Systemic Lupus Erythematous and Heart Conduction Disorders

• ClinicalTrials.gov Identifier: NCT02162992
• Recruitment Status: Completed
• First Posted: June 13, 2014
• Results First Posted: October 28, 2019
• Last Update Posted: October 28, 2019
• Sponsor: Germans Trias i Pujol Hospital
• Information provided by (Responsible Party): Roger Villuendas Sabaté, Germans Trias i Pujol Hospital

Tracking Information

• First Submitted Date: April 24, 2014
• First Posted Date: June 13, 2014
• Results First Submitted Date: September 4, 2019
• Results First Posted Date: October 28, 2019
• Last Update Posted Date: October 28, 2019
• Study Start Date: April 2014
• Actual Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 4, 2019)

Presence of Conduction Disorders in Patients With SLE Regarding to Its Serologic Profile [ Time Frame: 24 hours ]

Conduction disorders will be evaluated by 12-lead ECG recordings an 24-hour Holter recordings. Measurements will include PR intervals (in msec), QRS duration (in msec) .

Original Primary Outcome Measures (submitted: June 12, 2014)

Incidence of conduction disorders in patients with SLE regarding to its serologic profile [ Time Frame: One year ]

Conduction disorders will be evaluated by 12-lead ECG recordings an 24-hour Holter recordings. Measurements will include PR intervals (in msec), QRS duration (in msec) and the presence of second or third degree atrioventricular blockade.

Current Secondary Outcome Measures (submitted: October 4, 2019)

QT and Corrected QT Intervals [ Time Frame: 24 hours ]

Ventricular repolarization will be evaluated by 12-lead ECG recordings an 24-hour Holter recordings. Measurements will include QT and corrected QT intervals, and the presence of ventricular arrhythmia. Corrected QT (QTc) intervals will be obtained by measuring the QT interval (QTm) and the previous RR interval, following the Bazett formula (QTc=QTm divided by the square root of previous RR interval in seconds). A comparison will be made between the anti-Ro60 antibody positive patients and the anti-Ro60 antibody negative patients.

Original Secondary Outcome Measures (submitted: June 12, 2014)

Association between anti-Ro60 antibody and conduction disturbances such as QT interval prolongation. [ Time Frame: 24 hours ]

Ventricular repolarization will be evaluated by 12-lead ECG recordings an 24-hour Holter recordings. Measurements will include QT and corrected QT intervals, and the presence of ventricular arrhythmia. A comparison will be made between the anti-Ro60 antibody positive patients and the anti-Ro60 antibody negative patients.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Systemic Lupus Erythematous and Heart Conduction Disorders
• Official Title: Repolarization Disorders and Heart Conduction Disorders in Patients With Systemic Lupus Erythematous
• Brief Summary: Connective tissue diseases have been related to heart conduction disorders. The anti-Ro/SSA antibodies are thought to have a pathogenic role, and they most prevalent in systemic lupus erythematous (SLE). The aim of this study is to evaluate the relationship between SLE, arrhythmias and its serologic profile.

Detailed Description

We designed a cross-sectional study for an observational analysis. The target population will be the group of SLE patients visited the service of Rheumatology hospitals in Catalonia (Spain).

The criteria for subjects selection to participate in our project are:

1 . Inclusion criteria: patients with SLE according to established diagnostic criteria in 1997 2. Exclusion criteria:

• Presence of cardiac: Ischemic heart disease or congenital or acquired structural heart disease (hypertrophic cardiomyopathy, idiopathic dilated cardiomyopathy, valve disease with clinical significance).
• Background heart surgery or cardiac ablation procedures.
• Background in other pathological processes has been described affecting cardiac conduction tissue: Steinert's disease, Lyme disease, Chagas' disease with heart involvement or hypothyroidism.

The selection of patients and controls are done through a sampling of consecutive patients seen in our outpatient rheumatology center to achieve the sample size. This has been fixed in two subgroups: 100 patients with SLE and positive for anti-Ro (with positivity for anti-Ro only 52 or positivity for anti-Ro and anti-Ro 52 60) and 50 patients (controls ) with SLE and negative for anti-Ro (anti-Ro52 and anti-Ro 60).

As defined as primary variables, the study of cardiac conduction disorders will be done through the analysis of resting electrocardiogram (ECG) and a 24-hour Holter.

Other descriptive variables are listed below:

• Collection of general medical history of patients, with emphasis on Rheumatology and cardiac involvement.
• Check the current medication.
• Height and weight.
• Physical examination.
• 12-lead resting ECG with analysis of rate base, as well as the duration of the PR interval, QRS and QT. Analysis of the presence of intraventricular conduction disorders and the presence of ectopic beats.
• Record 24-hour Holter Presence and number of ventricular ectopic beats, classification of events according to the Lown's criteria. Presence of significant pauses (RR interval> 2000mseg). Measurement of corrected QT (QTc).
• Presence of autonomic dysfunction parameters: time domain parameters such as the mean RR interval, standard deviation of all normal RR intervals (SDNN), the root of the mean difference between successive adjacent normal RR intervals (RMSSD ) and the percentage of adjacent intervals over 50mseg (PNN50)
• Echocardiography to rule out structural heart disease: Analysis of ventricular diameters and systolic and diastolic function, presence of significant valve disease, pulmonary systolic pressure, pericardial effusion and other congenital or acquired structural heart disease.
• Analysis with serologic immune profile, determining the degree of organic involvement by SLE

• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Patients with SLE visited in the rheumatology outpatient's area.

Condition

• Lupus Erythematosus, Systemic
• Atrioventricular Block
• Sudden Death

Intervention

Other: No intervention

Observational

Study Groups/Cohorts

• SLE and Anti-Ro antibodies Group
  Patients with SLE visited in the rheumatology outpatient's area. No intervention (only observational)
  Intervention: Other: No intervention
• SLE without Anti-Ro antibodies Group
  Patients with SLE visited in the rheumatology outpatient's area. No intervention (only observational)
  Intervention: Other: No intervention

Publications *

• Lazzerini PE, Capecchi PL, Laghi-Pasini F. Anti-Ro/SSA antibodies and cardiac arrhythmias in the adult: facts and hypotheses. Scand J Immunol. 2010 Sep;72(3):213-22. doi: 10.1111/j.1365-3083.2010.02428.x. Review.
• Chameides L, Truex RC, Vetter V, Rashkind WJ, Galioto FM Jr, Noonan JA. Association of maternal systemic lupus erythematosus with congenital complete heart block. N Engl J Med. 1977 Dec 1;297(22):1204-7.
• Seferović PM, Ristić AD, Maksimović R, Simeunović DS, Ristić GG, Radovanović G, Seferović D, Maisch B, Matucci-Cerinic M. Cardiac arrhythmias and conduction disturbances in autoimmune rheumatic diseases. Rheumatology (Oxford). 2006 Oct;45 Suppl 4:iv39-42. Review.
• Edwards CS, Mootoo R, Bhanji A. High grade heart block in association with SLE. Ann Rheum Dis. 2004 May;63(5):606.
• Costedoat-Chalumeau N, Georgin-Lavialle S, Amoura Z, Piette JC. Anti-SSA/Ro and anti-SSB/La antibody-mediated congenital heart block. Lupus. 2005;14(9):660-4. Review.
• Santos-Pardo I, Martínez-Morillo M, Villuendas R, Bayes-Genis A. Anti-Ro antibodies and reversible atrioventricular block. N Engl J Med. 2013 Jun 13;368(24):2335-7. doi: 10.1056/NEJMc1300484.
• Behan WM, Behan PO, Gairns J. Cardiac damage in polymyositis associated with antibodies to tissue ribonucleoproteins. Br Heart J. 1987 Feb;57(2):176-80.
• Logar D, Kveder T, Rozman B, Dobovisek J. Possible association between anti-Ro antibodies and myocarditis or cardiac conduction defects in adults with systemic lupus erythematosus. Ann Rheum Dis. 1990 Aug;49(8):627-9.
• O'Neill TW, Mahmoud A, Tooke A, Thomas RD, Maddison PJ. Is there a relationship between subclinical myocardial abnormalities, conduction defects and Ro/La antibodies in adults with systemic lupus erythematosus? Clin Exp Rheumatol. 1993 Jul-Aug;11(4):409-12.
• Lodde BM, Sankar V, Kok MR, Leakan RA, Tak PP, Pillemer SR. Adult heart block is associated with disease activity in primary Sjögren's syndrome. Scand J Rheumatol. 2005 Sep-Oct;34(5):383-6.
• Costa M, Gameiro Silva MB, Silva JA, Skare TL. Anti-RO anti-LA anti-RNP antibodies and eletrocardiogram's PR interval in adult patients with systemic lupus erythematosus. Acta Reumatol Port. 2008 Apr-Jun;33(2):173-6.
• Lazzerini PE, Capecchi PL, Guideri F, Acampa M, Galeazzi M, Laghi Pasini F. Connective tissue diseases and cardiac rhythm disorders: an overview. Autoimmun Rev. 2006 May;5(5):306-13. Epub 2005 Dec 9. Review.
• Lazzerini PE, Capecchi PL, Acampa M, Morozzi G, Bellisai F, Bacarelli MR, Dragoni S, Fineschi I, Simpatico A, Galeazzi M, Laghi-Pasini F. Anti-Ro/SSA-associated corrected QT interval prolongation in adults: the role of antibody level and specificity. Arthritis Care Res (Hoboken). 2011 Oct;63(10):1463-70. doi: 10.1002/acr.20540.
• Villuendas R, Olivé A, Juncà G, Salvador I, Martínez-Morillo M, Santos-Pardo I, Pereferrer D, Zamora E, Bayes-Genis A. Autoimmunity and atrioventricular block of unknown etiology in adults: the role of anti-Ro/SSA antibodies. J Am Coll Cardiol. 2014 Apr 8;63(13):1335-1336. doi: 10.1016/j.jacc.2013.10.086. Epub 2014 Jan 30.
• Gordon PA, Rosenthal E, Khamashta MA, Hughes GR. Absence of conduction defects in the electrocardiograms [correction of echocardiograms] of mothers with children with congenital complete heart block. J Rheumatol. 2001 Feb;28(2):366-9. Erratum in: J Rheumatol 2001 May;28(5):1200.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 4, 2019): 151
• Original Estimated Enrollment (submitted: June 12, 2014): 86
• Actual Study Completion Date: April 2018
• Actual Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients with SLE diagnosis, according to SLE diagnostic criteria.

Exclusion Criteria:

• Patients with previous cardiac diseases (ischemic heart disease, hypertrophic cardiomyopathy, dilated cardiomyopathy, valvular heart disease)
• Clinical history of heart surgery or ablation procedures

• Clinical history of other conditions that affect heart conduction:

  • Steinert Disease
  • Lyme Disease
  • Chagas Disease
  • Hypothyroidism

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT02162992
• Other Study ID Numbers: ICOR-2014-01
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Roger Villuendas Sabaté, Germans Trias i Pujol Hospital
• Study Sponsor: Germans Trias i Pujol Hospital
• Collaborators: Not Provided

Investigators

• Principal Investigator: Roger Villuendas; GTIPUH

• PRS Account: Germans Trias i Pujol Hospital
• Verification Date: October 2019