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224 Internacional Journal of Cardiovascular Sciences. 2015;28(3):224-233

ORIGINAL MANUSCRIPT

Wolff-Parkinson-White Syndrome and : Events Predictors Lenises de Paula van der Steld, Mario de Seixas Rocha Escola Bahiana de Medicina e Saúde Pública – Salvador, BA – Brazil

Abstract

Background: The PRKAG2 syndrome is classified as a glycogen storage disease, characterized by the presence of the Wolff-Parkinson-White syndrome (WPW), ventricular hypertrophy (VH) and conduction system disease (CSD). Objectives: Finding potential prognostic factors for events in individuals affected by this disease and describing the clinical characteristics. Methods: Sixty individuals were monitored from March 2005 to March 2015, being divided into two groups: Group 1 (G1) - patients with WPW, VH or both; and Group 2 (G2) - asymptomatic patients, with normal physical examination, electrocardiogram and . It included the performance of medical history, physical examination, electrocardiogram and echocardiogram. Holter and electrophysiological study were performed when necessary. Results: G1 was made of 18 out of the 60 patients selected. Of these, 11 (61.1%) had VH related to WPW, 6 (33.3%) had isolated WPW and 1 (5.6%) patient had isolated VH. The mean age was 27.0±16.0 years and 32 (53.3%) were male. Only the patients in Group 1 had isolated events: 3 (17.0%) cardiac arrests, 2 (11.0%) sudden deaths, 6 (33.0%) pacemaker implants, 4 (22.0%) transient ischemic attacks and 9 (50.0%) combined events. The events predictors in potential combined were: left size (p=0.07) diabetes mellitus (p=0.05) and the atrioventricular blocks (p=0.019). Those factors did not have statistic significance when compared in the Cox regression analysis. Conclusions: In WPV patients with ventricular hypertrophy there was an association of diabetes mellitus, and left atrium size with the main outcomes.

Keywords: Hypertrophy, left ventricular; Wolff-Parkinson-White syndrome; Death, sudden, cardiac

Introduction patients with the disease. Ten mutations related to the gene PRKAG22,3 were described so far. The PRKAG21 syndrome was first described as a metabolic , characterized by the association of the The literature reports great polymorphism related to triad: familiar-type Wolff-Parkinson-White syndrome mutations in the gene PRKAG2, as well as cognitive (WPW), ventricular hypertrophy (VH) and conduction alterations and DM in patients of advanced age4. From system disease (CSD). Those findings can be related or the electrophysiological perspective, the presence of isolated. The WPW syndrome occurs in approximately accessory pathways (AP) of the nodo-fascicular or 50.0-100% of the patients affected by the disease, in ventricular type, with anterograde decremental addition to frequent supraventricular , conduction, was described at first. The presence of including the atrial (AF). The CSD occurs in multiple AP was not much reported in the literature so approximately 30.0-76.0% and VH, in 26.0-74.0% of the far5-7.

Corresponding author: Lenises de Paula van der Steld Av Antonio Carlos Magalhães, 585 salas 209/10 – Ed Louis Pasteur – Itaigara – 41825-000 – Salvador, BA – Brazil E-mail: [email protected]

DOI: 10.5935/2359-4802.20150032 Manuscript received on April 7, 2015; approved on June 21, 2015; revised on July 06, 2015. Int J Cardiovasc Sci. 2015;28(3):224-233 van der Steld e Rocha 225 Original Manuscript WPW and Ventricular Hypertrophy

In Brazil, Sternick et al.8,9 described two families with Afro-descendants and Indigenous short PR interval, Mahaim fibers and CSD and, recently, people, and patients of the association ABBREVIATIONS AND ACRONYMS van der Steld et al.10 described a new mutation in the gene of the WPW syndrome, VH and/or CSD. PRKAG2 related to , congestive failure All of them have been through clinical • AF – and multiple AP. history, physical examination, ECG and • AFL – uni- and bi-dimensional Color Doppler • AH – arterial hypertension Different from the hypertrophic cardiomyopathy echocardiogram (ECO). After that, they • AP – accessory pathway (HCM), caused by a sarcomeric protein mutation, the were monitored at every three months • AT – atrial PRKAG2 syndrome includes a deposit of glycogen in with visits to cardiologists, ECG and the vacuole11. The VH manifests itself after the second annual ECO. • AVB – atrioventricular block decade of life and the WPW syndrome shows alterations • CA – cardiac arrest in the electrocardiogram (ECG) from the childhood. In The relatives of the four generations • CO – combined outcomes the absence of CSD, the is made were divided by phenotypic expression • CSD – conduction system mainly with the Pompe disease, the Danon disease and in Group 1 (G1) or patients of the disease the mitochondrial myopathies vertically transmitted12,13. disease: patients with at least one of the • ECG – electrocardiogram following characteristics: symptomatic, • ECO – transthoracic The description of fatal and nonfatal events predictors abnormal physical examination, echocardiography not related to the PRKAG2 syndrome remains as a gap abnormal ECG and/or ECO; and Group • ICF – Informed Consent Form in the literature. 2 (G2) or control group: apparently normal, asymptomatic patients, with • IVS – This study aimed at finding risk predicting factors in normal physical examination, ECG and • LA – left atrium potential for cardiac events in patients of the association ECO. • LVEF – left ventricular of the WPW syndrome, VH and CSD. Furthermore, ejection fraction describing the clinical, electrocardiographic, The diagnosis of the syndrome of WPW • PM – pacemaker echocardiographic characteristics of a familiar cohort in was based on the presence of palpitation • PW – posterior wall patients of this disease. associated to supraventricular tachycardia (SVT) and short PR interval • S – stroke ECG, delta wave, morphological changes • SD – sudden death Methods of QRS complexes and of the ventricular • SVT – supraventricular re-polarization. tachycardia Prospective study of familiar cohort, monitored in private • TIA – transient ischemic attack hospital, serviced by the Unified Health System, in The VH was diagnosed by the • VF – Salvador, BA, Brazil, from March 2005 to December 2015. echocardiographic criteria of increase of the diffuse or segmental asymmetrical • VH – ventricular hyper- trophy The project was in compliance with the principles of the left ventricular mass, with no dilation of • VT – Helsinki Declaration. The study was approved by the chamber, thickness of the interventricular septum (IVS) or of the posterior wall • WPW – Wolff-Parkinson- Research Ethics Committee from the Hospital São Rafael White syndrome under no. 03/10 and by the Research Ethics Committee (PW) of the left larger than from the Escola Bahiana de Medicina e Saúde Pública 13 mm and thickness between 11-13 mm, under no. 165.803. All patients signed the Informed with or without ratio between IVS/PW >1.3, with no Consent Form, under the Resolution CNS 466/12. apparent cause.

The patients selected got to the hospital in spontaneous Heart excitoconductor system disease characterized as the demand, due to the symptoms, and in active search, full or partial interruption of the conduction passage recruited through telephone calls, being included in the through the heart conduction system, causing , study after signing the Informed Consent Form. The atrioventricular block (AVB) or interventricular blocks. individuals who failed to answer the call, refused to participate in the study, failed to sign the Informed The laboratory examinations included blood count, blood Consent Form and the patients of the glucose, total cholesterol and fractions, triglycerides, were not included. glycated hemoglobin and urine analysis summary, at every three months or if required. All the patients were The accessible population was made of four-generation through three serologic tests for Chagas disease family members, descending from a mix of Caucasian, including: hemagglutination, immunofluorescence and 226 van der Steld e Rocha Int J Cardiovasc Sci. 2015;28(3):224-233 WPW and Ventricular Hypertrophy Original Manuscript

ELISA (Enzyme-Linked Immunoabsorbent Assay). ECG statistic program SPSS version 14.0 (SPSS Inc, Chicago, of 12 simultaneous derivations was performed using the IL, USA) and R 2.15.2 was used. Micromed Model 300G electrocardiograph machine (Louisville, KY, USA). Results The ECO was performed every year by two independent observers, using uni and bi-dimensional Color Doppler Out of the total of 84 patients in the cohort, 24 were echocardiography machine of the make model Vivid 7 excluded, with 60 (71.4%) people studied remaining. The GE Healthcare (Horten, Norway). Performance of cohort is made of patients with mean age 27.4±16.2, not Caucasian (100.0%), with elementary and high school 24-hour Holter when required for diagnosing arrhythmia, education level, hypertensive (n=12; 20.0%) with a few by using DMS do Brasil recorders, with three simultaneous smokers (n=4; 4.6%), diabetic (n=3; 5.0%) and with derivations. discrete predominance of men (n=37; 53.0%). 1 – Dependent variables: Sudden death (MS), cardiac arrest (CA), transient G1 was made of 18 (30.0%) out of the total of 60 patients ischemic attack/stroke (TIA/S), pacemaker studied. Of these, 11 (18.3%) had WPW related to VH (PM); Combined outcomes (CO): upon the existence and CSD; 6 (10.0%) had isolated WPW and 1 (1.6%) of one or more out the following outcomes: SD, CA, patient had isolated VH. TIA/S or PM. 2 – Independent variables: The main symptoms were: palpitation (n=17; 28.3%), • Clinic: age, gender, palpitation, dizziness, dizziness (n=14; 23.3%), dyspnea (n=14; 23.3%), myalgia, , pre-syncope, syncope, (n=14; 23.3%), chest pain (n=13; 21.7 %), myalgia (n=2; dyspnea, systemic arterial hypertension (SAH); 3.3%), pre-syncope (n=13; 21.7%), syncope (n=14; 23.3%). • Electrocardiographic: PR interval, duration of QRS The symptoms palpitation, dizziness and syncope complexes, QTc, pauses ≥2.0s, SVT, ventricular preceded the three cardiac arrests documented in the tachycardia (VT), atrial fibrillation (AF), atrial electrocardiograph. G1 included cardiac murmurs of flutter (AFL), (AT), pauses, AVB several degrees, for 8 (44.4%) in the systolic mitral focus, of I, II, III degree; and 5 (27.8%) in the sistodiastolic aortic focus. • Echocardiographic: left atrium (LA) size, PW thickness and IVS, left ventricular ejection fraction The main electrocardiographic findings were: (LVEF). (n=17; 28.3%), SVT (n=14; 23.3%), pauses (n=6; 10.0%), short PR interval (n=3; 5.0%) morphology of right bundle Statistical analysis branch block (RBBB) (n=9; 15.0%), morphology of left (LBBB) (n=7; 11.5%), AF (n=8; 13.3%) The categorical variables were expressed in percentages, AFL (n=8; 13.3%), AT (n=7; 11,7%), full AVB (n=2; 3.3%), and the continuous variables, in average±standard VT not sustained (n=1; 1.7%). The main echocardiographic deviation, medians and interquartile interval (IQI) of not measures were: LA: 33.2±8.5; PW: 10.0±8.5; IVS: 11.0±7.6; normal distribution, and compared in the chi-square test and LVEF: 72.0±8.8. or Fisher’s exact test. The Shapiro-Wilk test was used for testing the variables normality. The genogram showed a dominant autosomal hereditary disease. Out of the 84 patients in the cohort, 18 were from The survival and other outcomes were assessed with the G1 (Figure 1). comparative Kaplan-Meier curves, between G1 and G2. In the G1 patients, the outcomes were compared in The symptoms started in the childhood, being intensified relation to the several variables. The log-rank test was as the age increased, as well as the complications. Three used for the comparison between the groups. The patients of WPW associated to VH (II.7, II.10 and II.15), multivariate analysis of Cox was performed for the reported spontaneous abortions and early fetal death up independent predictors in potential. The analysis to the third month of life. included the variables whose univariate model had significance ≤0.10. The variable remaining with The asterisk identifies the children with deafness, significance of p<0.05 was considered as independent physical hypo-development, speech and learning predictor. The results were expressed as hazard ratio disabilities. In the first and second generations, patients with the respective confidence intervals of 95%. The (I.1) and (II.4) had sudden death preceded by palpitation Int J Cardiovasc Sci. 2015;28(3):224-233 van der Steld e Rocha 227 Original Manuscript WPW and Ventricular Hypertrophy

crisis, at the age of 37 and 27, respectively. They both had Electrocardiographic findings the electrocardiographically based diagnosis of WPW During the 10-year follow-up, G2 had bradycardia in syndrome. The patient (II.20) with WPW died in a car 4 (9.5%) patients and RBBB in 1 (2.4%); all the other clinic, accident. Out of the 15 surviving patients from G1, electrocardiographic and echocardiographic variables 14 were patients with WPW and VH. The patient (III.45) remained as normal. had VH associated to CSD.

There was a progressive standard of electrocardiographic There was no difference statistically significant regarding changes in the children of G1, with short PR interval and the variables age, gender, presence of VT, PW thickness delta wave with later development of morphology of to the echocardiogram. All the other variables assessed intraventricular blocks including the enlargement of the presented statistically significant difference, while comparing groups G1 and G2 (Table 1). QRS complexes QRS, tachy- and bradyarrhythmia.

In group G1 the following symptoms prevailed: The PR interval was shorter in group G1 (85.0±7.0; palpitation, dyspnea, dizziness, myalgia, chest pain, p=0.001) compared to G2 (129.0±38.2; p=0.001); the QRS pre-syncope, syncope and the factors related: SAH, DM complexes were more enlarged in G1 (114.0±36.1) than and smoking, which contributed to the increase in the in G2 (82.0±28.3) (p=0.001); the QT interval corrected was number of events. longer in G1 (358.0±53.9) (p=0.001) (Table 1).

It was observed that group G1 had the shortest PR Out of the 15 surviving patients in G1, 8 (44.44%) had interval, the most enlarged QRS complexes, the longest RBBB standard and 7 (38.88%), the LBBB standard. The QTc interval. Only G1 included AVB, as well as brady- arrhythmia found only in G1 was: SVT (n=14; 77.77%), and tachyarrhythmia. Regarding the ECO, group G1 had VT (n=1; 5.55%); AF (n=8; 44.44%); AT (n=6; 33.33%); lower FEVE and larger IVS thickness than group G2. AFL (n=8; 44.44%); CHB (n=2; 11.11%) (Table 1).

Figure 1 Family genogram 228 van der Steld e Rocha Int J Cardiovasc Sci. 2015;28(3):224-233 WPW and Ventricular Hypertrophy Original Manuscript

Table 1 Characteristics of the population studied, per groups

G1 G2 value of p n=18 n (%) n=42 n (%)

Age (years) (average±SD) 29.5 ± 15.9 26.4 ± 16.5 0.794

Females 11 (61.11) 17 (40.47) 0.167

Smoking 4 (22.22) 1 (2.38) 0.025

Palpitation 16 (88.88) NE <0.001

Dyspnea 13 (72.22) 2 (4.76) <0.001

Dizziness 13 (72.22) 2 (4.76) <0.001

Myalgia 2 (11.11) NE <0.001

Chest pain 12 (66.66) 1 (2.38) <0.001

Pre-syncope 13 (72.22) NE <0.001

Syncope 15 (83.33) NE <0.001

SAH 8 (44.44) 4 (9.52) 0.013

DM 3 (16.66) NE 0.014

PR Interval (average±SD) 85.0±7.0 129.0±38.2 <0.001

QRS Complexes (average±SD) 114.0±29.7 82.0±28.3 <0.001

QTc (average±SD) 454.0±36.1 358.0±53.9 <0.001

RBBB 8 (44.44) 1 (2.38) <0.001

LBBB 7 (38.88) NE <0.001

Bradycardia 13 (72.22) 4 (9.52) <0.001

Pauses 6 (33.33) NE <0.001

Atrial fibrillation 8 (44.44) NE <0.001

Atrial tachycardia 6 (33.33) NE <0.001

Atrial flutter 8 (44.44) NE <0.001

Supraventricular tachycardia 14 (77.77) NE <0.001

Ventricular tachycardia 1 (5.55) NE 0.30

Total CHB 2 (11.11) NE <0.001

Left atrium 38.3±9.0 31.4±7.1 0.103

Posterior wall 12.7±4.1 8.9±2.4 0.085

Interventricular septum 14.3±4.7 9.8±8.3 0.011

Ejection fraction 66.6±12.3 74.5±5.5 0.011

AVB – atrioventricular block; RBBB – right bundle branch block; LBBB – ; DM – diabetes mellitus; AH – arterial hypertension; G1 – group of patients of the disease; G2 – group of patients apparently healthy; NE – no event; QTc – QT interval adjusted; SD – standard deviation Int J Cardiovasc Sci. 2015;28(3):224-233 van der Steld e Rocha 229 Original Manuscript WPW and Ventricular Hypertrophy

Echocardiographic findings Figure 2 shows the layout of the patient (III.27), male, who had his first CA episode at the age of 16, due to Only G1 had the asymmetrical septal hypertrophy pre-excited AF, that degenerated into VF and was subject remodeling standard (medium and high), with increase to successful cardiorespiratory reanimation. The patient in the PW thickness and IVS from the second decade of remained with severe arterial and sinus life and statistically significance. The average of IVS in bradycardia of 30 bpm. He recovered the hemodynamic G1 was 16.0±4.9 (p=0.011) and LVEF was lower in G1 stability after 24 hours, with the infusion of physiologic (66.3±8.9; p=0.011) than in G2. No patient had PW or IVS solution, (0.04 mg/kg/dose) and intravenous >30 mm. , in the dose of 10 mg/kg/day.

Two patients from G1 developed left ventricular systolic The second CA episode occurred with the same patient dysfunction, at the age of 22 (III.47) and 34 (III.22), (III.27), at the age of 20, due to following the use respectively, due to tachycardiomyopathy and of intravenous amiodarone (10 mg/kg), for treating following AFL with AV conduction 2:1. After the common atrial flutter 1:1 with ventricular rate of 300 bpm. treatment with electrical , furosemide, After a new cardiorespiratory reanimation, he underwent carvedilol and spironolactone, LVEF was normalized the implant of provisional PM, due to severe sinus in both cases. bradycardia, removed 48 hours after the event. All the CA events were preceded by atrial tachyarrhythmia (AF Except for LVEF and IVS, the other echocardiographic and AFL) associated to the symptoms palpitation, pre- variables did not present significant difference. The syncope and syncope. presence of light to moderate mitral and tricuspid regurgitation was also observed in group G1. TIA/S TIA occurred in 4 (22.0%) patients of VH, WPW, AF, AFL Isolated outcomes found only in the G1 patients: SD, and SAH (II.9; I.12; III.22; III.59). Three out of these recovered CA, TIA/S and PM implants. patients had DM. Combined outcomes: when one or more of the following outcomes occurred: SD, CA, TIA/S and/or PM. Pacemaker implants In group G1, SD and CA occurred in 4 (22.2%) patients, There were 6 (33.0%) PM implanted, being one dual TIA/S in 4 (22.2%), while those findings were null in chamber implantable cardioverter defibrillator, in patient G2 (p=0.002). PM was implanted in 6 (33.3%) G1 (II.7), due to VH, obstruction in the left ventricle outflow patients. tract, associated to VT and pre-excited AF.

The survival rate was lower in G1, in comparison to G2 Combined events (CE) (50.0% vs. 0.0%, respectively (p=0.0001). The presence of CE was found only in G1, in 9 (50.0%) patients of the group, and it can be said that the disease Cardiac arrest recovery and documentation causes a great predisposition to the development of fatal There were three CR episodes in two patients of WPW or nonfatal events. associated to VH. The patient (II.10) had a CA episode at the age of 51, due to pre-excited AF, that degenerated Univariate analysis into ventricular fibrillation (VF), during the positioning There was higher prevalence of outcomes with statistic of the atrial electrode of the definitive artificial pacemaker significance in the patients from G1, compared to those (PM) implant, indicated due to the severe sinus in G2. bradycardia and cardiogenic shock (HR=20 bpm). Cardiorespiratory resuscitation procedures were Figure 3 shows the Kaplan-Meier survival curves for followed, with respiratory ventilation and 300 J shock, the patients from G1 and G2, who survived free from with reversal to the . No neurological the combined events, stressing their crossing. This consequences occurred. After that, the electrode was shows the change in the survival and its impact between implanted to the right ventricle and the patient had a having the disease or not. The age considered for the hemodynamic recovery. statistical analysis, lower or higher than the median of 230 van der Steld e Rocha Int J Cardiovasc Sci. 2015;28(3):224-233 WPW and Ventricular Hypertrophy Original Manuscript

Figure 2 Layout of the cardiorespiratory arrest mechanism of the patient (III.27), 16 years. Pre-excited atrial fibrillation.

27 years, did not discriminate the higher incidence of 23.400–26.600; the presence of CHB with events occurring combined outcomes (SD, CA, TIA/S, PM implants). No in average at the age of 40.0, ranging between 25-56 years, statistically significant difference was presented by the log-rank (p=0.045) and CI 95%: 24.000–26.000; and the gender. average size of the LA of 39.0 mm (p=0.07) and CI 95%: 15.12–33.938. The other variables had no statistic The factors related to the combined event found in the significance. univariate analysis were: DM, with events occurring in average at the age of 27, ranging between 21-34 years, Some variables presenting biologic plausibility to the with a significance level (log-rank) of p=0.05, CI 95%: occurrence of CE had no statistical significance in this Int J Cardiovasc Sci. 2015;28(3):224-233 van der Steld e Rocha 231 Original Manuscript WPW and Ventricular Hypertrophy

cohort, through the univariate analysis. This was the case Discussion of AF, AFL and pauses, documented as CA physiopathologic mechanisms, but not revealing The WPW syndrome with is rare statistically significant data. but even rarer is the association with CHB, loss of conduction through normal tract (VA node) and of AP, Multivariate analysis - Cox regression found in most of the patients from the G1 of this cohort. Although the genetic analysis not being presented, the The Cox model was used for determining the relative phenotypic findings described confirm the suspect of the impact of the prognostic predictors. This model included PRKAG2 syndrome, described by Gollob et al.1, as a all the variables with p<0.10 in the univariate analysis. myopathic degenerative process caused by the deposit The factors DM (p=0.201), CHB (p=0.180) and LA (p=0.475) of glycogen1,8. lost their statistic significance. No factor analyzed remained as predictor independent from CE (Table 2). In group G1, the disease had predominance in the female gender and all the patients were mixed-race people. The literature has no reference to the differences regarding gender and only one author mentioned the mutation of the gene PRAKG2 in mulattos8.

Only G1 had cardiac murmurs and symptoms like palpitation, dizziness and syncope, preceding the three CA documented. Those findings agree with the descriptions by Mehdirad et al.14, of the clinic and electrophysiological characteristics of the atrioventricular connections in the WPW syndrome associated to VH.

Other interesting fact was the detection of SHA and DM more frequently in G1 than in G2 and this was also observed by Gollob et al.2 The population studied showed to the ECG, the presence of other AP besides Mahaim and predominance of short PR interval with delta wave in the childhood.

To the echocardiograph, there was a predominance of Figure 3 VH at the high and medium septum, similar to the data Curve of survival free from combined events (Kaplan- of Arad et al.15 about the VH following the glycogen Meier) in groups G1 and G2 deposits and associated to the mutations of the genes p < 0.0001; G1 = green; G2 = blue; CE – combined events PRKAG2 e LAMP2.

Table 2 Multivariate analysis: Cox regression

Variable β Wald p HR

Diabetes mellitus - 0.131 0.074 0.786 0.731

CHB -1.532 0.963 0.326 0.216

LA 0.878 0.511 0.475 2.406

LA – left atrium; AVB – atrioventricular block; HR – hazard ratio 232 van der Steld e Rocha Int J Cardiovasc Sci. 2015;28(3):224-233 WPW and Ventricular Hypertrophy Original Manuscript

All the G1 patients with DM had an episode of TIA/S. autism was also observed and not found in the literature. CHB preceded one of the documented CA episodes. In those cases, fate cannot be ruled out, but the authors Those factors were predictors in potential to the suggest the phenotypic-genotypic investigation and occurrence of CE and are associated to poor prognosis. anatomopathological examination, for the cause factor. However, the Cox regression analysis failed to prove the prognosis independence, probably due to the small size The deadly events were directly related to the presence of the sample and reduced number of events, considering of WPW, atrial tachyarrhythmia and asystole. VT was the total number of people involved and/or determiners not included in the genesis of those events. not identified, in addition to the inclusion of outcomes with different physiopathologies. Drug treatment to SAH, DM, of and invasive measures as pacemaker implants, RF ablation of SAH was present in all patients with TIA/S, but was not arrhythmias are considered as beneficial measures, able statistically significant in the univariate analysis (p=0.279). to change the evolution of those patients. Those findings were similar to the ones reported by Gollob et al.2, describing SAH associated to the mutation Limitations and perspectives (R302Q) in the gene PRKAG2 for a 23 year-old patient, A limitation of the study was the absence of genetic as well as Eosu et al.4, describing metabolic alterations analysis of the people in the cohort, which is ongoing. as DM in advanced age and cognitive disabilities in The myocardial biopsy would be very useful in patients with mutations in PRKAG2. confirming the diagnosis. On the other hand, considering the risks inherent to the procedure, the option was for No description was found in the literature about this the clinic diagnosis. syndrome equal to those in this study regarding the CE predictors in potential, the predominance of the female The small sample size and the inclusion of outcomes with gender, in addition to the electrocardiograph different physiopathologies made the multivariate documentation of three CA episodes. analysis difficult. The patients are under family genetic advising in Hospital das Clínicas de Salvador. This study observed that the LA size had a more frequent association with the CE, with statistic significance. That factor is related to atrial tachyarrhythmia, in special the Conclusions AF and AFL, which were frequent in patients of the WPW and VH association. The findings suggest that the LA In WPV patients with ventricular hypertrophy, there was size, the presence of atrial tachyarrhythmia, CHB, SAH an association of diabetes mellitus, atrioventricular block and DM confer a poor prognosis relation in that disease. and left atrium size with the main outcomes. The data found are under Mehdirad et al.14 who described metabolic alterations that affected the ionic channels and caused AF and CHB, related to the SD mechanisms in Potential conflicts of interest that disease. There are no relevant potential conflicts of interest.

As apparently incidental findings, reports by female Sources of Funding patients of WPW associated to VH with history of This study had no external funding sources. spontaneous abortions, neonatal deaths were found. The Academic Association presence of physical hypo-development, speech This manuscript is part of the Master’s thesis of Lenises de Paula alterations, poor intellectual performance, deafness and van der Steld, from Escola Bahiana de Medicina e Saúde Pública. Int J Cardiovasc Sci. 2015;28(3):224-233 van der Steld e Rocha 233 Original Manuscript WPW and Ventricular Hypertrophy

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