Cardiac magnetic resonance predicts ventricular arrhythmias in scleroderma: the Scleroderma Arrhythmia Clinical Utility Study (SAnCtUS).

OBJECTIVES: Cardiac rhythm disturbances constitute the most frequent cardiovascular cause of death in SSc. However, electrocardiographic findings are not a part of risk stratification in SSc. We aimed to translate 24 h Holter findings into a tangible risk prediction score using cardiovascular magnetic resonance. METHODS: The Scleroderma Arrhythmia Clinical Utility Study (SAnCtUS) was a prospective multicentre study including 150 consecutive SSc patients from eight European centres, assessed with 24 h Holter and cardiovascular magnetic resonance, including ventricular function, oedema (T2 ratio) and late gadolinium enhancement (%LGE). Laboratory/clinical parameters were included in multivariable corrections. A combined endpoint of sustained ventricular tachycardia requiring hospitalization and sudden cardiac death at a median (interquartile range) follow-up of 1 (1.0-1.4) year was generated. RESULTS: Only T2 ratio and %LGE were significant predictors of ventricular rhythm disturbances, but not of supraventricular rhythm disturbances, after multivariable correction and adjustment for multiple comparisons. Using decision-tree analysis, we created the SAnCtUS score, a four-category scoring system based on T2 ratio and %LGE, for identifying SSc patients at high risk of experiencing ventricular rhythm disturbance at baseline. Increasing SAnCtUS scores were associated with a greater disease and arrhythmic burden. All cases of non-sustained ventricular tachycardia (n = 7) occurred in patients with the highest SAnCtUS score (=4). Having a score of 4 conveyed a higher risk of reaching the combined endpoint in multivariable Cox regression compared with scores 1/2/3 [hazard ratio (95% CI): 3.86 (1.14, 13.04), P = 0.029] independently of left ventricular ejection fraction and baseline ventricular tachycardia occurrence. CONCLUSION: T2 ratio and %LGE had the greatest utility as independent predictors of rhythm disturbances in SSc patients.

CMR feature tracking in cardiac asymptomatic systemic sclerosis: Clinical implications.

BACKGROUND: Impaired myocardial deformation has been sporadically described in cardiac asymptomatic systemic sclerosis (SSc). We aimed to study myocardial deformation indices in cardiac asymptomatic SSc patients using cardiac magnetic resonance feature tracking (CMR-FT) and correlate these findings to the phenotypic and autoimmune background. METHODS: Fifty-four cardiac asymptomatic SSc patients (44 females, 56±13 years), with normal routine cardiac assessment and CMR evaluation, including cine and late gadolinium enhancement (LGE) images, were included. SSc patients were compared to 21 sex- and age- matched healthy controls (17 females; 54±19 years). For CMR-FT analysis, a mid-ventricular slice for LV peak systolic radial and circumferential strain and a 4-chamber view for LV/RV peak systolic longitudinal strain were used. RESULTS: Twenty-four patients had diffuse cutaneous SSc and 30 limited cutaneous SSc. Thirteen patients had digital ulcers. Median disease duration was 3.6 years. LV ejection fraction was higher in SSc patients compared to controls (62±6% vs. 59±5%, p = 0.01). Four patients had no LGE examination; in the remaining patients LGE was absent in 74%, while 18% had RV insertion fibrosis and 8% evidence of subendocardial infarction. LV longitudinal strain differed in those with insertion fibrosis (-18.0%) and infarction (-16.7%) compared to no fibrosis (-20.3%, p = 0.04). Patients with SSc had lower RV longitudinal strain and strain rate compared to controls (p<0.001 and p = 0.01, respectively). All other strain and strain rate measurements were non-significant between patients and controls. CONCLUSIONS: In cardiac asymptomatic SSc patients with normal routine functional indices, CMR-FT identifies subclinical presence of insertion fibrosis and/or myocardial infarction by impaired LV longitudinal strain. RV derived longitudinal indices were impaired in the patient group. CMR FT indices did not correlate to the patients' phenotypic and autoimmune features.

Cardiovascular magnetic resonance imaging pattern in patients with autoimmune rheumatic diseases and ventricular tachycardia with preserved ejection fraction.

BACKGROUND: Ventricular tachycardia/fibrillation (VT/VF) may occur in autoimmune rheumatic diseases (ARDs). We hypothesized that cardiovascular magnetic resonance (CMR) can identify arrhythmogenic substrates in ARD patients. PATIENTS - METHODS: Using a 1.5 T system, we evaluated 61 consecutive patients with various types of ARDs and normal left ventricular ejection fraction (LVEF) on echocardiography. A comparison of patients with recent VT/VF and those that never experienced VT/VF was performed. CMR parameters included left and right ventricular (LV and RV) end-systolic and end-diastolic volumes (ESV and EDV), T2 signal ratio of myocardium over skeletal muscle, early/late gadolinium enhancement (EGE and LGE), T1/T2-mapping and extracellular volume fraction (ECV). RESULTS: 21 (34%) patients had a history of recent, electrocardiographically identified, VT/VF. No demographic or functional CMR variables differed significantly between groups. The same was the case for T2 signal ratio and EGE/LGE. Median native T1 mapping values were significantly higher in patients with VT/VF compared to those without [1135.0 (1076.0, 1201.0) vs. 1050.0 (1025.0, 1078.0), p < 0.001], as was the case for mean T2 mapping [60.4 (6.6) vs. 55.0 (7.9), p = 0.009] and median ECV values [32.0 (30.0, 32.0) vs. 29.0 (28.0, 31.5), p = 0.001]. After multivariate corrections for age, LVEDV, LVEF, RVEDV, RVEF, T2 signal ratio, EGE and LGE, these remained significant predictors of having experienced VT/VF in the past. CONCLUSIONS: T1/T2-mapping and ECV offer incremental value as identifiers of arrhythmogenic substrates in ARD patients, beyond traditionally used indices. They can thus guide implantable cardiac defibrillator (ICD) implantation in ARD patients presenting with VT/VF and normal LVEF.

Silent myocarditis in systemic sclerosis detected by cardiovascular magnetic resonance using Lake Louise criteria.

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by microvascular abnormalities, inflammation and fibrosis. We hypothesized that myocarditis may be diagnosed in asymptomatic SSc, undergoing routine cardio-vascular magnetic resonance (CMR) for fibrosis assessment, using the Lake Louise criteria: T2 ratio, early (EGE) and late gadolinium enhanced (LGE) images. METHODS: Eighty-two asymptomatic SSc, diagnosed according to American College of Rheumatology criteria, aged 43 ± 5 yrs., 62 with diffuse (dSSc) and 20 with localized (lSSc) systemic sclerosis were evaluated by CMR, performed at 1.5 T scanner, according to Lake Louise criteria. RESULTS: CMR documented normal biventricular function in all SSc. However, 7/62 (11.2%) with dSSc and 2/20 (10%) with lSSc, had CMR signs of myocarditis according to Lake Louise criteria, without any clinical cardiac symptom. In these 9 patients, T2 ratio, EGE ratio and LGE (positive in all 9 SSc) were 2.8 ± 0.5%, 8 ± 3% and 5 ± 3% of LV mass, respectively. No correlation between CMR and blood inflammatory indices (C-reactive protein and erythrocyte sedimentation rate), cardiac troponin T, disease characteristics or type of SSc was identified. A repeat CMR at 6 months, after treatment with prednisone and azathioprine, showed normalisation of the acute inflammation CMR indices. CONCLUSIONS: Silent myocarditis may be diagnosed using the Lake Louise paper criteria in SSc patients without cardiac symptoms, has no correlation with blood inflammatory indices, cardiac troponin or disease characteristics. CMR is a promising tool to diagnose silent myocarditis in SSc and monitor the response to immunosuppressive treatment.

Cardiovascular magnetic resonance imaging pattern at the time of diagnosis of treatment naïve patients with connective tissue diseases.

BACKGROUND-AIM: Cardiac involvement at diagnosis of connective tissue disease (CTD) has been described by echocardiography. We hypothesized that cardio-vascular magnetic resonance (CMR) detects occult lesions at CTD diagnosis. PATIENTS-METHODS: CMR was performed early after diagnosis in 78 treatment-naïve CTDs (aged 43±11, 59F/19M) without cardiac involvement [5 Takayasu arteritis (TA), 4 Churg Strauss syndrome (CSS), 5 Wegener granulomatosis (WG), 16 systemic lupus erythematosus (SLE), 12 rheumatoid arthritis (RA), 8 mixed connective tissue diseases (MCTD), 12 ankylosing spondylitis (AS), 3 polymyalgia rheumatica (PMR), 8 systemic sclerosis (SSc) and 5 dermatomyositis (DM)]. Acute and chronic lesions were assessed by T2>2 with positive LGE and T2<2 with positive LGE, respectively. RESULTS: In 3/5 TA, 3/4 CSS, 4/5 WG, 10/16 SLE, 9/12 RA, 6/8 MCTD, 4/12 AS, 1/3 PMR, 2/8 SSc and 2/5 DM, the T2 ratio was higher compared to normal (2.78±0.25 vs 1.5±0.2, p<0.01). Myocarditis was identified in 1 TA, 1 SLE, 1 RA, 1 SSc and 2 DM patients; diffuse, subendocardial fibrosis in 1 CSS and 1 RA patient, while subendocardial myocardial infarction in 3 SLE, 1 MCTD, 1 PMR and 2 RA patients. CMR re-evaluation after 6 and 12months of rheumatic and cardiac treatment, available in 28/52 CTDs with increased T2 ratio, showed significant improvement in T2 ratio (p<0.001), non-significant change in LGE extent and normalisation of those with impaired LV function. CONCLUSIONS: Occult CMR lesions, including oedema, myocarditis, diffuse subendocardial fibrosis and myocardial infarction are not unusual in treatment naïve CTDs and may be reversed with appropriate treatment.

Cardiovascular magnetic resonance in rheumatology: Current status and recommendations for use.

Targeted therapies in connective tissue diseases (CTDs) have led to improvements of disease-associated outcomes, but life expectancy remains lower compared to general population due to emerging co-morbidities, particularly due to excess cardiovascular risk. Cardiovascular magnetic resonance (CMR) is a noninvasive imaging technique which can provide detailed information about multiple cardiovascular pathologies without using ionizing radiation. CMR is considered the reference standard for quantitative evaluation of left and right ventricular volumes, mass and function, cardiac tissue characterization and assessment of thoracic vessels; it may also be used for the quantitative assessment of myocardial blood flow with high spatial resolution and for the evaluation of the proximal coronary arteries. These applications are of particular interest in CTDs, because of the potential of serious and variable involvement of the cardiovascular system during their course. The International Consensus Group on CMR in Rheumatology was formed in January 2012 aiming to achieve consensus among CMR and rheumatology experts in developing initial recommendations on the current state-of-the-art use of CMR in CTDs. The present report outlines the recommendations of the participating CMR and rheumatology experts with regards to: (a) indications for use of CMR in rheumatoid arthritis, the spondyloarthropathies, systemic lupus erythematosus, vasculitis of small, medium and large vessels, myositis, sarcoidosis (SRC), and scleroderma (SSc); (b) CMR protocols, terminology for reporting CMR and diagnostic CMR criteria for assessment and quantification of cardiovascular involvement in CTDs; and (c) a research agenda for the further development of this evolving field.

Pseudo-infarction pattern in diffuse systemic sclerosis. Evaluation using cardiovascular magnetic resonance.

BACKGROUND: Diffuse systemic sclerosis (dSSc) is characterized by vascular lesions and fibrosis. Cardiac involvement, although silent, accounts for 36% of deaths. We hypothesized that cardiovascular magnetic resonance (CMR) can clarify the pathophysiology of Q waves in dSSc patients. PATIENTS-METHODS: 105 dSSc, aged 48±2years, with atypical symptoms and normal routine assessment, were evaluated by ECG and CMR using a 1.5 T system. Biventricular function was assessed by steady-state free-precession sequence (SSFP). To identify fibrosis, late gadolinium enhanced areas (LGE) were evaluated 15min after injection of 0.2mmol/kg gadolinium-DTPA and expressed as % of LV mass. RESULTS: Q waves in V1-V5 (Group A), II, III, AVF (Group B) and I, AVL, II, III, AVF, V1-V5 (Group C) were found in 25/105, 8/105 and 5/105 dSSc, respectively. In 25 dSSc with Q in V1-V6, patchy intramyocardial LGE was detected in 24/25 and involved 8±2% of LV mass. LGE involved the intraventricular septum (IVS) in 11/24 and the lateral wall (LAT) in 5/24 dSSc. Only in 1/25 dSSc, an anterior, transmural LGE, due to LAD occlusion, was identified. In 8 dSSc with Q in II, III, AVF, patchy intramyocardial LGE was detected in the inferior wall and involved 5±2% of LV mass. In 5 dSSc with Q in V1-V5, II, III, AVF, patchy intramyocardial LGE was detected in anterior and inferolateral wall and involved 9±2% of LV mass. CONCLUSION: CMR unveiled that the pattern of myocardial fibrosis in dSSc with Q waves is due to the systemic disease and not to CAD.

Cardiovascular Magnetic Resonance Imaging clarifies cardiac pathophysiology in early, asymptomatic diffuse systemic sclerosis.

BACKGROUND: Myopericardial inflammation, perfusion's defects and fibrosis are major causes of cardiac disease in scleroderma (SSc). We hypothesized that using inflammation and stress perfusion-fibrosis cardiovascular magnetic resonance (CMR), we can identify the pathophysiology of heart disease in asymptomatic diffuse SSc. PATIENTS-METHODS: 46 recently diagnosed, asymptomatic patients with diffuse SSc had a CMR examination using a 1.5T system. ECG gated breath hold cine and short tau inversion recovery (STIR) T2 images were initially acquired. If T2 ratio<2 a stress perfusion-fibrosis protocol was applied. If T2>2 a myocarditis protocol including early (EGE) and late (LGE) gadolinium imaging was applied. SSc patients' results were compared with age and sex-matched controls and patients with coronary artery disease (CAD). RESULTS: In 2/46 SSc with T2 ratio>2, the myocarditis protocol was positive for acute myocardial inflammation, who developed clinical signs of acute myocarditis shortly after the CMR evaluation. In the rest 44/46 with T2 ratio<2 the stress perfusion-fibrosis CMR identified a significant reduction in Myocardial Perfusion Reserve Index (MPRI) compared with matched controls (0.6±0.4 vs 3.2±0.8, p<0.001), but not with CAD (0.6±0.4 vs 0.86±0.46, p=NS) and correlated only with the presence of digital ulcers (p<0.05). The scar was diffused and greater compared to controls, but did not differ from that assessed in CAD. Two years follow up, available in 11/44 SSc, showed further asymptomatic MPRI deterioration in all and diffuse subendocardial LGE in 8/11, without any change in LV, RV volumes and ejection fractions. CONCLUSION: CMR may reveal severe cardiac involvement in early, asymptomatic diffuse SSc with normal routine cardiac evaluation, presenting either as myocardial inflammation or as severe reduction of MPRI and diffuse fibrosis with further deterioration in the long term follow up.

Imaging Patterns of Cardiovascular Involvement in Mixed Connective Tissue Disease Evaluated by Cardiovascular Magnetic Resonance.

BACKGROUND: To clarify the imaging patterns of cardiovascular lesions in patients with mixed connective tissue disease (MCTD) and cardiovascular symptoms with or/ without abnormal routine non-invasive evaluation. PATIENTS-METHODS: Twenty-two MCTD patients (19F/3M), aged 38±4 yrs with cardiovascular symptoms were evaluated using a 1.5 T scanner. Of them, 8/22 had systemic lupus erythematosus (SLE), 5/22 rheumatoid arthritis (RA), 5/22 scleroderma (SSc) and 4/22 myositis (MY) overlap syndromes; 10/22 patients with MCTD presented with Raynaud phenomenon (RP) and all were positive for Anti-RNP antibodies. The cardiovascular magnetic resonance study (CMR) included evaluation of function, inflammation and fibrosis. Myocardial stress perfusion-fibrosis evaluation was performed only in MCTD patients with RP. RESULTS: A positive CMR study was identified in 4/8 with SLE, 1/5 with RA, 4/5 with SSc and in 1/4 with MY like MCTD. The CMR lesions were subendocardial or transmural LGE following the distribution of coronary arteries, intramyocardial LGE and diffuse subendocardial LGE in SLE-RA, MY and SSc like MCTD, respectively. Although no evidence of fibrosis was identified in patients with RP, adenosine stress myocardial perfusion revealed diffuse subendocardial perfusion defects. No correlation between disease duration and/or inflammatory indices and cardiac lesions was identified. CONCLUSION: CMR can reveal myocardial lesions in MCTD patients with cardiac symptoms including myocardial infarction, inflammation, diffuse subendocardial fibrosis and diffuse perfusion defects, necessitating further cardiac investigation and/or treatment.

Clinical queries addressed in patients with systemic autoimmune diseases. Can cardiovascular magnetic resonance give the final solution?

OBJECTIVES: To evaluate the potential of cardiovascular magnetic resonance (CMR) to answer queries, addressed in systemic autoimmune diseases (SAD). METHODS: Thirty-six patients aged 52±6 years, (range 27-71) with SAD and suspected cardiac disease underwent CMR by a 1.5 T, after routine evaluation, including clinical, ECG and echocardiographic examination. Steady-state, free precession cines, STIR T2-W and late gadolinium enhanced (LGE) images were evaluated. RESULTS: Abnormal findings were detected by: clinical evaluation in 14/36, ECG in 17/36, echocardiography in 11/36 and CMR in 30/36 SAD. Clinical, ECG and echocardiographic examination could not assess cardiac disease acuity and lesions'pathophysiology. In contrary, CMR identified cardiac lesions' etiology, acuity, need for catheterization and heart disease persistence, even if SAD was quiescent. CONCLUSION: Clinical, ECG and echocardiographic abnormalities may suggest, but not always interpret cardiac involvement in SAD. CMR can help to identify both etiology and acuity of cardiac lesions and guide further diagnostic and/or therapeutic approach in these patients.

Cardiac tissue characterization and the diagnostic value of cardiovascular magnetic resonance in systemic connective tissue diseases.

OBJECTIVE: Accurate diagnosis of cardiovascular involvement in connective tissue diseases (CTDs) remains challenging. We hypothesized that cardiovascular magnetic resonance (CMR) demonstrates cardiac lesions in symptomatic CTD patients with normal echocardiography. METHODS: CMR from 246 CTD patients with typical cardiac symptoms (TCS; n = 146, group A) or atypical cardiac symptoms (ATCS; n = 100, group B) was retrospectively evaluated. Group A included 9 patients with inflammatory myopathy (IM), 35 with sarcoidosis, 30 with systemic sclerosis (SSc), 14 with systemic lupus erythematosus (SLE), 10 with rheumatoid arthritis (RA), and 48 with small vessel vasculitis. Group B included 25 patients with RA, 20 with SLE, 20 with sarcoidosis, 15 with SSc, 10 with IM, and 10 with small vessel vasculitis. CMR was performed by 1.5T; left ventricular ejection fraction, T2 ratio (edema imaging), and late gadolinium enhancement (LGE; fibrosis imaging) were evaluated. Acute and chronic lesions were characterized as LGE positive plus T2 ratio >2 and T2 ratio ≤2, respectively. According to LGE, lesions were characterized as diffuse subendocardial, subepicardial, and subendocardial/transmural due to vasculitis, myocarditis, and myocardial infarction, respectively. A stress study by dobutamine echocardiography or stress, nuclear, or adenosine CMR was performed in CTD patients with negative rest CMR. RESULTS: Abnormal CMR was identified in 32% (27% chronic) and 15% (12% chronic) of patients with TCS and ATCS, respectively. Lesions due to vasculitis, myocarditis, and myocardial infarction were evident in 27.4%, 62.6%, and 9.6% of CTD patients, respectively. Stress studies in CTD patients with negative CMR revealed coronary artery disease in 20%. CONCLUSION: CMR in symptomatic CTD patients with normal echocardiography can assess disease acuity and identify vasculitis, myocarditis, and myocardial infarction.

Cardiovascular magnetic resonance imaging in asymptomatic patients with connective tissue disease and recent onset left bundle branch block.

BACKGROUND-AIM: Recent LBBB in connective tissue diseases (CTDs) is challenging, due to high incidence of underlying pathology that may remain undetected, due to limitations of imaging tests. We hypothesized that cardiovascular magnetic resonance (CMR) may be of diagnostic value in CTDs with recent LBBB and normal echocardiogram. PATIENTS-METHODS: 26 CTDs, aged 32 ± 7 yrs (19 F) and 26 controls without CTDs, aged 60 ± 4 yrs (10 F) with recent LBBB and normal echo were evaluated by CMR. The CTDs included 6 sarcoidosis (SRC), 4 systemic sclerosis (SSc), 6 systemic lupus erythematosus (SLE), 6 rheumatoid arthritis (RA) and 4 inflammatory myopathies (IM). CMR was performed by 1.5T. LVEF, T2 ratio (oedema imaging) and late gadolinium enhancement (LGE) (fibrosis imaging) were evaluated. Acute and chronic lesions were characterised by T2>2 and positive LGE and T2<2 and positive LGE, respectively. According to LGE, lesions were characterised as diffuse subendo-, subepicardial/intramural not following and subendocardial/transmural following the distribution of coronaries, indicative of vasculitis, myocarditis and myocardial infarction, respectively. RESULTS: CTDs were younger (p<0.001), with higher incidence of abnormal CMR (42.31 vs 30.77%, p=NS), including dilated cardiomyopathy (11.54%), diffuse subendocardial fibrosis (11.54%), myocardial infarction (7.69%) and acute myocarditis (11.54%) vs dilated cardiomyopathy (19.23%), myocardial infarction (7.69%) and acute myocarditis (3.85%), detected in non-CTDs. CONCLUSIONS: In CTDs with recent LBBB, CMR documented acute and chronic cardiac pathology, particularly myocarditis. CMR should be considered as an adjunct to conventional diagnostic workup in both patient groups, more so in CTDs.

Cardiac involvement in ANCA (+) and ANCA (-) Churg-Strauss syndrome evaluated by cardiovascular magnetic resonance.

INTRODUCTION: The cardiovascular magnetic resonance (CMR) pattern of Churg-Strauss syndrome (CSS) includes myopericarditis, diffuse subendocardial vasculitis or myocardial infarction with or without cardiac symptoms and is usually associated with lack of antineutrophil cytoplasmic antibodies (ANCA). AIM: To correlate the CMR pattern with ANCA in CSS, compare it with healthy controls and systemic lupus erythematosus (SLE) patients and re-evaluate 2 yrs after the first CMR. PATIENTS-METHODS: 28 consecutive CSS, aged 42±7 yrs, were referred for CMR and 2 yrs re-evaluation. The CMR included left ventricular ejection fraction (LVEF), T2-weighted (T2-W), early (EGE) and late gadolinium enhanced (LGE) imaging. Their results were compared with 28 systemic lupus erythematosus (SLE) under remission and 28 controls with normal myocardial perfusion, assessed by scintigraphy. RESULTS: CMR revealed acute cardiac lesions in all ANCA (-) CSS with active disease and acute cardiac symptoms and only in one asymptomatic ANCA (+) CSS, with active disease. Diffuse subendocardial fibrosis (DSF) or past myocarditis was identified in both ANCA(+) and ANCA (-) CSS, but with higher incidence and fibrosis amount in ANCA (-) CSS (p<0.05). In comparison to SLE, both ANCA (+) and ANCA (-) CSS had higher incidence of DSF, lower incidence of myocarditis and no evidence of myocardial infarction, due to coronary artery disease (p<0.05). In 2 yrs CMR follow up, 1/3 of CSS with DSF presented LV function deterioration and one died, although immunosuppressive treatment was given early after CSS diagnosis. CONCLUSIONS: Cardiac involvement either as DSF or myocarditis, can be detected in both ANCA (+) and ANCA (-) CSS, although more clinically overt in ANCA (-). DSF carries an ominous prognosis for LV function. CMR, due to its capability to detect disease severity, before cardiac dysfunction takes place, is an excellent tool for CSS risk stratification and treatment individualization.