Sarah Bowater

Improvement in Cardiac Energetics by Perhexiline in Heart Failure Due to Dilated Cardiomyopathy

OBJECTIVESnThe 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.nnnBACKGROUNDnPerhexiline 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.nnnMETHODSnPatients with systolic HF of nonischemic etiology (nxa0= 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.nnnRESULTSnPerhexiline therapy was associated with a 30% increase in the phosphocreatine/adenosine triphosphate ratio (from 1.16 ± 0.39 to 1.51 ± 0.51; pxa0< 0.001) versus a 3% decrease with placebo (from 1.36 ± 0.31 to 1.34 ± 0.31; pxa0=xa00.37). Perhexiline therapy also led to an improvement in New York Heart Association functional class compared with placebo (pxa0= 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.nnnCONCLUSIONSnPerhexiline 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).

The Safety and Effects of Bosentan in Patients with a Fontan Circulation

OBJECTIVEnu2002 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.nnnDESIGNnu2002 A 6-month prospective, single-center, pilot, safety study of bosentan in Fontan patients. Setting.u2002 Adult Congenital Heart Disease referral center.nnnPATIENTSnu2002 All patients ≥18 years old with a Fontan circulation and in NYHA FC ≥II were invited to enroll. Interventions.u2002 Patients started on 62.5u2003mg bid of bosentan, uptitrating to 125u2003mg bid after 2 weeks.nnnOUTCOME MEASURESnu2002 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.nnnRESULTSnu2002 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.nnnCONCLUSIONSnu2002 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.

Long-term Outcome Following Pregnancy in Women with a Systemic Right Ventricle: Is the Deterioration due to Pregnancy or a Consequence of Time?

INTRODUCTIONnThe 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.nnnMETHODSnWomen 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.nnnRESULTSnEighteen 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.nnnCONCLUSIONnThis 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 reviewThere 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 findingsThe 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. SummaryThese 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.

Patient experience within the adult congenital heart disease outreach network: a questionnaire-based study

BackgroundSpecialist multi-disciplinary care improves outcomes of Adult Congenital Heart Disease (ACHD) patients. Following the NHS England Congenital Heart Disease standards review, the aim is to deliver high quality, patient-centred, care closer to patients’ homes. Cardiac investigations performed on the same day of outpatient appointments reduce the non-attendance rates. This young cohort of patients, benefits from comprehensive multi-disciplinary management. We developed a Patient Questionnaire across our West Midlands ACHD network to measure patient experience.MethodsPatient questionnaires were distributed to patients attending outpatient clinics in all 8 Outreach Centres and the Level 1 ACHD Centre (University Hospitals Birmingham).Results71 males (55%) and 59 females (45%), median age range 25–34xa0years old (range between 16 and 75xa0years old), returned the questionnaires (nu2009=u2009130).Most patients travelled less than one hour to hospital (93%, nu2009=u2009120) and less than 20xa0miles (86%, nu2009=u200999). The mean travel distance was 14u2009±u200912.3xa0miles (range 1 to 160xa0miles), with Level 1 ACHD Centre patients travelling a significantly longer distance (mean 29.6u2009±u200944xa0miles) compared to the local Outreach Centres (mean 11.3u2009±u20099xa0miles, pu2009=u20090.0037).There was a wide variability in the provision of parking, although most patients found the appointment time and location convenient (91%, nu2009=u2009117 and 95%, nu2009=u2009121 respectively).There was also marked variation in the number of electrocardiograms (19–100%) and echocardiograms (0–60%) performed on the same day as their clinic appointment.Most patients felt they were given enough information regarding their condition (85%, nu2009=u200998), with no significant differences between the centres (pu2009=u20090.24).ConclusionTo our knowledge, this is the first questionnaire-based study assessing patient experience within the NHS ACHD Outreach network with significantly reduced travel times and maintained high patient satisfaction. There was a wide variation in investigations performed and patient information leaflets provided. Standardisation of services is required at all centres to ensure equity of care, with Specialist Nurses’ input and more availability of tests on the day of clinic appointments in all centres.

73 Maternal and Fetal Outcomes in Women with Aortopathy: Experience in a Tertiary Joint Cardiac Obstetric Centre

Introduction Pregnancy is associated with increased risk of cardiovascular complication for women with aortic pathology. The University Hospitals Birmingham (UHB) and Birmingham Women’s Hospital (BWH) joint cardiac obstetric service sees women with aortopathy for pre-pregnancy assessment and counselling and subsequently manages them during pregnancy. A 10% incidence of serious maternal complications during pregnancy is widely quoted. We sought to review our recent cases and describe maternal and fetal outcomes in our patient population. Methods Female patients aged 16–35 with aortopathy and a recent pregnancy (2008 � 2015) were identified from the UHB database. Patients with a bicuspid aortic valve, structural congenital cardiac disease and coarctation of the aorta were excluded. Electronic and paper patient records and imaging results were reviewed to collect data regarding diagnosis, medical management, aortic dimensions, maternal obstetric and cardiovascular complications during or subsequent to pregnancy (within 1 year) and fetal outcome. Results 23 patients were identified with the following diagnoses: Marfan syndrome (n = 14), Ehlers-Danlos (n = 4), Loeys-Dietz (n = 1) and undefined (n = 4) aortopathy. There were no patients with Turner syndrome within this cohort. One patient was excluded as she was under follow up for a family history of aortic disease which did not subsequently manifest itself in the patient. There were a total of 28 pregnancies. Beta blockers were prescribed in 21 pregnancies. Magnetic resonance imaging (MRI or MRA) was performed in 17 pregnancies. Maternal outcomes Two patients had aortic dissections related to pregnancy. One was diagnosed immediately post partum in a woman with known Marfan syndrome and the other at 38 weeks gestation in a woman subsequently found to have to have Marfan syndrome. Both had successful emergency aortic root replacement, the second immediately after delivery of the fetus by caesarean section. One patient with undefined aortopathy presented acutely with chest pain and a rapidly dilating aorta; she had an emergency aortic root replacement at 22/40 gestation and was found to have a necrotising granulomatous aortitis. No patients died. Two patients had a change in aortic dimensions noted during pregnancy. Fetal outcomes Two of the pregnancies resulted in therapeutic abortions related to occurrence of inherited lesions in the fetus. Conclusion Although our numbers are small, the incidence of complications during pregnancy or immediately post partum are similar to those that we quote to our patients. Pregnant and post partum women complaining of severe chest pain should be brought to the immediate attention of senior staff and investigated urgently.

P2 Outcomes in adults following anatomic repair of congenitally corrected transposition of the great arteries

Introduction Anatomic repair (double switch operation) for congenitally corrected transposition of the great arteries (ccTGA) is associated with good short to mid-term outcomes. An increasing number of these patients are surviving to adulthood. There is a paucity of data in adults regarding late sequelae. We sought to determine the long-term outcomes in older patients who have previously undergone a double switch operation for ccTGA. Methods A retrospective analysis of 16 patient records from 2001 to 2015 from a single institution was conducted. Median age was 23 years (range 18–56 years, 14 male). Six patients had undergone a Senning-arterial switch and 10 patients underwent a Rastelli-Senning procedure. Associated defects included VSD (n = 13), pulmonary stenosis (n = 2) and pulmonary atresia (n = 13). Three patients had undergone prior pulmonary artery banding and 7 patients systemic-pulmonary artery shunting. We determined freedom from re-operation/intervention, development of systemic left ventricular (LV) dysfunction, systemic mitral regurgitation, conduction disorders and arrhythmias. Results Median follow-up was 19 years (18–21 years). Eleven patients required further surgery with 4 patients having undergone two subsequent operations. Following anatomic repair, median time to 1st operation was 11 years (7–13 years). Indications for re-operation included re-do RV-PA conduit in the Rastelli-Senning patients (n = 8) and aortic valve replacement in the Senning-arterial group (n = 3). 5 patients developed atrio-ventricular conduction block requiring a pacemaker. Three patients developed atrial arrhythmias, with 2 requiring ablation procedures. Six patients developed LV dysfunction. There were no deaths or need for cardiac transplantation in this series. Conclusion The majority of patients required a second operation, largely in the Rastelli-Senning group. In the Senning-arterial group, late aortic valve insufficiency occurred in 50% of the patients. Conduction disease and atrial arrhythmias contribute to late morbidity in these patients. Nevertheless, the majority of patients are free of heart failure. Despite good short-term outcomes and survival following anatomic repair, careful long-term evaluation for structural and electrophysiological abnormalities is required.

P29 Management and follow up in patients with a fontan circulation: are we following esc guidelines?

Introduction A Fontan procedure is a palliative surgical approach for patients whose congenital heart defects mean they have a single ventricle. Lifelong, specialist follow up for these complex patients is crucial. The European Society of Cardiology (ESC) guidelines (2010) recommend an annual review carried out at a specialised Grown Up Congenital Heart (ACHD) centre that should include an ECG, echocardiogram and exercise testing, and blood tests covering haematology, serum albumin, renal function and liver function, as well as cardiac MRI and liver ultrasounds are carried out at appropriate intervals. Methods A retrospective analysis of Fontan patients at a large quaternary Specialist ACHD centre over the past three years using patient notes was performed. Results Data was collected on 214 patients; 45% (n = 96) were female and 55% (n = 118) male. The mean age of the cohort was 28 +/- 9.27 years (range=17–68 years). 20 (9%) patients had died by the time of audit. 49% (n = 105) had a Modified AP Fontan, 41% (n = 87) had a TCPC Fontan and 10% (n = 22) had a Lateral Tunnel Fontan. The mean age at time of Fontan procedure was 8 +/- 7.69 years (range = 1–52 years). In 2014, most patients, 81% (n = 158) of patients had a specialist review appointment. 69% (n = 134) had an ECG and over half, 55% (n = 107) had an echo. Only 46 patients (29%) underwent CPEX testing. Only 26% of patients (n = 50) had a liver ultrasound. Almost a third of patients, 29% (n = 48) had a cardiac MRI (27 patients contraindicated due to pacemakers/ICD). 53% (n = 102) had haematology bloods performed, 56% (n = 109) had serum creatinine, 56% (n = 108) had serum albumin and liver function tests and 42% (n = 81) had alpha-fetoprotein bloods. Over the 3 year period, 25 Fontan patients (13%) had abnormal liver function blood tests, but did not attend for a liver ultrasound. Conclusions Although the guidelines are not being fulfilled, a number of patients do not attend for their recommended appointments. We propose an annual one-stop specialist Fontan clinic, to try and minimise appointments and improve adherence to guidelines. We also propose that these recommendations should be re-assessed to see if they are realistic, such as the need for an annual echocardiogram in a clinically stable patient and how they could be adapted, especially in a young cohort, many of whom are in full time education or employment. Updating these Guidelines and a one-stop specialist clinic may accommodate this unique population and could improve patient care as well as reduce DNA rates for multiple appointments.

139 Reduced Aortic Distensibility and Adverse Cardiovascular Functional Performance in Adult Patients with Single Ventricular Physiology

Introduction Children with reconstructed aortas performed for palliation in hypoplastic left heart syndrome (HLHS) have reduced aortic distensibility and unfavourable arterial-ventricular coupling. The impact of these changes on ventricular function and cardiovascular functional performance in surviving adults with single ventricular physiology remains unknown. Methods Cardiac MRI (1.5T) was performed in 10 patients (mean age 19 years ± 2) with HLHS who had undergone aortic reconstruction in childhood, 10 age and gender matched patients with single ventricle physiology but without aortic reconstruction and 10 age and gender matched diabetic controls subjects. Aortic distensibility (defined as (maximum aortic area – minimum aortic area/minimum aortic area)/pulse pressure)) was assessed in the mid ascending aorta throughout the cardiac cycle using steady state free precession imaging and analysed using Matlab software. Congenital patients also underwent routine cardiopulmonary exercise testing (RAMP protocol) to asses parameters of cardiovascular functional performance. Results Patients with HLHS had reduced aortic distensibility compared with patients with single ventricular physiology and diabetics (2.13 10–3 mmHg ± 1.26 vs. 3.9 10–3 mmHg ± 1.41 vs. 7.3 10–3 mmHg ± 1.38, p < 0.01) Figure 1. There were no differences in univentricular volumes or ejection fraction between HLHS and other single ventricular physiology (EF 55% ± 8 vs. 60 ± 5, p = 0.12). All patients with single ventricular physiology had marked cardiac limitation. Functional restriction was more severe in HLHS although did not reach statistical significance; predicted VO2 max for age and gender 55% ± 18 vs. 60% ± 20 (p = 0.16), reduced cardiac work load 9.27 METS ± 3.6 vs. 10.4 METS ± 3.5 (p = 0.47), VE/VCO2 slope < 35 n = 6 vs. n = 3 (p = 0.68). Abstract 139 Figure 1 Box scatter plot of aortic distensibility in patients with single ventricular physiology compared with matched diabetic subjects Conclusion Adults with reconstructed aortas in hypoplastic left heart syndrome have reduced aortic distensibility and impaired prognostic markers of functional cardiovascular performance before changes in ejection fraction. The potential impact of these findings warrants further study.

95 Impaired cardiac energetics in dilated cardiomyopathy: magnetic resonance spectroscopy at 3T

Introduction The aim was to measure the cardiac phosphocreatine to ATP (PCr/ATP) ratio non-invasively in patients with dilated cardiomyopathy and normal controls, and to correlate the patients results to symptom status, ejection fraction (EF) and quality of life scores. Dilated cardiomyopathy is known to be associated with cardiac energy deficiency. Magnetic resonance spectroscopy (MRS) has been proposed as a non-invasive method of assessing cardiac energetics and as a method of measuring response to therapy. Interrogation at high field strength improves signal to noise ratio. Methods 32 patients and 22 control subjects were studied using phosphorus-31 (31P) MRS and patients were classified to NYHA symptom class. In vivo energetics were measured using a commercially available Philips Achieva 3 Tesla scanner and dedicated 31P coil with ISIS volume selection. Java Magnetic Resonance User Interface (jMRUI) was used for analysis. Furthermore, all patients completed a Minnesota Living with Heart Failure (MLWHF) score and underwent echocardiography. LVEF was measured using biplane Simpsons method. Results The PCr/ATP ratio was significantly reduced in patients (1.35±0.31) compared with control subjects (1.90±0.40; p<0.005). The PCr/ATP ratio was correlated with NHYA class (r=−0.68, n=32, p<0.0005). No correlation was found with LVEF or MLWHF score. Conclusions This study confirms the presence of energy deficiency in dilated cardiomyopathy as measured by MRS at 3T. The energy status correlates strongly with symptom status but not with ejection fraction nor quality of life score. Cardiac energetic status is directly proportional to symptoms status and therefore any treatments targeted to improve cardiac energetics may improve patient symptoms in dilated cardiomyopathy.Abstract 95 Figure 1 Abstract 95 Figure 2