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Background/Introduction Hydroxychloroquine (HCQ) is a widely used drug in Systemic Lupus Erythematosus (SLE). It may cause cardiac alterations which includes short term arrhythmic events (via QT interval prolongation) and medium-late term dose dependent cardiomyopathy1. The few research articles published on the medium-late term effects of HCQ in cardiac conduction disorder do not show relevant alterations. Purpose To assess the effect of HCQ in cardiac conduction in a consecutive SLE population. Methods Observational, single University hospital study of all consecutive SLE patients with an electrocardiogram (EKG) at HCQ onset and at least one EKG in follow-up, with a period of at least 3 months on HCQ treatment was performed. We assessed conduction alteration by electrocardiogram (EKG), defined as any degree of atrio-ventricular block or bundle branch block. The EKGs were gathered from the clinical history and interpreted at the beginning of the treatment and during the 15.2 years (CI95% 13.24–17.16) follow-up period. We defined cumulated HCQ (cHCQ) as the multiple of the mean annual dose of the sample. Results We studied 109 (96 women/ 13 men) SLE patients with a mean (±.SD) age of 61 ±. 2.78 years. A statistically significant association was observed between the cHCQ, and the development of cardiac conduction alterations [OR 1.1 CI95% 1.02–1.19; p=0.011] (Table & Figure). A total of 8 covariates were included. Among them, those that had the greatest influence on the development of the primary event were previous conduction alterations [OR 4.15 CI95% 6.39–624.54; p Conclusion According to our study, it seems to be an association between the cHCQ and development of cardiac conduction alterations regardless of other variables evaluated. Wider longitudinal studies are required with a protocolized EKG performance in successive visits to further analyze this association. Funding Acknowledgement Type of funding sources: None.

Funding Acknowledgements Type of funding sources: None. Introduction. Tricuspid annular plane systolic excursion (TAPSE) is a widely used parameter for the assessment of right ventricular (RV) systolic function in candidates for lung transplant (LT). However, its accuracy after surgery is not well established. In our study, we aim to evaluate the feasibility of TAPSE after LT and compare it with other classic parameters of RV function. Methods. 144 patients underwent LT between January 2014 and June 2017 in our center. Mean age was 55 years (65 % men). Double LT was performed in 65%, being most common etiology pulmonary fibrosis followed by chronic pulmonary obstructive disease. 9% of LT candidates had severe pulmonary hypertension (PH), defined as mean pulmonary artery pressure (PAP) over 45 mmHg on right heart catheterization. We retrospectively analyzed echocardiographic studies at baseline and 4 weeks after LT in 94 patients. Nine of them had prior severe pulmonary hypertension. We measured RV fractional area change (FAC) and systolic displacement of tricuspid annulus-TAPSE as main parameters of RV systolic function, as well as right atrium (RA) area. Results. We found a significant improvement in RV FAC (39 ± 9% vs. 44 ± 6%, p Conclusion. Right ventricular systolic function globally improved after LT, and this is particularly pronounced in candidates with severe PH. In contrast, TAPSE paradoxically deteriorates on post-surgery echocardiogram. According to our findings, TAPSE may not be a reliable parameter for the assessment of RV systolic function after lung transplant.

BackgroundHydroxychloroquine (HCQ) is a widely used drug in Systemic Lupus Erythematosus (SLE). It may cause cardiac alterations which includes short term arrhythmic events (via QT interval prolongation) and medium-late term dose dependent cardiomyopathy1. The few research articles published on the medium-late term effects of HCQ in cardiac conduction disorder do not show relevant alterations2-3.ObjectivesTo assess the effect of HCQ in cardiac conduction in a consecutive SLE population.MethodsObservational, single University hospital study of all consecutive SLE patients with an electrocardiogram (EKG) at HCQ onset and at least one EKG in follow-up, with a period of at least 3 months on HCQ treatment was performed. We assessed conduction alteration (CA) by EKG, defined as atrio-ventricular block, bundle branch block or QT interval prolongation. The EKGs were gathered from the clinical history and interpreted at the beginning of the treatment and during the 15.2 years (CI95% 13.24-17.16) follow-up period. We defined cumulated HCQ (cHCQ) as the multiple of the mean annual dose of the sample. A Multiple logistic regression model, adjusted by different variables according to statistical significance and clinical relevance, was performed.ResultsWe studied 109 (96 women/13 men) SLE patients with a mean (±SD) age of 61 ±. 2.78 years. A statistically significant association was observed between the cHCQ, and the development of CA [OR 1.1 CI95% 1.02-1.9; p = 0.011] (Table 1 & Figure 1). A total of 8 covariates were included. Among them, those that had the greatest influence on the development of the primary event were previous CA [OR 4.15 CI95% 6.39-624.54; p Table 1.Results of univariable and multivariable logistic regressions evaluating the association between cumulated hydroxychloroquine and the development of cardiac conduction alterations.VariableUnadjusted OR95%CIP-valueAdjusted OR95%CIP-valueCumulated hydroxychloroquine1.071.021.120.011.101.021.190.01CovariatesPrevious cardiac conduction alterations28.235.67140.540.0063.216.40624.540.00Cardiac valve disease4.711.6613.370.007.151.3138.910.02Age1.061.021.100.001.071.001.140.04Diabetes mellitus3.791.2611.410.023.440.5920.110.17Cerebrovascular disease2.951.028.500.050.100.011.030.05Chronic renal disease6.651.7724.980.054.880.6536.910.13Pulmonary Hypertension6.400.5673.580.143.840.13114.960.44Alcohol consumption6.400.5673.580.1410.590.58194.870.11Gender0.330.100.110.07Hypertension2.320.915.900.08Dyslipemia1.460.613.500.40Obesity1.850.418.320.42Smoking1.670.694.020.26Cardiac ischaemic disease2.080.3313.160.44Heart Failure5.911.3126.680.02Pericarditis2.080.3313.160.44OR: Odds Ratio; CI: ConfidenceFigure 1.Cardiac conduction alterations development according to cumulated Hydroxychloroquine dose.ConclusionAccording to our study, it seems to be an association between the cHCQ and development of CA regardless of other variables evaluated. Wider longitudinal studies are required with a protocolized EKG performance in successive visits to further analyze this association.References[1]Chatre C, Roubille F, Vernhet H, et al. Cardiac complications attributed to chloroquine and hydroxychloroquine: a systematic review of the literature. Drug Saf. 2018;41(10):919–931.[2]Costedoat-Chalumeau N, Hulot JS, Amoura Z, Leroux G, Lechat P, Funck-Brentano C, Piette JC. Heart conduction disorders related to antimalarials toxicity: an analysis of electrocardiograms in 85 patients treated with hydroxychloroquine for connective tissue diseases. Rheumatology (Oxford). 2007 May;46(5):808-10.[3]Godeau P, Guillevin L, Fechner J et al (1981) Disorders of conduction in lupus erythematosus. Frequency and incidence in a group of 112 patients (author’s transl). AnnMed Interne (Paris) 132:234–240.Disclosure of InterestsAlba Herrero-Morant: None declared, Jon Zubiaur-Zamacola: None declared, Adrián Margarida-de Castro: None declared, Raquel Pérez-Barquín: None declared, Miguel Á. González-Gay Speakers bureau: Abbvie, Roche, Sanofi, Lilly, Celgene, Sobi, and MSD, Grant/research support from: Abbvie, MSD, Janssen, and Roche, Ricardo Blanco Speakers bureau: Abbvie, Lilly, Pfizer, Roche, BMS, Janssen, and MSD, Grant/research support from: Abbvie, MSD, and Roche

Background:Hydroxychloroquine (HCQ) is an extensively used drug in immune-mediated diseases (IMID). Despite its general safety, HCQ can cause serious toxicity such as heart conduction disorders. Atrioventricular block (AVB) is an underrecognized adverse effect that can potentially cause significant morbidity and mortality.Objectives:To study incidence, presentation, and characteristics of HCQ-induced AVB in IMID.Methods:Open-label single center study of 293 patients with IMID treated with HCQ for at least 3 months. Electrocardiograms were analyzed at baseline and during HCQ treatment. In addition, a comparative study between patients with and without AVB was conducted.Results:We studied 293 patients (270 women/ 23 men; mean age 59.7±14.7 years). Underlying IMID were Systemic Lupus Erythematosus (SLE) (n=109, 40.6%); undifferentiated connective-tissue disease (n=70, 23.9%), Sjögren’s syndrome (SS) (n=70, 23.9%), antiphospholipid syndrome (n=31,10.6%) and other IMID (n=13, 4.4%). HCQ was used for 4.1±3.5 years.After 11.8±8.9 years of follow-up (HCQ mean cumulative dose: 979.7±272.1 g). AVB was observed in 19 out of 293 (6.5%) patients: 16 (84.2%) were first-degree AVB and 3 (15.8%) complete AVB. 4 (21.2%) patients with AVB were treated with a permanent pacemaker.Presentation of atrioventricular block according to hydroxychloroquine incidence rate and treatment duration is shown in Figure 1. Most of AVB happened in the first 40 months, regardless of HCQ cumulative dose.Figure 1.Presentation of atrioventricular block according to hydroxychloroquine incidence rate and treatment duration.A comparative study between patients with and without AVB was performed (Table 1). Patients with AVB were older (p=0.014) and had a higher incidence of diabetes mellitus (p=0.033). HCQ cumulative dose and duration of IMID were similar in both groups (p>0.05).Other HCQ adverse effects were retinopathy (n=16, 5.4%), gastrointestinal alterations (n=14, 4.8%), cutaneous alterations (n=14, 4.8%), allergic reactions (n=4, 1.4%) and myopathy (n=1, 0.3%).Conclusion:AVB was observed in 6.5% of patients with IMID treated with HCQ. Most AVB were first-degree AVB. HCQ increased the risk of developing an AVB in patients with IMID regardless of HCQ cumulative dose or underlying disease duration. Older patients with diabetes mellitus had a higher risk of developing an AVB.Table 1.Comparative study between patients with and without AVB.with AVBn= 19without AVBn = 274pGeneral features at HCQ onsetAge, years mean±SD57.4±14.546.4±16.80.014Female, n (%)17(89.5)239(87.4)0.877Hypertension, n (%)14 (73.7)149 (54.4)0.118Dyslipemia, n (%)11 (58.9)117 (42.7)0.265Diabetes Mellitus, n (%)5 (26.3)24 (8.7)0.033Renal impairment, n (%)5 (26.3)29 (10.7)0.073Ischemic cardiopathy, n (%)2 (10.5)11 (3.9)0.228CRP, mg/dL median [IQR]0.3 [0.1-0.5]0.4 [0.3-0.8]0.343ESR, mm/h median [IQR]17.0 [15.0-22.3]13.0 [7.0-29.5]0.206Data at last visit (11.8±8.9 years of follow-up)IMID duration, years mean±SD11.8±8.914.3±10.30.288# Use of other cardiotoxic drugs, n (%)2 (10.5)11 (4.0)0.723HCQ cumulative dose, g mean±SD813.2±206.0996.3±266.90.527# (beta blockers, calcium channel blockers, tricyclic drugs, other AVB inducers)Disclosure of Interests:Alba Herrero-Morant: None declared, Adrián Margarida-de Castro: None declared, Raquel Pérez-Barquín: None declared, Jon Zubiaur-Zamacola: None declared, Miguel Á. González-Gay Speakers bureau: AbbVie, Pfizer, Roche, Sanofi, Lilly, Celgene and MSD, Grant/research support from: AbbVie, MSD, Jansen and Roche, Ricardo Blanco Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, Sanofi, Lilly and MSD, Grant/research support from: AbbVie, MSD, and Roche

Background:Hydroxychloroquine (HCQ) is a widely used drug especially in connective tissue disorders such as Systemic Lupus Erythematosus (SLE). Cardiac adverse effects of long-term use of HCQ remains controversial.Objectives:To assess cardiac adverse effects of long-term use of HCQ in SLE.Methods:Observational single center study of 109 patients with SLE treated with HCQ for more than 3 months. The main outcomes were cardiac structural and conduction disorders in a 12-lead electrocardiogram and/or echocardiogram at baseline and during HCQ treatment.Results:We studied 109 patients (95 women/14 men; mean age 66.9±14.7 years). Main cardiovascular history was hypertension (n=61, 56.0%), diabetes mellitus (n=16, 14.7%) and renal impairment (n=11, 10.1%). HCQ was used for 11.7±8.9 years. Initial median SLE Disease Activity Index 2000 (SLEDAI-2K) was 7 [3.75-11]. At baseline, 27 (24.8%) patients had conduction disorders and 15 (13.7%) had structural abnormalities: Most prevalent cardiac alterations were Left Anterior Fascicular Block (LAFB) (n=9, 8.3%), left ventricular hypertrophy (n=9, 8.3%) and right bundle branch block (n=8, 7.3%). After 11.7±8.9 years of follow-up (mean HCQ cumulative dose: 1042.2±267.5 g; median SLEDAI-2K 1 [0-4]), there was a significant increase in conductions disorders (n=41, 37.6%, p=0.011) and in LAFB (n=16, 14.7%, p=0.021). There was no statistically significant increase in structural abnormalities (n=21, 19.7%, p=0.629).Main cardiac abnormalities at baseline and after 11.7±8.9 years of follow-up are summarized in Table 1. Time of occurrence of cardiac adverse effect in relation to HCQ cumulative dose is shown in Figure 1.Table 1.Main cardiac abnormalities at baseline and after follow-up.BaselineAfter follow-uppConduction disorders, n (%)27 (24.8)41 (37.6)0.011Left anterior fascicular block9 (8.3)16 (14.7)0.021Right bundle branch block7 (6.4)8 (7.3)1.0Atrioventricular block4 (3.6)11 (10.1)0.092Incomplete right bundle branch block4 (3.6)5 (4.6)1.0Short PR interval2 (1.8)4 (3.7)0.5Prolonged QT corrected interval2 (1.8)4 (3.7)0.625Left bundle branch block1 (0.9)5 (4.6)0.125Atrial Fibrillation1 (0.9)5 (4.6)0.219Structural abnormalities, n (%)15 (13.7)21 (19.7)0.629Ventricular hypertrophy9 (8.3)9 (8.3)1.0Atrial enlargement6 (5.5)13 (11.9)0.096Figure 1.Time of occurrence of cardiac adverse effect in relation to hydroxychloroquine cumulative dose.Conclusion:Conduction disorders were more prevalent than structural abnormalities. Patients with SLE treated with HCQ had a significant increase in LAFB. Use of electrocardiogram and/or echocardiogram may be helpful in monitoring cardiac adverse effects.Disclosure of Interests:Alba Herrero-Morant: None declared, Adrián Margarida-de Castro: None declared, Raquel Pérez-Barquín: None declared, Jon Zubiaur-Zamacola: None declared, Miguel Á. González-Gay Speakers bureau: AbbVie, Pfizer, Roche, Sanofi, Lilly, Celgene and MSD, Grant/research support from: AbbVie, MSD, Jansen and Roche, Ricardo Blanco Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, Sanofi, Lilly and MSD, Grant/research support from: AbbVie, MSD, and Roche