Iron deficiency in pulmonary arterial hypertension: prevalence and potential usefulness of oral supplementation.

BACKGROUND: The aim of this study was to evaluate the prevalence of iron depletion in a prevalent population of patients with pulmonary arterial hypertension (PAH) and to gain preliminary insights on the possibility of its treatment with oral drugs. METHODS: Iron status was determined in 31 consecutive prevalent idiopathic patients with PAH. Iron depletion was defined as serum iron <10 mmol/L and decreased transferrin saturation irrespective of the coexistence of anaemia. Patients underwent laboratory examinations, 6-min walking test and echocardiography in the same day. A subgroup of iron depleted patients received one oral capsule/day containing 30 mg of pyrophosphate sucrosomial iron for 16 weeks. After this period all patients were re-evaluated. RESULTS: Iron depletion was observed in 22 patients (71%), of whom 6 were also anaemic and 16 were not anaemic. Iron depletion was associated with higher systolic pulmonary artery pressure (60 [50-90] vs. 45 [40-50] mmHg, p = .007), greater prevalence of moderate to severe tricuspid regurgitation (36% vs. 0%, p = .039), lower tricuspid annular plane systolic excursion (23 [21-24] vs. 19 [18-20] mm; p = .025]) and higher left ventricular eccentricity index (1.35 vs. 1, p = .042). After 16 weeks of treatment, 6-min walking distance significantly improved (500 [390-500] vs. 530 [410-550] metres; p = .043). CONCLUSIONS: Iron deficiency is highly prevalent in patients with PAH and is associated with worse clinical conditions. Treatment with oral sucrosomial iron is a therapeutic option which should be further investigated in future trials.

Dobutamine stress echocardiography in pulmonary arterial hypertension.

BACKGROUND: There is a growing interest in exploring the concept of right ventricular functional reserve in patients with pulmonary arterial hypertension. However, it is still unclear how it should be assessed. Aim of the study was to investigate the determinants of the changes in cardiac output and in pulmonary pressure during dobutamine stress echocardiography in pulmonary arterial hypertension. METHODS: Low-dose dobutamine stress echocardiography was performed in 55 patients and 28 controls. Tricuspid annular plane systolic excursion, its ratio to systolic pulmonary artery pressure, right ventricular area change, degree of tricuspid regurgitation, right ventricular end-systolic pressure-area ratio, cardiac output were assessed at rest and at peak stress. RESULTS: According to the stress induced increase in cardiac output, patients were classified into 2 groups: above/equal to the median of 2.8 L/min (high cardiac output) or below the median (low cardiac output). High cardiac output patients were characterized by a greater increase in heart rate (+45.1 ±â€¯17.5 vs +21.3 ±â€¯17.7 bpm), a greater improvement in tricuspid annular plane systolic excursion (+4.2 ±â€¯3.3 vs +1.9 ±â€¯2.6 mm, P = 0.005) and a decrease in tricuspid regurgitation (P = 0.010) as compared to low cardiac output patients. Changes in pulmonary pressure were not associated with changes in indicators of right ventricular function but only with changes in heart rate. CONCLUSIONS: The increase in cardiac output during dobutamine is associated with an improvement in longitudinal right ventricular function, a decrease in tricuspid regurgitation and an increase in heart rate. Changes in pulmonary pressure only reflect the changes in heart rate.

Propranolol prevents life-threatening arrhythmias in LQT3 transgenic mice: implications for the clinical management of LQT3 patients.

BACKGROUND: The efficacy of beta-blockers for treatment of patients with long QT syndrome type 3 (LQT3) has been repeatedly questioned, and it has been suggested that they might be detrimental for this genetic subgroup of patients with long QT syndrome (LQTS). The disquieting consequence has been that cardiologists confronted with LQT3 patients often do not even attempt pharmacologic therapy and implant cardioverter-defibrillators as first-choice treatment. However, the most recent clinical data indicate high efficacy of beta-blocker therapy in LQT3 patients. OBJECTIVE: The purpose of this study was to test the antiarrhythmic efficacy of beta-blockers in an established experimental model for LQT3. METHODS: After phenotypic validation of 65 ∆KPQ-SCN5A knock-in transgenic (TG) mice compared to 32 wild-type (WT) mice, we tested the effect of the arrhythmogenic cholinergic muscarinic agonist carbachol in 19 WT and 39 TG anesthetized mice, with and without pretreatment with propranolol given intraperitoneally. RESULTS: At the same heart rates, TG mice had a markedly longer QT interval than WT mice. Whereas carbachol had minor arrhythmic effects in the WT mice, it produced ventricular tachycardia (VT) and ventricular fibrillation (VF) in 55% of 20 TG mice. By contrast, in none of 19 TG mice pretreated with propranolol did VT/VF occur after carbachol injection. CONCLUSION: These experimental data indicate that, contrary to previous reports, beta-blockade effectively prevents VT/VF in a validated LQT3 model. Together with the most recent clinical data, these findings indicate that there is no reason for not initiating protective therapy with beta-blockers in LQT3 patients.