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.

Partial anomalous pulmonary venous drainage in patients presenting with suspected pulmonary hypertension: A series of 90 patients from the ASPIRE registry.

BACKGROUND AND OBJECTIVE: There are limited data regarding patients with PAPVD with suspected and diagnosed PH. METHODS: Patients with PAPVD presenting to a large PH referral centre during 2007-2017 were identified from the ASPIRE registry. RESULTS: Ninety patients with PAPVD were identified; this was newly diagnosed at our unit in 71 patients (78%), despite 69% of these having previously undergone CT. Sixty-seven percent had a single right superior and 23% a single left superior anomalous vein. Patients with an SV-ASD had a significantly larger RV area, pulmonary artery and L-R shunt and a higher % predicted DLCO (all P < 0.05). Sixty-five patients were diagnosed with PH (defined as mPAP ≥ 25 mm Hg), which was post-capillary in 24 (37%). No additional causes of PH were identified in 28 patients; 17 of these (26% of those patients with PH) had a PVR > 3 WU. Seven of these patients had isolated PAPVD, five of whom (8% of those patients with PH) had anomalous drainage of a single pulmonary vein. CONCLUSION: Undiagnosed PAPVD with or without ASD may be present in patients with suspected PH; cross-sectional imaging should therefore be specifically assessed whenever this diagnosis is considered. Radiological and physiological markers of L-R shunt are higher in patients with an associated SV-ASD. Although many patients with PAPVD and PH may have other potential causes of PH, a proportion of patients diagnosed with PAH have isolated PAPVD in the absence of other causative conditions.

Supervised pulmonary hypertension exercise rehabilitation (SPHERe): study protocol for a multi-centre randomised controlled trial.

BACKGROUND: Supervised cardio-pulmonary rehabilitation may be safe and beneficial for people with pulmonary hypertension (PH) in groups 1 (pulmonary arterial hypertension) and 4 (chronic thromboembolic disease), particularly as a hospital in-patient. It has not been tested in the most common PH groups; 2 (left heart disease), 3 (lung disease), or 5 (other disorders). Further it has not been evaluated in the UK National Health Service (NHS) out-patient setting, or with long-term follow-up. The aim of this randomised controlled trial (RCT) is to test the clinical and cost-effectiveness of a supervised exercise rehabilitation intervention with psychosocial support compared to best practice usual care for people with PH in the community/outpatient setting. METHODS: This multi-centre, pragmatic, two-arm RCT with embedded process evaluation aims to recruit 352 clinically stable adults with PH (groups 1-5) and WHO functional class II-IV. Participants will be randomised to either the Supervised Pulmonary Hypertension Exercise Rehabilitation (SPHERe) intervention or control. The SPHERe intervention consists of 1) individual assessment and familiarisation sessions; 2) 8-week, twice-weekly, supervised out-patient exercise training; 3) psychosocial/motivational support and education; 4) guided home exercise plan. The control intervention consists of best practice usual care with a single one-to-one practitioner appointment, and general advice on physical activity. Outcomes will be measured at baseline, 4 months (post-intervention) and 12 months by researchers blinded to treatment allocation. The primary outcome is the incremental shuttle walk test at 4 months. Secondary outcomes include health-related quality of life (HRQoL), time to clinical worsening and health and social care use. A purposive sample of participants (n = 20 intervention and n = 20 control) and practitioners (n = 20) will be interviewed to explore experiences of the trial, outcomes and interventions. DISCUSSION: The SPHERe study is the first multi-centre clinical RCT to assess the clinical and cost effectiveness of a supervised exercise rehabilitation intervention compared to usual care, delivered in the UK NHS, for people in all PH groups. Results will inform clinicians and commissioners as to whether or not supervised exercise rehabilitation is effective and should be routinely provided for people with PH. TRIAL REGISTRATION: ISRCTN no. 10608766, prospectively registered on 18th March 2019.

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.

Improvement in cardiac energetics by perhexiline in heart failure due to dilated cardiomyopathy.

OBJECTIVES: The aim of this study was to determine whether short-term treatment with perhexiline improves cardiac energetics, left ventricular function, and symptoms of heart failure by altering cardiac substrate utilization. BACKGROUND: Perhexiline improves exercise capacity and left ventricular ejection fraction (LVEF) in patients with heart failure (HF). (31)P cardiac magnetic resonance spectroscopy can be used to quantify the myocardial phosphocreatine/adenosine triphosphate ratio. Because improvement of HF syndrome can improve cardiac energetics secondarily, we investigated the effects of short-term perhexiline therapy. METHODS: Patients with systolic HF of nonischemic etiology (n = 50, 62 ± 1.8 years of age, New York Heart Association functional class II to IV, LVEF: 27.0 ± 1.44%) were randomized to receive perhexiline 200 mg or placebo for 1 month in a double-blind fashion. Clinical assessment, echocardiography, and (31)P cardiac magnetic resonance spectroscopy were performed at baseline and after 1 month. A substudy of 22 patients also underwent cross-heart blood sampling at completion of the study to quantify metabolite utilization. RESULTS: Perhexiline therapy was associated with a 30% increase in the phosphocreatine/adenosine triphosphate ratio (from 1.16 ± 0.39 to 1.51 ± 0.51; p < 0.001) versus a 3% decrease with placebo (from 1.36 ± 0.31 to 1.34 ± 0.31; p = 0.37). Perhexiline therapy also led to an improvement in New York Heart Association functional class compared with placebo (p = 0.036). Short-term perhexiline therapy did not change LVEF. Cross-heart measures of cardiac substrate uptake and respiratory exchange ratio (which reflects the ratio of substrates used) did not differ between patients who received perhexiline versus placebo. CONCLUSIONS: Perhexiline improves cardiac energetics and symptom status with no evidence of altered cardiac substrate utilization. No change in LVEF is seen at this early stage. (Metabolic Manipulation in Chronic Heart Failure; NCT00841139).

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.

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.

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.