QTc interval prolongation in systemic sclerosis: Correlations with clinical variables

Abstract

Systemic sclerosis (SSc) is an autoimmune disease characterized byendothelial dysfunction and fibrosis of the skin and internal organs [1].Cardiac involvement in the course of SSc could be primary or sec-ondary to pulmonary arterial hypertension and kidney pathology. Pri-mary cardiac involvement may manifest as myocardial involvement,arrhythmias,fibrosisoftheconductionsystem,pacemakerandintracar-diac defibrillator implantation, sudden death and autonomic dysfunc-tion [2,3].Amongtheabnormalities in SSc,QTc intervalprolongation hasbeenreportedandassociatedwithanti-RNApolymeraseIIIantibodies,longerdisease duration, and greater disease severity [4].Accordingly,theaimofthestudyistoassessQTcprolongationinSScand evaluate correlations with clinical variables and complications ofthe disease.The protocol is in accordance with the Declaration of Helsinki andwas approved by the Ethics Committee at our Institution. Twenty Cau-casian subjects fulfilling the American Rheumatism Association (ARA)criteria for classification and diagnosis of SSc [5] and twenty healthysubjectswereexaminedbeforeinclusioninthestudy.All examined pa-tientsunderwentclinicalevaluation,ambulatory24-hourECGmonitor-ing, transthoracic echocardiogram.Scleroderma patients with coronary artery disease, congestiveheartfailure, left ventricular dysfunction, significant valvular abnormalitiesand arrhythmias were not included in the study.Patients with pulmonary function abnormalities were not includedeither. Patients with diabetes mellitus, renal failure, hepatic or thyroiddysfunction, and anemia were excluded.Patients were not takingβ-blockers, antiarrhythmic drugs,ACE-inhibitors or angiotensin receptor antagonists. QTc interval,assessed by 24-hour Holter ECG recording, was defined as prolongedwhen N440 ms [6].Nailfold videocapillaroscopy (NVC) was performed by an opticalprobe, equipped with magnification 200× contact lens and connectedto image analysis software (Pinnacle Studio Version 8). The identifiedpatterns were classified as early, active or late [7]. Skin thickening wasassessed by a modified Rodnan total skin score (mRSS) [8]. In all pa-tientswemeasuredtheDiseaseActivityIndex(DAI)andDiseaseSever-ity Scale (DSS) [9].Thedatawereexpressedasmedianandrange.Multivariateanalysiswas applied for the estimation of relationship of QTc with disease vari-ables. The Mann–Whitney U-test or Kruskal–Wallis were used to testdifferences between two individual study groups. Spearman's rankorder correlation coefficient (r) was used to test for an association be-tweennumericalvariables.p-Valuesb0.05wereconsideredsignificant.Commercial software (SPSS version 20.0) was used for statisticalanalysis.Twentysclerodermapatientswereenrolledinthecurrentstudy.Theepidemiological and clinical features of SSc are shown in Table 1.ThemedianvalueofQTcissignificantly(pb0.0001)increasedinSScpatients than healthy controls [447 (414–566) vs 386 (342–447)].The medianvalueof QTc is significantly (p b 0.01) different in threecapillaroscopicgroups:early425(421 –454),active437(416–467),late471 (445–566).ThemedianvalueofQTcissignificantly(pb 0.05)augmentedin SScpatients with digital ulcers than in SSc patients without digital ulcers[459(422–566)vs436(416–454)].Apositivecorrelation (p b0.05)ex-ists between QTc and mRSS (r = 0.53).NocorrelationswerefoundbetweenQTcanddiseasesubset,diseaseduration, Disease Activity Index, and Disease Severity Scale.Amongthe causes of suddencardiacdeath in SScpatients,ventricu-lar late potentials, autonomic dysfunction, pro-arrhythmogenic drugsand increased QT dispersion were found.