Gender differences in accessory connections location: an Israeli study
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- Birati, E.Y., Eldar, M. & Belhassen, B. J Interv Card Electrophysiol (2012) 34: 227. doi:10.1007/s10840-012-9683-4
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Recent studies have shown that the pathogenesis of accessory connections (AC) formation may have a genetic component.
The purpose of the study was to examine whether AC location differs by gender in a large cohort of patients with AC undergoing radiofrequency ablation (RFA) in two Israeli electrophysiology (EP) laboratories.
All consecutive patients who underwent RFA of single ACs in Tel Aviv Sourasky Medical Center between 1992 and 2009 (n = 574) as well as the first consecutive 230 patients who underwent RFA in Sheba Medical Center between 1992 and 2001 were included in this study.
The 804 patients in the two centers included 511 males (63.6 %) and 293 (36.4 %) females, mean age 34 + 16 years old. The AC was located in the left free wall, posteroseptal, right free wall, right anteroseptal, and in other areas in 57.8, 22.8, 9.3, 7 and 3.1 % of patients, respectively. The anatomical AC distribution was similar in the two EP laboratories. A right free wall location was more frequent in females (13 %) than in males (7.2 %; p = 0.008). A right anteroseptal location was more frequent in males (8.4 %) than in females (4.4 %) (p = 0.043). The left free wall and posteroseptal locations were similarly encountered in males (58.1 and 23.1 %, respectively) and in females (57.3 and 22.2 %, respectively).
In our Israeli population, females more commonly have right free wall ACs and males more commonly have right anteroseptal ACs. These findings support the possible role of a genetic component in the pathogenesis of AC formation.
The Wolff–Parkinson–White (WPW) syndrome is the second most common cause of paroxysmal supraventricular tachycardia in most parts of the world, with prevalence of 1.5 to 3.1 per 1,000 persons in western countries . This syndrome is thought to be secondary to accessory connections (AC) formation during cardiogenesis that provide direct continuity between atrial and ventricular myocardium [1, 2]. By definition, WPW syndrome requires evidence of pre-excitation in the ECG. Some patients suffer from “concealed ACs”, which conduct only retrogradely and thus do not affect the baseline ECG.
The genetic role of this syndrome is unknown, with few anecdotal reports published to date, showing various modes of inheritance. In the majority of cases, WPW syndrome has no clear familial involvement, but a minority of cases results from an inherited disease or occurs as part of a syndrome with a strong genetic basis . In one report, Gollob et al.  studied 70 members of two families in which the WPW syndrome segregated as an autosomal dominant disorder . Hsu et al.  described the variability of different AC locations by gender in American patients. They found a female predominance of right annular AC and concluded that the pathogenesis of AC formation may have a genetic component.
The aim of the present study was to assess the possibility of genetic component in Israeli patients with ACs (both manifest and concealed) who underwent radiofrequency ablation (RFA) in two cardiac electrophysiology laboratories.
All consecutive patients who underwent RFA of single ACs in Tel Aviv Sourasky Medical Center between 1992 and 2009 (n = 574) as well as the first consecutive 230 patients who underwent RFA of single ACs in Sheba Medical Center between 1992 and 2001 were included in this study.
The epidemiological data were collected from the patients’ medical files, and the intra-procedural results were extracted from the electrophysiology reports. AC location was characterized based on standard anatomical classification .
3 Statistical analysis
All continuous variables were presented as mean and standard deviation and all categorical variables were presented as number of patients and percentages. For categorical variables the comparisons were done using the chi-square analysis or the Fischer exact test, and for continuous variables using independent student’s t test. For all statistical analyses p value < 0.05 was considered statistically significant. The SPSS statistical package was used to perform all statistical analyses (SPSS Inc., Chicago, IL, USA).
4.1 Patient cohort
A total of 804 patients (511 male and 293 female, mean age 34 ± 16 years) who underwent their first RFA of single AC were included in this study. Among the 804 patients, 731 (90.9 %) were Jewish and 73 (9.1 %) were non-Jewish (mostly Arabs).
4.2 Anatomical distribution of accessory connections
Anatomical distribution of accessory connection
No. of patients
Left free wall
Right free wall
4.3 Accessory connection location by gender
Accessory connection location by gender
Right free wall
Left free wall
Accessory connection location by gender among Jewish patients
Right free wall
5.1 Gender difference in accessory connection location
To date, this is the largest study that showed a clear association between the AC location and patient gender. Our findings show that among Israelis right free wall ACs predominate in women while right anteroseptal ACs predominate among men. These findings were significant in the subgroup of Jewish patients. It should be noted that among the non-Jewish patients there was no statistical correlation between the AC location and the gender, but this may result from the small number of patients in this subgroup.
Our findings are in accordance with the results of the study by Hsu et al. , who compared race and gender with AC location in 282 American patients from the San Francisco area. They found that 57 % of females had right annular AC compared to 32 % of males (p < 0.001) and that patients of Asian origin had 3.8-fold greater odds of having right anterior AC compared to other races. Similar results to that observed in the Asian patients in the study of Hsu et al.  were found in a Taiwanese study, in which 30 % of the patients had right anterior located ACs . It should be noted that in our population there was a marked lower incidence of right-sided ACs in comparison to other studies cited above, which may indicate racial differences. Although there are different percentages between the races, gender differences are noted in all the races studied.
5.2 Genetic evidence in the formation of accessory connections
So far, WPW syndrome was not considered to be a familial syndrome, although significant minority of cases resulted from inherited diseases or occurred as part of a syndrome with genetic bases. Segregation analysis in normal population provides evidence for the polygenic influence on the AV conduction but no support for a single major gene [8, 9]. There are also data regarding genetic mutations causing ventricular pre-excitation: Arad et al.  over-expressed mutant human PRKAG2 cDNA under the cardiac-specific alpha-myosin heavy chain promoter. The transgenic mouse model recapitulated many phenotypic characteristics of human familial WPW . Gollob et al.  studied 70 members of the two families, 31 of them had WPW syndrome. They identified a missense mutation in the gene that encodes the ã2 regulatory subunit of AMP-activated protein kinase (PRKAG2). . Thus, it is reasonable to suggest that there is a substantial genetic role in the evolution of ACs, and our data may add another layer to this assumption.
5.3 Study limitations
(1) This is a retrospective cohort analysis. (2) Our population study is rather representative of the Tel Aviv area (90.9 % of Jewish patients) than representative of the whole Israeli population (#78 % of Jewish patients). (3) The findings are restricted to symptomatic patients who agree to RFA.
Our results shows that in our Israeli population, females more commonly have right free wall ACs and males more commonly have right anteroseptal ACs. Such findings suggest the possibility of a genetic component in the pathogenesis of AC formation.