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Blunted coronary flow reserve in systemic sclerosis: a sign of cardiac involvement in asymptomatic patients
  1. A Sulli1,
  2. M Ghio3,
  3. G P Bezante2,
  4. L Deferrari2,
  5. C Craviotto1,
  6. V Sebastiani2,
  7. M Setti3,
  8. G Filaci3,
  9. F Puppo3,
  10. A Barsotti2,
  11. M Cutolo1,
  12. F Indiveri3
  1. 1Division of Rheumatology, Department of Internal Medicine, University of Genova, Genova, Italy
  2. 2Division of Cardiology, Department of Internal Medicine, University of Genova, Genova, Italy
  3. 3Division of Immunology and Internal Medicine, Department of Internal Medicine, University of Genova, Genova, Italy
  1. Correspondence to:
    Dr A Sulli
    Research Laboratory and Division of Rheumatology, Department of Internal Medicine, University of Genova, Viale Benedetto XV No 6, 16132 Genova, Italy; albertosulliunige.it

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Cardiac disease is often present in systemic sclerosis (SSc), even if rarely of clinical significance.1–3 Therefore, we investigated the coronary flow reserve (CFR), by transthoracic contrast enhanced second harmonic Doppler echocardiography, a non-invasive method that might detect early heart dysfunction in patients with SSc even in the absence of clinical signs or symptoms.

Twenty nine consecutive patients (2 male, 27 female, mean (SD) age 55 (14) years) affected by SSc,4,5 not complaining of signs or symptoms of cardiovascular involvement, were recruited. No further serious disease other than SSc was present. Eleven healthy subjects matched for age and sex (mean (SD) age 53 (5) years) were also evaluated as controls. Echocardiography was performed with an ultrasound unit using a broadband transducer with second harmonic capability in both B mode and Doppler modality. Levovist was used as the ultrasound contrast agent.6,7 The CFR, expressed as the ratio between hyperaemic (peak adenosine infusion) and resting, both peak, diastolic velocity (PdvCFR) and velocity time integral (VtiCFR), was non-invasively assessed in the distal left anterior descending coronary. Peripheral microangiopathy was assessed by nailfold videocapillaroscopy (NVC), as previously reported.8

All patients were found in sinus rhythm, without any significant ECG alteration. All ECG parameters were normal.

The study showed a reduced CFR in 14/29 patients with SSc, when compared with the normal range of healthy subjects matched for age and sex (CFR >2.00).7 In particular, both PdvCFR and VtiCFR, were strongly reduced in patients with SSc (mean (SD) 1.93 (0.56) and 1.81 (0.56), respectively) in comparison with controls (3.11 (0.72) and 2.83 (0.51), respectively) (p<0.0001). Furthermore, both PdvCFR and VtiCFR were significantly lower in patients with diffuse SSc (1.74 (0.46) and 1.59 (0.38), respectively) than in patients with limited SSc (2.39 (0.52) and 2.35 (0.38), respectively) (p<0.004 and p<0.001, respectively) (fig 1).

Nineteen patients (mean (SD) age 52 (13) years) and 10 patients (mean (SD) age 63 (12) years) had diffuse SSc (dSSc) and limited SSc (lSSc), respectively; the patients with dSSc were younger than those with lSSc (p<0.04).

Glucose serum levels were normal in all patients with SSc. No statistically significant correlation was found between CFR and history of smoking and cholesterol or triglyceride serum levels. Moreover, no statistically significant correlation was found between CFR and blood pressure values.

No statistically significant correlation was found between CFR and the age of the patients, duration of SSc, or the presence of antinuclear antibodies, anticentromere antibodies, and Scl-70.

No statistically significant CFR difference was found between patients with different degrees of peripheral microangiopathy (“early”, “active”, and “late” scleroderma pattern, as assessed by NVC).

Therefore, this study showed that patients with SSc may have clinically asymptomatic heart function impairment. In particular, the CFR values detected were significantly lower in patients with dSSc than in patients with lSSc. Patients with dSSc were younger than those with lSSc, indicating that the age of the patients is not important in the development of scleroderma heart disease. Patients with lSSc often develop clinical manifestations that are different or less severe than those of patients with dSSc, and the lower CFR found in patients with dSSc seems to support to this observation. Therefore, the present results confirm previous studies showing that patients with dSSc often have cardiac disease.9,10

In conclusion, CFR evaluation is an efficient, non-invasive, and reliable tool for assessing early cardiac disease in SSc. A reduced CFR value should be considered an indirect sign of SSc heart involvement, even if its clinical and prognostic significance needs to be further clarified.

Figure 1

CFR in patients with SSc and controls (Cntr), assessed by transthoracic contrast enhanced second harmonic Doppler and expressed as the ratio between hyperaemic and resting, both peak, diastolic velocity (PdvCFR) (A) and velocity time integral (VtiCFR) (B). dSSc, patients with diffuse SSc; lSSc, patients with limited SSc.

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