A pilot study on the effects of carvedilol on right ventricular remodelling and exercise tolerance in patients with systemic right ventricle

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Abstract

Background

Patients with atrial repair for transposition of the great arteries and patients with congenitally corrected transposition have a right ventricle (RV) in the systemic position and they may develop RV dysfunction and exercise intolerance with advancing age. No data is available on the effect of carvedilol in patients with dysfunctional systemic RV.

Methods

We studied with cardiovascular magnetic resonance (CMR), cardiopulmonary exercise testing, and standard 12-leads electrocardiogram, 8 adults (median age 26 years, range 18–31) with chronic stable heart failure and systemic RV dysfunction (6 patients with atrial repair and 2 patients with congenitally corrected transposition). Assessment was done before and after 12 months of carvedilol administration. The initial dose was 3.125 mg twice daily, and the target dose was 25 mg twice a day.

Results

Carvedilol administration was safe and the target dose was achieved in 5/8 (62%) patients. Right ventricular end-diastolic (119 ± 31 vs. 112 ± 28 ml/m2, p = 0.01) and end-systolic volumes decreased (79 ± 17 vs. 65 ± 14 ml/m2, p = 0.006), and RV ejection fraction improved (34 ± 6 vs. 42 ± 7%, p = 0.004). Left ventricular ejection fraction increased (44 ± 8 vs. 49 ± 9%, p = 0.01), suggesting a positive biventricular remodelling. Peak oxygen uptake did not change with carvedilol (26.8 ± 5.3 vs. 27.3 ± 5.7 ml O2/Kg/min, p = 0.58), whereas exercise duration increased (13.4 ± 2.6 vs. 17.3 ± 3.1 min, p = 0.008).

Conclusions

In this small cohort, carvedilol administration was safe and it was associated with positive RV remodelling as well as improved exercise duration.

Introduction

Patients who have undergone atrial repair for transposition of the great arteries, and patients with congenitally correct transposition of the great arteries both have a systemic ventricle of right ventricular (RV) morphology. The systemic RV is exposed to long-term systemic pressure workload, and progressive RV dilation and dysfunction, decreased exercise tolerance, arrhythmias, and sudden death are increasingly seen with advancing age [1], [2], [3], [4], [5], [6], [7], [8].

Myocardial ischemia has been reported in this setting and is associated with progressive RV dysfunction [9], [10]. The use of beta-blockers in patients with either ischemic or non-ischemic cardiomyopathies has been associated with an improvement in cardiac function and long-term survival [11], [12], [13], [14], [15], but no data is available for patients with a systemic RV. The purpose of the present study is to investigate, using cardiovascular magnetic resonance (CMR) and cardiopulmonary exercise testing (CPX), the effects of carvedilol on RV remodelling and exercise tolerance in patients with systemic RV.

Section snippets

Patients

Between June 2003 and February 2004 18 patients with a systemic RV were seen at our outpatient clinic. Twelve patients had RV dysfunction [16] and were considered for carvedilol administration. Two patients were excluded from the study since they had a permanent pacemaker, whereas 2 patients refused to undergo CMR. The study cohort therefore consisted of 8 patients with a dysfunctional RV, with a median age of 26 years (range 18–31). Patients were studied with CMR and CPX both before (1 to

Statistical analysis

Data is expressed as mean ± SD or median (range) according to distribution. Right and left ventricular volumes and mass were indexed to body surface area before entering statistical analysis. Wilcoxon matched pairs test or paired t test was used to compare clinical, ECG, CMR, and CPX variables before vs. after carvedilol administration, when appropriate. In the first 4 patients, RV mass, volumes, and ejection fraction were compared between the two observers. For each variable, the standard

Results

No major adverse event occurred during the period of carvedilol up-titration or during follow-up. The final dose of 50 mg/day was reached in 5 patients. Two patients did not tolerate the up-titration from 25 mg/day to 50 mg/day because of profound fatigue associated with systolic blood pressure < 90 mm Hg. One patient did not tolerate the up-titration from 12.5 mg/day to 25 mg/day because he developed symptomatic sinus bradycardia (fatigue associated with a heart rate of 50 bpm and PR interval > 

Discussion

Progressive RV dysfunction and exercise intolerance are common in the long-term follow-up of patients with a systemic RV and are associated with an adverse outcome [1], [3], [5], [6], [9]. The results of this pilot study indicate that administration of carvedilol in this setting is reasonably safe and is associated with RV reverse remodelling, and improvement of RV function and exercise tolerance.

Like the adaptive up-regulation of the renin–angiotensin–aldosterone system, the failing heart

Conclusions

In this pilot study, carvedilol administration appeared safe and was associated with positive RV remodelling as well as improved exercise duration.

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