrence in non-LQTS populations. The SNTA1 variants p.P74L, p.A257G, and the combination variant p.P74L/p.A257G were engineered using PCR-based overlap-extension and were co-expressed heterologously with SCN5A in HEK293 cells. I Na was recorded using the whole-cell method. Compared to wild-type (WT), the significant increase in peak I Na and window current found with p.A257G was reversed by the intragenic variant p.P74L (p.P74L/p.A257G). These results report for the first time the intragenic rescue of an LQT-associated SNTA1 mutation when found in combination with the SNTA1 polymorphism p.P74L, suggesting an ever-increasing picture of complexity in terms of genetic risk stratification for arrhythmia.

Alpha1-syntrophin mutations identified in sudden infant death syndrome cause an increase in late cardiac sodium current.

BACKGROUND Sudden infant death syndrome (SIDS) is a leading cause of death during the first 6 months after birth. About 5% to 10% of SIDS may stem from cardiac channelopathies such as long-QT syndrome. We recently implicated mutations in alpha1-syntrophin (SNTA1) as a novel cause of long-QT syndrome, whereby mutant SNTA1 released inhibition of associated neuronal nitric oxide synthase by the plasma membrane Ca-ATPase PMCA4b, causing increased peak and late sodium current (I(Na)) via S-nitrosylation of the cardiac sodium channel. This study determined the prevalence and functional properties of SIDS-associated SNTA1 mutations. METHODS AND RESULTS Using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing of SNTA1's open reading frame, 6 rare (absent in 800 reference alleles) missense mutations (G54R, P56S, T262P, S287R, T372M, and G460S) were identified in 8 (approximately 3%) of 292 SIDS cases. These mutations were engineered using polymerase chain reaction-based overlap extension and were coexpressed heterologously with SCN5A, neuronal nitric oxide synthase, and PMCA4b in HEK293 cells. I(Na) was recorded using the whole-cell method. A significant 1.4- to 1.5-fold increase in peak I(Na) and 2.3- to 2.7-fold increase in late I(Na) compared with controls was evident for S287R-, T372M-, and G460S-SNTA1 and was reversed by a neuronal nitric oxide synthase inhibitor. These 3 mutations also caused a significant depolarizing shift in channel inactivation, thereby increasing the overlap of the activation and inactivation curves to increase window current. CONCLUSIONS Abnormal biophysical phenotypes implicate mutations in SNTA1 as a novel pathogenic mechanism for the subset of channelopathic SIDS. Functional studies are essential to distinguish pathogenic perturbations in channel interacting proteins such as alpha1-syntrophin from similarly rare but innocuous ones.

Unique mixed phenotype and unexpected functional effect revealed by novel compound heterozygosity mutations involving SCN5A.

BACKGROUND Functional characterization of mutations involving the SCN5A-encoded cardiac sodium channel has established the pathogenic mechanisms for type 3 long QT syndrome and type 1 Brugada syndrome and has provided key insights into the physiological importance of essential structure-function domains. OBJECTIVE This study sought to present the clinical and biophysical phenotypes discerned from compound heterozygosity mutations in SCN5A on different alleles in a toddler diagnosed with QT prolongation and fever-induced ventricular arrhythmias. METHODS A 22-month-old boy presented emergently with fever and refractory ventricular tachycardia. Despite restoration of sinus rhythm, the infant sustained profound neurological injury and died. Using polymerase chain reaction, denaturing high-performance liquid chromatography, and direct DNA sequencing, comprehensive open-reading frame/splice mutational analysis of the 12 known long QT syndrome susceptibility genes was performed. RESULTS The infant had 2 SCN5A mutations: a maternally inherited N-terminal frame shift/deletion (R34fs/60) and a paternally inherited missense mutation, R1195H. The mutations were engineered by site-directed mutagenesis and heterologously expressed transiently in HEK293 cells. As expected, the frame-shifted and prematurely truncated peptide, SCN5A-R34fs/60, showed no current. SCN5A-R1195H had normal peak and late current but abnormal voltage-dependent gating parameters. Surprisingly, co-expression of SCN5A-R34fs/60 with SCN5A-R1195H elicited a significant increase in late sodium current, whereas co-expression of SCN5A-WT with SCN5A-R34fs/60 did not. CONCLUSIONS A severe clinical phenotype characterized by fever-induced monomorphic ventricular tachycardia and QT interval prolongation emerged in a toddler with compound heterozygosity involving SCN5A: R34fs/60, and R1195H. Unexpectedly, the 94-amino-acid fusion peptide derived from the R34fs/60 mutation accentuated the late sodium current of R1195H-containing Na(V)1.5 channels in vitro.

SCN4B-encoded sodium channel beta4 subunit in congenital long-QT syndrome.

BACKGROUND Congenital long-QT syndrome (LQTS) is potentially lethal secondary to malignant ventricular arrhythmias and is caused predominantly by mutations in genes that encode cardiac ion channels. Nearly 25% of patients remain without a genetic diagnosis, and genes that encode cardiac channel regulatory proteins represent attractive candidates. Voltage-gated sodium channels have a pore-forming alpha-subunit associated with 1 or more auxiliary beta-subunits. Four different beta-subunits have been described. All are detectable in cardiac tissue, but none have yet been linked to any heritable arrhythmia syndrome. METHODS AND RESULTS We present a case of a 21-month-old Mexican-mestizo female with intermittent 2:1 atrioventricular block and a corrected QT interval of 712 ms. Comprehensive open reading frame/splice mutational analysis of the 9 established LQTS-susceptibility genes proved negative, and complete mutational analysis of the 4 Na(vbeta)-subunits revealed a L179F (C535T) missense mutation in SCN4B that cosegregated properly throughout a 3-generation pedigree and was absent in 800 reference alleles. After this discovery, SCN4B was analyzed in 262 genotype-negative LQTS patients (96% white), but no further mutations were found. L179F was engineered by site-directed mutagenesis and heterologously expressed in HEK293 cells that contained the stably expressed SCN5A-encoded sodium channel alpha-subunit (hNa(V)1.5). Compared with the wild-type, L179F-beta4 caused an 8-fold (compared with SCN5A alone) and 3-fold (compared with SCN5A + WT-beta4) increase in late sodium current consistent with the molecular/electrophysiological phenotype previously shown for LQTS-associated mutations. CONCLUSIONS We provide the seminal report of SCN4B-encoded Na(vbeta)4 as a novel LQT3-susceptibility gene.

Follow-up of a group of patients with automatic implantable defibrillator

UNLABELLED The automatic implantable defibrillator (AID) is the treatment of choice for primary and secondary prevention of sudden death. At the Instituto Nacional de Cardiología, since October 1996 until January 2002, 25 patients were implanted with 26 AID. There were 23 men (92%) and the mean age of the whole group, was 51.4 years. Twenty-three patients (92%) presented structural heart disease, the most common was ischemic heart disease in 13 patients (52%), with a mean ejection fraction of 37.8%. One patient without structural heart disease had Brugada Syndrome. The most frequent clinical arrhythmia was ventricular tachycardia in 14 patients (56%). The mean follow-up was of 29.3 months during which a total of 30 events of ventricular arrhythmia were treated through AID; six of them were inappropriate due to paroxismal atrial fibrillation; 10 AID patients (34%) have not applied for therapy. Three patients (12%) of the group died due to congestive heart failure refractory to pharmacologic treatment. CONCLUSION The implant of the AID is a safe and effective measure for primary and secondary prevention of sudden death. World-wide experience evidences, that this kind of device has not modified the mortality rate due to heart failure in these patients, but it has diminished sudden arrhythmic death.