Author + information
- Published online May 6, 2019.
- Luna Gargani, MD, PhD∗ (, )
- Giancarlo Todiere, MD, PhD,
- Serena Guiducci, MD, PhD,
- Cosimo Bruni, MD,
- Alessandro Pingitore, MD, PhD,
- Daniele De Marchi, BS,
- Silvia Bellando Randone, MD,
- Giovanni Donato Aquaro, MD,
- Laura Bazzichi, MD,
- Marta Mosca, MD, PhD,
- Massimo Lombardi, MD,
- Alessia Pepe, MD,
- Marco Matucci-Cerinic, MD, PhD and
- Eugenio Picano, MD, PhD
- ↵∗Institute of Clinical Physiology, National Research Council, Via Moruzzi, 1, 56124 Pisa, Italy
Cardiac involvement in systemic sclerosis (SSc) is frequent and significantly affects the prognosis. Myocardial fibrosis is the pathological hallmark and has been reported in >50% of necropsies (1). Given the low sensitivity of transthoracic echocardiography (TTE) in detecting myocardial fibrosis, late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is considered the noninvasive gold standard for imaging macroscopic myocardial fibrosis. Our aim was to evaluate the added value of LGE CMR to TTE in a large group of patients with SSc.
A total of 201 patients with SSc (90.5% women; 51 ± 14 years of age) without known SSc-related cardiac involvement were enrolled. All patients signed informed consent. All patients underwent comprehensive TTE with tissue Doppler imaging on the same day as 1.5-T LGE CMR with T1- and T2-weighted sequences. A standard 24-h Holter electrocardiogram (ECG) was recorded when clinically indicated; ventricular arrhythmias were defined by Lown classification grade ≥2.
T2-weighted CMR showed myocardial edema in 5 patients (2.5%), all without clinical or biochemical features suggestive of myocarditis. Positive LGE (with negative T2-weighted images) was detected in 56 (27.9%) patients, with a nonischemic pattern in all but 3 patients. Mean LGE at quantitative analysis was 2.8 ± 1.3 g. The main abnormalities assessed by CMR, with their prevalence and localization, are reported in Figure 1. The presence of exertional dyspnea was similarly distributed between patients with and without LGE (50% vs. 41.4%; p = 0.43). TTE did not show significant abnormalities in 74% of patients with myocardial fibrosis. No TTE parameter was able to predict LGE presence at CMR.
A correlation was found between LGE presence and Holter ECG ventricular arrhythmias (chi-square test = 9.5; p < 0.01). Patients with ventricular arrhythmias also showed a greater amount of LGE at quantitative analysis (2.6 ± 2.1 g vs. 1.2 ± 1.5 g; p < 0.01). No other clinical characteristic was able to discriminate between patients with presence and/or amount of LGE.
To the best of our knowledge, this is the largest SSc group evaluated for the complementary role of CMR and echocardiography in detecting early cardiac involvement. We found that LGE is frequent in patients with SSc, irrespective of symptoms, and is linked to ventricular arrhythmias at Holter ECG. This finding may have relevant clinical implications, underlining the role of fibrosis as a potential trigger for arrhythmias. The high percentage of patients with LGE among those who have a positive Holter ECG suggests a role for Holter ECG as a possible gatekeeper for CMR. Although recommendations support CMR to refine the clinical suspicion of myocardial involvement when TTE is inconclusive (2), the lack of predictive TTE abnormalities in our group of patients makes the selection of patients who may benefit of CMR challenging when this selection is based only on TTE. About 30% of our patients showed LGE at right ventricular insertion sites. It may be argued that LGE at this localization can be related to expanded extracellular space, rather than to replacement fibrosis, possibly linked to pulmonary parenchymal and/or vascular involvement, although these differences were not significant in our group of patients. Its clinical value will remain uncertain until it can be clearly linked to prognostic data (3).
A small proportion of patients, although asymptomatic, had CMR signs of myocardial edema that was reversible after steroid therapy. Subclinical myocarditis is frequent in SSc (4), but it may be argued whether it is worth treating. In our experience, prompt pharmacological therapy led to complete resolution of CMR signs of myocardial edema (5), but as with LGE, only prognostic data can fully clarify this aspect.
The lack of T1 mapping analysis is a limitation of the present study. As soon as the technique was available in our laboratory, we evaluated T1 mapping in a subgroup of this group of patients; it showed that myocardial extracellular volume fraction was significantly increased in patients with SSc with normal biventricular volumes and systolic function, compared with control subjects (6).
In conclusion, CMR can detect frequent subclinical SSc-related cardiac involvement, which is linked to ventricular arrhythmias. Prognostic data are needed to clarify the long-term clinical implications of these imaging abnormalities.
Please note: Dr. Gargani has received speaker fees from GE Healthcare and GlaxoSmithKline. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2019 American College of Cardiology Foundation
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