Cardiac manifestations in systemic sclerosis

Table 1 Features of myocardial involvement in systemic sclerosis distinct from coronary atherosclerotic disease

Characteristic features
Microvascular ischemia
Patchy fibrosis, unrelated to coronary epicardial artery distribution
Involvement of immediate subendocardium, which is spared in atherosclerosis
Contraction band necrosis
Concentric intimal hypertrophy associated with fibrinoid necrosis of intramural coronary arteries
Hemosiderin deposits are not typically seen; they are evident in the atherosclerotic process

Table 2 Therapies for systemic sclerosis-related pulmonary arterial hypertension[64-82]

Therapeutic approach	Dosage/comments
Prostanoids
Epoprostenol: a prostacyclin with a very short half-life of 6 min; unstable at pH values below 10.5, requires intravenous administration[54,68]	Starting dose is 1-2 ng/kg per minute, gradually increased up to 25-40 ng/kg per minute
Treprostinil: an epoprostenol analogue with a half-life of 4.5 h, given as a continuous subcutaneous or intravenous infusion in patients with PAH from functional class II, III and IV[54,69]	10-20 ng/kg per minute
Iloprost: a chemically stable prostacyclin analogue with a longer half-life (20–25 min), given as a continuous intravenous infusion for 6-8 h[70]	0.5-3.0 ng/kg per minute
Beraprost: the first oral prostacyclin analogue with vasodilative and antiplatelet action and a half-life of approximately 1 h, indicated in primary and secondary PAH[72,73]	20 μg qid, may be increased by 20 μg/wk. The maximum allowed dose was 120 μg qid with a mean of 80 μg qid
Prostaglandins for inhalation
Iloprost: inhalation has a pulmonary vasodilative potency similar to prostacyclin with longer effects (30-90 vs 15 min); effective in patients with severe PAH functional class III and IV[71]	2.5 or 5.0 mg six or nine times/d; median inhaled dose, 30 μg/d
Endothelin receptor antagonists
Bosentan: the first drug from this group that was approved for treatment of PAH associated with systemic rheumatic diseases in the United States, Canada, Switzerland and European Union; indicated for PAH functional classes II, III and IV[74,75]	62.5 mg bid for 4 wk before titration up to 125-250 mg bid
Sitaxsentan: highly selective endothelin receptor antagonist with a long duration of action; high specificity for type A over type B receptors (6500:1) leads to blockade of the vasoconstrictory effect of endothelin-1 and maintainence of the vasodilative and clearance function of type B receptors[76]	50-100 mg/d
Ambrisentan: antagonist selective for type A over type B endothelin receptors (4000:1)[77]	2.5-10 mg
PDE inhibitors
(PDE degrades cGMP, which mediates the effect of nitric oxide-a potent vasodilator and an inhibitor of platelet activation and vascular smooth muscle)
Sildenafil: a specific inhibitor of the PDE-5 isoform present in large amounts in the lung[78]	20 mg 3 tid
Vardenafil: a PDE-5 inhibitor[80]	20 mg 3 tid
Tadalafil: a specific inhibitor of PDE-5 with a longer half-life (17.5 vs 3.8 h for sildenafil)[79]	20 mg 3 tid
Combination therapy
(oral with inhaled and intravenous drugs)
Sildenafil with intravenous epoprostenol Sildenafil and bosentan[81]
Others
Sodium consumption needs to be restricted to 2400 mg/d in patients with right ventricular failure; digoxin and diuretics when indicated	Saturation < 90% at rest or with exercise; Titration to an international normalized ratio of 1.5-2.5
Surgical options: atrial septostomy, single and double lung transplantation and combined heart and lung transplantation are ultimate therapeutic options in patients with end-stage disease[54]
Routine immunization against influenza and pneumococcal pneumonia
Oxygen therapy
Anticoagulation therapy: (warfarin) in advanced stages with continuous intravenous therapy and in the absence of contraindications
Although inflammation plays a significant role in the development and the progression of PAH, immunosuppression is not a common treatment, as systemic sclerosis-PAH is usually quite refractory to immunosuppressive drugs[82]. However, immunosuppressive treatment has led to improvements in some cases of PAH in other connective tissue diseases (e.g., systemic lupus erythematosus, primary Sjögren syndrome)

PDE: Phosphodiesterase; PAH: Pulmonary arterial hypertension.

Table 3 Criteria for definition of hypertensive scleroderma renal crisis

In the presence of limited or diffuse cutaneous scleroderma renal crisis:

A new onset of blood pressure > 150/85 mmHg obtained at least twice over a 24 h period. This blood pressure is defined as significant hypertension by the New York Heart Association

A documented decrease in renal function as defined by a decrement of at least 30% in the calculated glomerular filtration rate. When possible, initial results should be confirmed by a repeat serum creatinine concentration and recalculation of the glomerular filtration rate

To corroborate further the occurrence of acute renal crisis, it would be desirable to have any of the following (if available):

Microangiopathic hemolytic anemia on blood smear

Retinopathy typical of acute hypertensive crisis

New onset of urinary red blood cells (excluding other causes)

Flash pulmonary edema

Oliguria or anuria

Renal biopsy showing characteristic changes

Renal biopsy showing an alternative cause excludes the case from classification as scleroderma renal crisis