Ventricular tachycardia arising from the aortomitral continuity in structural heart disease: characteristics and therapeutic considerations for an anatomically challenging area of origin

BACKGROUND: The aortomitral continuity (AMC) has been described as a site of origin for ventricular tachycardias (VT) in structurally normal hearts. There is a paucity of data on the contribution of this region to VTs in patients with structural heart disease. METHODS AND RESULTS: Data from 550 consecutive patients undergoing catheter ablation for VT associated with structural heart disease were reviewed. Twenty-one (3.8%) had a VT involving the peri-AMC region (age, 62.7+/-11 years; median left ventricular ejection fraction, 43.6+/-17%). Structural heart disease was ischemic in 7 (33%), dilated cardiomyopathy in 10 (47.6%), and valvular cardiomyopathy in 4 (19%) patients, respectively. After 1.9+/-0.8 catheter ablation procedures (including 3 transcoronary ethanol ablations) the peri-AMC VT was not inducible in 19 patients. The remaining 2 patients underwent cryosurgical ablation. Our first catheter ablation procedure was less often successful (66.7%) for peri-AMC VTs compared with that for 246 VTs originating from the LV free wall (81.4%, P=0.03). During a mean follow-up of 1.9+/-2.1 years, 12 (57.1%) patients remained free of VT, peri-AMC VT recurred in 7 patients, and 1 patient had recurrent VT from a remote location. Three patients died. Analysis of 50 normal coronary angiograms demonstrated an early septal branch supplying the peri-AMC area in 58% of cases that is a potential target for ethanol ablation. CONCLUSIONS: VTs involving the peri-AMC region occur in patients with structural heart disease and appear to be more difficult to ablate compared with VTs originating from the free LV wall. This region provides unique challenges for radiofrequency ablation, but cryosurgery and transcoronary alcohol ablation appear feasible in some cases.

Low prevalence of atrial fibrillation in asymptomatic adults in Geneva, Switzerland

Aims To determine the prevalence of atrial fibrillation (AF) in a population-based sample of adults. Methods and results Between January 2005 and December 2007 individuals aged >/=50 years, residents of the city of Geneva, who had participated in a previous random survey were invited for follow-up examination. AF was assessed on a single resting 6-lead ECG. Reported prevalences were standardized for the age distribution of Canton Geneva. Overall participation was 72.8%. Twenty-nine cases of AF (22 men) were diagnosed among 3285 subjects (1696 men). The crude prevalence of AF (95% CI) was 0.88% (0.86, 0.90) overall, but higher in men [1.30% (1.26, 1.34)] than in women [0.44% (0.41, 0.47)]. The age-standardized AF prevalence was slightly higher [overall: 0.94% (0.91, 0.97), men: 1.23% (1.19, 1.27), women: 0.54% (0.47, 0.61)]. AF prevalence increased with age in both sexes. A 'history of suspected arterial embolism' (brain or legs) was higher in the AF cases (10.3 vs. 3.3%; P = 0.03). Conclusion This population-based survey of a general Swiss population indicates that the prevalence of AF remains below 1%. These results are less alarming than those from previous studies based on patients seeking medical care.

Transalveolar maxillary sinus floor elevation using osteotomes with or without grafting material. Part II: Radiographic tissue remodeling

OBJECTIVES: To evaluate the pattern of tissue remodeling after maxillary sinus floor elevation using the transalveolar osteotome technique with or without utilizing grafting materials. METHODS: During the period of 2000-2005, 252 Straumann dental implants were inserted using the transalveolar sinus floor elevation technique in a group of 181 patients. For 88 or 35% of those implants, deproteinized bovine bone mineral with a particle size of 0.25-1 mm was used as the grafting material, but for the remaining 164 implants, no grafting material was utilized. Periapical radiographs were obtained with a paralleling technique and digitized. Two investigators, who were blinded to whether grafting material was used or not, subsequently evaluated the pattern of tissue remodeling. RESULTS: The mean residual bone height was 7.5 mm (SD 2.2 mm), ranging from 2 to 12.7 mm. The mean residual bone height for implants placed with grafting material (6.4 mm) was significantly less compared with the implants installed without grafting material (8.1 mm). The implants penetrated on average 3.1 mm (SD 1.7 mm) into the sinus cavity. The measured mean radiographic bone gain using the transalveolar technique without grafting material was significantly less, 1.7 mm (SD 2 mm) compared with a mean bone gain of 4.1 mm (SD 2.4 mm), when grafting material was used. Furthermore, the probability of gaining 2 mm or more of new bone was 39.1% when no grafting material was used. The probability increased to 77.9% when the implants were installed with grafting material. CONCLUSION: When the transalveolar sinus floor elevation was performed without utilizing grafting material, only a moderate gain of new bone could be detected mesial and distal to the implants. On the other hand, when grafting material was used, a substantial gain of new bone was usually seen on the radiographs.

Ventricular tachycardia in a Brugada syndrome patient caused by a novel deletion in SCN5A

The aim of the present study was to identify the molecular mechanism behind ventricular tachycardia in a patient with Brugada syndrome. Arrhythmias in patients with Brugada syndrome often occur during sleep. However, a 28-year-old man with no previously documented arrhythmia or syncope who experienced shortness of breath and chest pain during agitation is described. An electrocardiogram revealed monomorphic ventricular tachycardia; after he was converted to nodal rhythm, he spontaneously went into sinus rhythm, and showed classic Brugada changes with coved ST elevation in leads V(1) to V(2). Mutation analysis of SCN5A revealed a novel mutation, 3480 deletion T frame shift mutation, resulting in premature truncation of the protein. Heterologous expression of this truncated protein in human embryonic kidney 293 cells showed a markedly reduced protein expression level. By performing whole-cell patch clamp experiments using human embryonic kidney 293 cells transfected with the mutated SCN5A, no current could be recorded. Hence, the results suggest that the patient suffered from haploinsufficiency of Na(v)1.5, and that this mutation was the cause of his Brugada syndrome.

Contractile function is preserved in unloaded hearts despite atrophic remodeling

OBJECTIVE: Recent studies have shown that mechanically unloading a failing heart may induce reverse remodeling and functional improvement. However, these benefits may be balanced by an unloading-related remodeling including myocardial atrophy that might lead to decrease in function. Using a model of heterotopic heart transplantation, we aimed to characterize the myocardial changes induced by long-term unloading. MATERIAL AND METHODS: Macroscopic as well as cellular and functional changes were followed in normal hearts unloaded for a 3-month period. Microscopic parameters were evaluated with stereologic methodology. Myocardial contractile function was quantified with a Langendorff isolated, perfused heart technique. RESULTS: Atrophy was macroscopically obvious and accompanied by a 67% reduction of the myocyte volume and a 43% reduction of the interstitial tissue volume, thus accounting for a shift of the myocyte/connective tissue ratio in favor of noncontractile tissue. The absolute number of cardiomyocyte nuclei decreased from 64.7 +/- 5.1 x 10(7) in controls to 22.6 +/- 3.7 x 10(7) (30 days) and 21.6 +/- 3.1 x 10(7) (90 days) after unloading (P < .05). The numeric nucleic density in the unloaded myocardium, as well as the mean cardiomyocyte volume per cardiomyocyte nucleus, remained constant throughout the 90 days of observation. Functional data indicated an increase in ventricular stiffness, although contractile function was preserved, as confirmed by unaltered maximal developed pressure and increased contractility (maximum rate of left ventricular pressure development) and relaxation (minimum rate of left ventricular pressure development). CONCLUSION: Atrophic remodeling involves both the myocyte and interstitial tissue compartment. These data suggest that although there is decreased myocardial volume and increased stiffness, contractile capacity is preserved in the long-term unloaded heart.

PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature

The transmembrane ligand ephrinB2 and its cognate Eph receptor tyrosine kinases are important regulators of embryonic blood vascular morphogenesis. However, the molecular mechanisms required for ephrinB2 transduced cellular signaling in vivo have not been characterized. To address this question, we generated two sets of knock-in mice: ephrinB2DeltaV mice expressed ephrinB2 lacking the C-terminal PDZ interaction site, and ephrinB2(5F) mice expressed ephrinB2 in which the five conserved tyrosine residues were replaced by phenylalanine to disrupt phosphotyrosine-dependent signaling events. Our analysis revealed that the homozygous mutant mice survived the requirement of ephrinB2 in embryonic blood vascular remodeling. However, ephrinB2DeltaV/DeltaV mice exhibited major lymphatic defects, including a failure to remodel their primary lymphatic capillary plexus into a hierarchical vessel network, hyperplasia, and lack of luminal valve formation. Unexpectedly, ephrinB2(5F/5F) mice displayed only a mild lymphatic phenotype. Our studies define ephrinB2 as an essential regulator of lymphatic development and indicate that interactions with PDZ domain effectors are required to mediate its functions.

Myc regulates embryonic vascular permeability and remodeling

Previous work has shown that c-Myc is required for adequate vasculogenesis and angiogenesis. To further investigate the contribution of Myc to these processes, we conditionally expressed c-Myc in embryonic endothelial cells using a tetracycline-regulated system. Endothelial Myc overexpression resulted in severe defects in the embryonic vascular system. Myc-expressing embryos undergo widespread edema formation and multiple hemorrhagic lesions. They die between embryonic days 14.5 and 17.5. The changes in vascular permeability are not caused by deficiencies in vascular basement membrane composition or pericyte coverage. However, the overall turnover of endothelial cells is elevated as is revealed by increased levels of both proliferation and apoptosis. Whole-mount immunohistochemical analysis revealed alterations in the architecture of capillary networks. The dermal vasculature of Myc-expressing embryos is characterized by a reduction in vessel branching, which occurs despite upregulation of the proangiogenic factors vascular endothelial growth factor-A and angiopoietin-2. Thus, the net outcome of an excess of vascular endothelial growth factor-A and angiopoietin-2 in the face of an elevated cellular turnover appears to be a defect in vascular integrity.

Cardiopulmonary bypass reduces atrial Na+-K+-ATPase expression in children

Cardiopulmonary bypass (CPB) may induce serious side effects, potentially leading to myocardial failure. The Na(+)-K(+)-ATPase is a key component for myocardial function. Due to its developmental regulation, results from adult studies cannot be adopted to the situation in childhood. Right atrial myocardium from patients with left-to-right shunts at atrial level (VO, n=8) and those without (NO, n=8) was excised during heart surgery before and after CPB. Na(+)-K(+)-ATPase isoforms ATP1A1 (p=0.008) and ATP1A3 (p=0.038) decreased during CPB, which decrease was restricted to the VO group. This study highlights the importance of the underlying heart defect for susceptibility to the effects of CPB, showing a reduced Na(+)-K(+)-ATPase mRNA expression only in patients with left-to-right shunts on the atrial level. This seemed to be an early molecular event, as apart from one, none of the patients showed heart failure before or after surgery.

Age-dependent suppression of SERCA2a mRNA in pediatric atrial myocardium

Differential expression of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) and phospholamban (PLB) has been shown in heart failure and atrial arrhythmias. We investigated the influence of volume overload and age on their expression in pediatric atrial myocardium. Right atrial specimens from 18 children with volume overloaded right atrium (VO) and 12 patients without overload were studied. Each group was further divided into patients less than and older than 12 months of age. Only in the younger patients SERCA2a was significantly reduced in the VO group. In younger patients PLB mRNA level tended to be lower in VO. The PLB:SERCA protein ratio was significantly reduced in the VO group. Age itself did not influence the SERCA2a and PLB expression, if the hemodynamic overload was not taken into account. This study is the first to show a combined influence of volume overload and age on atrial SERCA2a expression.