Cardiac resynchronization therapy in adults with structural congenital heart disease and chronic heart failure.

AIMS: Evidence for CRT in adults with congenital heart disease (ACHD) and chronic heart failure is limited, with recommendations for its use extrapolated from the population with structurally normal hearts. This retrospective observational study investigates the efficacy of CRT in this heterogenous group, discussing factors predicting response to CRT. METHODS: Twenty-seven patients with structural ACHD who underwent CRT insertion or upgrade at a tertiary center in the United Kingdom were retrospectively studied. The primary outcome measure was clinical response to CRT, defined as improvement of NYHA class and/or improvement in systemic ventricular ejection fraction by one category. Secondary outcomes included change in QRS duration and adverse events. RESULTS: Thirty-seven percent of patients had a systemic right ventricle (sRV). RBBB was the commonest baseline QRS morphology (40.7%) despite this being an unfavorable characteristic for CRT. Overall, positive response to CRT was demonstrated in 18 patients (66.7%). NYHA class improved in 55.5% following CRT (p = .001) and 40.7% showed improvement in systemic ventricular ejection fraction (p = .118). There were no baseline characteristics that predicted response to CRT, and electrocardiographic measures such as QRS shortening post-CRT was not associated with positive response. Good response rates (60.0%) were demonstrated in those with sRV. CONCLUSION: CRT is efficacious in structural ACHD including in those who do not meet conventional criteria. Extrapolation of recommendations from adults with structurally normal hearts may be inappropriate. Future research should focus on improving patient selection for CRT, for example using techniques to better quantify mechanical dysynchrony and intra-procedural electrical activation mapping in these complex patients.

The use of Macitentan in Fontan circulation: a case report.

BACKGROUND: The Fontan circulation, a result of a palliative procedure in patients with single systemic ventricles, is defined by chronically elevated pulmonary vascular resistance. When traditional heart failure therapies fail, pharmacological agents that reduce pulmonary artery pressures may be used. These include endothelial-receptor antagonists, prostanoids and phosphodiesterase type 5 inhibitors. We report the first use of macitentan, an endothelin-receptor antagonist, in a patient with a Fontan circulation. CASE PRESENTATION: We describe the case of a 50 year old female with tricuspid atresia and transposition of the great arteries. Following complex surgery as a child, she subsequently underwent a fenestrated modified atrial pulmonary Fontan operation which was later converted to a total cavopulmonary anastomosis Fontan circulation. Due to failure of various medications to relieve her worsening symptoms, she was commenced on macitentan in April 2016. Few months later, she demonstrated a significant symptomatic improvement and associated increase in her incremental shuttle walking test distance. CONCLUSIONS: Macitentan has slower receptor dissociation kinetics compared to other endothelin-receptor antagonists, leading to enhanced pharmacological activity with promising effects in patients with pulmonary arterial hypertension. The patient we report has shown considerable improvement in exercise capacity following introduction of this medication and thus we suggest further randomised trials to establish the role of different endothelin-receptor antagonists in the management of the Fontan circulation.

Long-term outcome following pregnancy in women with a systemic right ventricle: is the deterioration due to pregnancy or a consequence of time?

INTRODUCTION: The right ventricle (RV) supports the systemic circulation in patients who have had an intraatrial repair of transposition of the great arteries or have congenitally corrected transposition. There is concern about the ability of a systemic RV to support the additional volume load of pregnancy, and previous studies have reported deterioration in RV function following pregnancy. However, conditions with a systemic RV are also associated with progressive RV dysfunction over time. To date, no study has examined whether the deterioration associated with pregnancy is due to the physiological changes of pregnancy itself, or is part of the known deterioration that occurs with time in these patients. METHODS: Women who had undergone pregnancy under the care of the Adult Congenital Heart Disease Unit at the Queen Elizabeth Hospital were retrospectively identified and matched to separate male and nulliparous female controls. Functional status (New York Health Association [NYHA]), RV function, and systemic atrioventricular valve regurgitation were recorded for each group at baseline, postpregnancy (or at 1 year for control groups) and at latest follow-up. RESULTS: Eighteen women had 31 pregnancies (range 1-4) resulting in 32 live births. There were no maternal but one neonatal death. At baseline, there was no significant difference in NYHA class or RV function between pregnancy and control groups. In postpregnancy, there was a significant deterioration in the pregnant group alone for both NYHA class (P = 0.004) and RV function (P = 0.02). At latest follow-up, there was a significant deterioration in RV function in all three groups. There was still a reduction from baseline in NYHA of women who had undergone pregnancy (P = 0.014), which again was not seen in the controls groups. CONCLUSION: This study suggests that pregnancy is associated with a premature deterioration in RV function in women with a systemic RV. These women are also more symptomatic, with a greater reduction in functional class compared with patients with a systemic RV who do not undergo pregnancy. This study will allow this cohort of women to be more accurately counseled as to the potential long-term risks of pregnancy.

End-of-life care in adults with congenital heart disease: now is the time to act.

PURPOSE OF REVIEW: There are increasing numbers of adults with congenital heart disease (CHD) and these patients remain at long-term risk of complications and premature death. This review focuses on the changing picture of adult CHD with more complex patients surviving, the challenges of balancing life-prolonging intervention, the barriers to discussing the end-of-life (EOL) issues and draws on the experience of other specialities in managing young patients. RECENT FINDINGS: The prevalence of adults with the most severe forms of CHD has increased, especially those with a Fontan circulation. The eventual decline is inevitable with limited treatment options. There should be a parallel palliative care approach in patients who are being considered for high-risk, life-prolonging interventions. Oncologists caring for the young patients with cancer and cystic fibrosis specialists have demonstrated the unique needs of young patients with chronic diseases that may be applicable to adult CHD patients and help with their EOL planning. SUMMARY: These patients require an early and proactive approach to EOL discussions, and the unique needs of young patients should be recognized. Further research is needed to develop local and national guidelines for the palliative care approach in these patients.

The safety and effects of bosentan in patients with a Fontan circulation.

OBJECTIVE: Adult patients with a Fontan circulation tend to have diminished exercise capacity. The principal objective of this study was to investigate the safety of the endothelin receptor antagonist bosentan in Fontan patients, and, secondarily, to assess effects on cardiovascular performance, New York Heart Association functional classification (NYHA FC), and ventricular function. DESIGN: A 6-month prospective, single-center, pilot, safety study of bosentan in Fontan patients. Setting. Adult Congenital Heart Disease referral center. PATIENTS: All patients ≥18 years old with a Fontan circulation and in NYHA FC ≥II were invited to enroll. Interventions. Patients started on 62.5 mg bid of bosentan, uptitrating to 125 mg bid after 2 weeks. OUTCOME MEASURES: Safety was assessed by the incidence of anticipated and unanticipated adverse events during the 6-month study period; specifically those relating to hepatic, renal, or hematological dysfunction as measured by monthly blood tests. Other outcome measures included cardiopulmonary exercise test, 6-minute walk distance test, Borg dyspnea index, NYHA FC, and ventricular function parameters using transthoracic echocardiography. RESULTS: Of the eight patients enrolled, six completed the study. Two patients withdrew from the study (one for non-trial related reasons, one due to adverse events). No clinically significant adverse events relating to bosentan therapy occurred during this study and, in particular, no significant abnormalities in hepatic function tests were observed. Three patients reported transient adverse events. Improvements in NYHA FC and systolic ventricular function were observed after 6 months of bosentan treatment. CONCLUSIONS: The small number of patients with a Fontan circulation in our study was able to tolerate bosentan for 6 months. The safety and tolerability of bosentan in a larger patient population remains unknown. The results presented here justify further investigation in larger studies.