Abnormal Cardiac Biomarkers in Patients with Systemic Lupus Erythematosus and No Prior Heart Disease: A Consequence of Antimalarials?

Konstantinos Tselios; Dafna D. Gladman; Paula Harvey; Shadi Akhtari; Jiandong Su; Murray B. Urowitz

doi:10.3899/jrheum.171436

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Table 1.

Comparison between BNP/cTnI abnormal and BNP/cTnI normal patients.

Variables	BNP/cTnI Abnormal, n = 16	BNP/cTnI Normal, n = 135	p
Age, yrs, mean ± SD	54.7 ± 15.1	47.1 ± 12.4	0.025
Female	14 (87.5)	125 (92.6)	0.476
Male	2 (12.5)	10 (7.4)
Ethnicity
White	10 (62.5)	70 (51.9)	0.393
Black	3 (18.8)	27 (20)
Asian	3 (18.8)	18 (13.3)
Other	0	20 (14.8)
SLE duration, yrs, mean ± SD	22.54 ± 10.44	14.83 ± 9.73	0.003
SLEDAI-2K, mean ± SD	1.88 ± 2.47	2.92 ± 3.71	0.276
eGFR, ml/min, mean ± SD	82.7 ± 21.58	117.3 ± 116.4	0.003
eGFR < 30 ml/min	0 (0)	3 (2.2)	0.547
Hypothyroidism	2 (12.5)	5 (3.7)	0.114
Hypertension	10 (62.5)	45 (33.3)	0.022
Diuretics treatment	5 (31.3)	7 (5.2)	< 0.001
Mean systolic BP, mmHg, mean ± SD^§	119.58 ± 17.1	113.3 ± 12.9	0.078
Mean diastolic BP, mmHg, mean ± SD^§	72 ± 7.6	70.4 ± 8.5	0.486
Systolic BP at test, mmHg, mean ± SD	118.4 ± 21.7	113.2 ± 16.8	0.258
Diastolic BP at test, mmHg	71.9 ± 10.1	69.4 ± 12.1	0.43
Diabetes	0 (0)	7 (5.2)	0.351
Dyslipidemia	4 (25)	30 (20.7)	0.693
Abnormal CPK^*	7 (43.8)	22 (16.3)	0.008
Ever on AM	16 (100)	126 (93.3)	0.287
Ever on CQ	5 (31.3)	23 (17)	0.167
Ever on HCQ	14 (87.5)	123 (91.1)	0.638
Cumulative dose of CQ, g, mean ± SD	1509 ± 690	900 ± 287	0.003
Cumulative dose of HCQ, g, mean ± SD	1251 ± 883	1057 ± 695	0.335
Yrs taking AM, cumulative, mean ± SD	13.66 ± 9.14	7.27 ± 7.51	0.002
Taking AM > 5.6 yrs	14 (87.5)	57 (42.2)	< 0.001
Corticosteroids	8 (50)	64 (47.4)	0.844
Mean prednisone, mg/day, mean ± SD	9.4 ± 4.2	7.6 ± 5.3	0.374
Immunosuppressives	10 (62.5)	79 (58.5)	0.76

Data are n (%) unless otherwise indicated. Significant data are in bold face.
↵§ Mean value of last 4 visits.
↵* Three abnormal measurements during the last 2 years. eGFR: estimated glomerular filtration rate; BP: blood pressure; CPK: creatine phosphokinase; AM: antimalarials; CQ: chloroquine; HCQ: hydroxychloroquine; BNP: brain natriuretic peptide; cTnI: cardiac troponin I; SLE: systemic lupus erythematosus; SLEDAI-2K: SLE Disease Activity Index 2000.

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Table 2.

Univariate and multivariate analyses for assessing predictors of abnormal BNP/cTnI.

Predictor	OR	Lower 95% Confidence Limit	Upper 95% Confidence Limit	Pr > Chi-square
Univariate analysis
Age at test	1.047	1.002	1.094	0.0413
SLE duration at test	1.064	1.014	1.116	0.0114
eGFR at test	0.973	0.954	0.991	0.0039
Hypertension at test	3.025	1.042	8.776	0.0417
Diuretics treatment at test	8.183	2.288	29.268	0.0012
CPK abnormal	3.951	1.346	11.598	0.0124
Cumulative AM dose	1.105	1.031	1.184	0.0045
Yrs taking AM, cumulative (> 5.6 yrs)	1.069	1.015	1.125	0.0119
Multivariate analysis
eGFR	0.978	0.957	0.999	0.0362
Diuretics	4.218	1.078	16.503	0.0386
CPK abnormal	4.624	1.221	17.511	0.0242
Yrs taking AM, cumulative (> 5.6 yrs)	5.431	1.14	25.881	0.0337

eGFR: estimated glomerular filtration rate; CPK: creatine phosphokinase; AM: antimalarials; BNP: brain natriuretic peptide; cTnI: cardiac troponin I; SLE: systemic lupus erythematosus.

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Table 3.

Investigations of patients with abnormal heart biomarkers and no history of heart disease or pulmonary arterial hypertension.

Age/sex	Biomarkers	ECG	TTE	cMRI	Outcome
74/F	cTnI, BNP, CPK	RBBB, LAFB, LQT	LVH, RVH, LA, RA, IVSH, DD, LVEF = 30%	LVH, RVH, LA, RA, IVSH	Heart biopsy was pathognomonic for AMIC. AM discontinuation led to steady decrease of both cTnI and BNP and regression of hypertrophy.
63/F	cTnI, BNP, CPK	RBBB, LAFB	LVH, RVH, LA, IVSH, DD	LVH, RVH, LA, IVSH, LGE nonvascular	Heart biopsy was pathognomonic for AMIC. AM discontinuation led to steady decrease of both cTnI and BNP and regression of hypertrophy.
74/F	cTnI, BNP, CPK	First-degree AVB	LVH, LA, IVSH, DD	LVH, RVH, LA, RA, IVSH	Normal coronary angiography. Patient succumbed from refractory heart failure, complicated with septic shock. Possible AMIC.
59/F	cTnI, BNP	Normal	LVH, IVSH, LA, RA, DD	LVH, IVSH	Regression of hypertrophy and decrease of heart biomarkers after 6 months. Possible AMIC.
49/F	cTnI, BNP, CPK	RBBB	LVH, RVH, IVSH, LA, DD	LVH, RVH, IVSH, LA	Regression of hypertrophy, all biomarkers normalized after 12 months. Possible AMIC.
67/F	cTnI, BNP, CPK	Atrial fibrillation	LVH, LA, IVSH, DD	LVH, IVSH, LA	Possible AMIC, biomarkers at the same levels after 3 and 6 mos (AM not discontinued until later).
49/M	cTnI, BNP	Normal	LVH, LA, IVSH, DD	ND	Coronary artery disease (2 vessels), biomarkers unchanged after 6 mos (AM not discontinued).
57/F	cTnI, BNP, CPK	Nonspecific T abnormality	LVH, IVSH, regional hypokinesis, LVEF = 55%	LVH, LGE nonvascular, edema	Myocarditis. Treatment with cyclophosphamide and glucocorticoids led to regression of edema in cMRI. Partial decrease of biomarkers.
30/F	BNP	Normal, right axis deviation	RVH, RVSP = 69 mmHg	ND	PH. Treatment with phosphodiesterase-5 inhibitors led to normalization of BNP after 6 mos.
38/F	BNP	Normal	Small pericardial effusion, RVSP = 44 mmHg	ND	Patient had nephrotic syndrome owing to active lupus nephritis. Elevated BNP was attributed to volume overload.
71/F	BNP	Possible LVH, incomplete RBBB	LVH	LVH	Uncontrolled hypertension. BNP remained at the same levels despite intensive treatment after 6 and 12 mos. Cardiac troponin was marginal and remained unchanged at the same time.
71/F	BNP	Atrial fibrillation, Possible LA enlargement	LA enlargement, moderate MV regurgitation	LA, LVH	No specific cause identified. BNP remained at the same levels after 6 months. AM dose was decreased.
44/F	BNP, CPK	Possible biatrial enlargement	Mild global hypokinesis of the LV, LVEF = 45%	ND	No specific cause identified. Coronary CT with Agatston score 0. BNP remained in the same levels after 6 and 12 mos.
52/F	BNP	Normal	Normal	Normal	No specific cause identified. BNP remained in the same levels after 6 and 12 mos.
64/F	BNP, CPK	RBBB, possible LVH	Normal	ND	No specific cause identified. BNP remained in the same levels after 3, 6, and 12 mos.
48/M	cTnI, BNP	Nonspecific T abnormality	Normal	ND	No specific cause identified. BNP and cTnI were slightly decreased (still abnormal) after 6, 9, and 12 mos

ECG: electrocardiogram; TTE: transthoracic echocardiogram; cMRI: cardiac magnetic resonance imaging; cTnI: cardiac troponin I; BNP: brain natriuretic peptide; CPK: creatine phosphokinase; RBBB: right bundle branch block; LAFB: left anterior fascicular block; LQT: long QT; LVH: left ventricular hypertrophy; RVH: right ventricular hypertrophy; LA: left atrium dilatation; RA: right atrium dilatation; IVSH: interventricular septum hypertrophy; LVEF: left ventricular ejection fraction; AM: antimalarials; AMIC: AM-induced cardiomyopathy; DD: diastolic dysfunction; LGE: late gadolinium enhancement; AVB: atrioventricular block; ND: not done; PH: pulmonary hypertension; RVSP: right ventricular systolic pressure; CT: computed tomography.