Repaired coarctation of the aorta, persistent arterial hypertension and the selfish brain.

BACKGROUND: It has been estimated that 20-30% of repaired aortic coarctation (CoA) patients develop hypertension, with significant cardiovascular morbidity and mortality. Vertebral artery hypoplasia (VAH) with an incomplete posterior circle of Willis (ipCoW; VAH + ipCoW) is associated with increased cerebrovascular resistance before the onset of increased sympathetic nerve activity in borderline hypertensive humans, suggesting brainstem hypoperfusion may evoke hypertension to maintain cerebral blood flow: the "selfish brain" hypothesis. We now assess the "selfish brain" in hypertension post-CoA repair. METHODS: Time-of-flight cardiovascular magnetic resonance angiography from 127 repaired CoA patients (34 ± 14 years, 61% male, systolic blood pressure (SBP) 138 ± 19 mmHg, diastolic blood pressure (DBP) 76 ± 11 mmHg) was compared with 33 normotensive controls (42 ± 14 years, 48% male, SBP 124 ± 10 mmHg, DBP 76 ± 8 mmHg). VAH was defined as < 2 mm and ipCoW as hypoplasia of one or both posterior communicating arteries. RESULTS: VAH + ipCoW was more prevalent in repaired CoA than controls (odds ratio: 5.8 [1.6-20.8], p = 0.007), after controlling for age, sex and body mass index (BMI). VAH + ipCoW was an independent predictor of hypertension (odds ratio: 2.5 [1.2-5.2], p = 0.017), after controlling for age, gender and BMI. Repaired CoA subjects with VAH + ipCoW were more likely to have difficult to treat hypertension (odds ratio: 3.3 [1.01-10.7], p = 0.049). Neither age at time of CoA repair nor any specific repair type were significant predictors of VAH + ipCoW in univariate regression analysis. CONCLUSIONS: VAH + ipCoW predicts arterial hypertension and difficult to treat hypertension in repaired CoA. It is unrelated to age at time of repair or repair type. CoA appears to be a marker of wider congenital cerebrovascular problems. Understanding the "selfish brain" in post-CoA repair may help guide management. JOURNAL SUBJECT CODES: High Blood Pressure; Hypertension; Magnetic Resonance Imaging (MRI); Cardiovascular Surgery; Cerebrovascular Malformations.

Success in a Fontan pregnancy: how important is ventricular function?

The Fontan operation is a palliative surgical procedure for patients whose hearts cannot support a biventricular circulation. The haemodynamic changes that occur in pregnancy are particularly challenging for Fontan patients and the outcomes are variable. We present a case where fetal outcome was particularly poor despite a lack of high risk features pre-pregnancy.

Coronary Stenosis and Cardiogenic Shock Secondary to Aortitis Following Aortic Root Support Procedure.

A woman with recent personalized external aortic root support implant presented in cardiogenic shock with bilateral coronary ostial occlusion and aortic inflammation requiring emergency coronary angioplasty. Subsequent computed tomography with positron emission tomography scanning demonstrated aortitis with extensive inflammation adjacent to the personalized external aortic root support mesh, the first report of this important complication.

Expanding the clinical spectrum of biglycan-related Meester-Loeys syndrome.

Pathogenic loss-of-function variants in BGN, an X-linked gene encoding biglycan, are associated with Meester-Loeys syndrome (MRLS), a thoracic aortic aneurysm/dissection syndrome. Since the initial publication of five probands in 2017, we have considerably expanded our MRLS cohort to a total of 18 probands (16 males and 2 females). Segregation analyses identified 36 additional BGN variant-harboring family members (9 males and 27 females). The identified BGN variants were shown to lead to loss-of-function by cDNA and Western Blot analyses of skin fibroblasts or were strongly predicted to lead to loss-of-function based on the nature of the variant. No (likely) pathogenic missense variants without additional (predicted) splice effects were identified. Interestingly, a male proband with a deletion spanning the coding sequence of BGN and the 5' untranslated region of the downstream gene (ATP2B3) presented with a more severe skeletal phenotype. This may possibly be explained by expressional activation of the downstream ATPase ATP2B3 (normally repressed in skin fibroblasts) driven by the remnant BGN promotor. This study highlights that aneurysms and dissections in MRLS extend beyond the thoracic aorta, affecting the entire arterial tree, and cardiovascular symptoms may coincide with non-specific connective tissue features. Furthermore, the clinical presentation is more severe and penetrant in males compared to females. Extensive analysis at RNA, cDNA, and/or protein level is recommended to prove a loss-of-function effect before determining the pathogenicity of identified BGN missense and non-canonical splice variants. In conclusion, distinct mechanisms may underlie the wide phenotypic spectrum of MRLS patients carrying loss-of-function variants in BGN.

Transthoracic Echocardiographic Assessment of the Heart in Pregnancy-a position statement on behalf of the British Society of Echocardiography and the United Kingdom Maternal Cardiology Society.

Pregnancy is a dynamic process associated with profound hormonally mediated haemodynamic changes which result in structural and functional adaptations in the cardiovascular system. An understanding of the myocardial adaptations is important for echocardiographers and clinicians undertaking or interpreting echocardiograms on pregnant and post-partum women. This guideline, on behalf of the British Society of Echocardiography and United Kingdom Maternal Cardiology Society, reviews the expected echocardiographic findings in normal pregnancy and in different cardiac disease states, as well as echocardiographic signs of decompensation. It aims to lay out a structure for echocardiographic scanning and surveillance during and after pregnancy as well as suggesting practical advice on scanning pregnant women.

Case of placental insufficiency and premature delivery in a Fontan pregnancy: physiological insights and considerations on risk stratification.

OBJECTIVES: The coexistence of two complex physiologies such as Fontan and pregnancy is still not fully understood. We aim to add a unique and essential knowledge to help our colleagues in the management of Fontan patients that undergo pregnancy as well as the fetus and the placenta perfusion. METHODS AND RESULTS: We analyse the coexistence of Fontan and pregnancy physiology on a complex case of a woman with hypoplastic left heart syndrome palliated with a univentricular repair who became pregnant, delivered very prematurely and had atypical placental findings. CONCLUSION: Histopathological analysis of the placenta could help us to refine the understanding of Fontan physiology adaptation during pregnancy, predict women and fetal outcomes as well as to plan a better pre-pregnancy status. However, further evidence is needed in order to reach a more solid and unified conclusion.

Wave Reflection and Ventriculo-Arterial Coupling in Bicuspid Aortic Valve Patients With Repaired Aortic Coarctation.

BACKGROUND: Ventriculo-arterial (VA) coupling in bicuspid aortic valve (BAV) patients can be affected by the global aortopathy characterizing BAV disease and the presence of concomitant congenital lesions such as aortic coarctation (COA). This study aimed to isolate the COA variable and use cardiovascular magnetic resonance (CMR) imaging to perform wave intensity analysis non-invasively to shed light on VA coupling changes in BAV. The primary hypothesis was that BAV patients with COA exhibit unfavorable VA coupling, and the secondary hypothesis was that BAV patients with COA exhibit increased wave speed as a marker of reduced aortic distensibility despite successful surgical correction. METHODS: Patients were retrospectively identified from a CMR database and divided into two groups: isolated BAV and BAV associated with repaired COA. Aortic and ventricular dimensions, global longitudinal strain (GLS), and ascending aortic flow data and area were collected and used to derive wave intensity from CMR data. The main variables for the analysis included all wave magnitudes (forward compression/expansion waves, FCW and FEW, respectively, and reflected backward compression wave, BCW) and wave speed. RESULTS: In the comparison of patients with isolated BAV and those with BAV associated with repaired COA (n = 25 in each group), no differences were observed in left ventricular ejection fraction, GLS, or ventricular volumes, whilst significant increases in FCW and FEW magnitude were noted in the BAV and repaired COA group. The FCW inversely correlated with age and aortic size. Whilst the BCW was not significantly different compared with that in patients with/without COA, its magnitude tends to increase with a lower COA index. Patients with repaired COA exhibited higher wave speed velocity. Aortic wave speed (inversely related to distensibility) was not significantly different between the two groups. CONCLUSION: In the absence of a significant restenosis, VA coupling in patients with BAV and COA is not negatively affected compared to patients with isolated BAV. A reduction in the magnitude of the early systolic FCW was observed in patients who were older and with larger aortic diameters.

Left heart matters in Ebstein's anomaly: the importance of a closer follow up-a case report.

BACKGROUND: Ebstein's anomaly (EA) is mainly thought of as a right heart condition, however, congenital left-sided lesions can co-exist. Therefore, it is paramount to include the left side of the heart as part of a routine investigation in these patients. We present a 57-year-old symptomatic patient with EA and progressive tricuspid regurgitation (TR) associated with acquired left ventricular outflow obstruction (LVOTO). CASE SUMMARY: A 57-year-old women, known to have severe EA presented with shortness of breath and chest pain on exertion secondary to progression of the tricuspid valve regurgitation and right ventricle dilatation leading to a dynamic compression of the left outflow tract requiring surgical intervention. DISCUSSION: Left ventricular obstruction secondary to severe TR and dilation of the right ventricle can present and remain silent at rest but becoming significant on exertion. Therefore, we recommend that all patients with EA and significant TR undergo exercise echocardiography at regular intervals to specifically look for acquired dynamic LVOTO.

Maternal and fetal outcomes in pregnancies complicated by Marfan syndrome.

OBJECTIVES: Information to guide counselling and management for pregnancy in women with Marfan syndrome (MFS) is limited. We therefore conducted a UK multicentre study. METHODS: Retrospective observational study of women with MFS delivering between January 1998 and March 2018 in 12 UK centres reporting data on maternal and neonatal outcomes. RESULTS: In total, there were 258 pregnancies in 151 women with MFS (19 women had prior aortic root replacements), including 226 pregnancies ≥24 weeks (two sets of twins), 20 miscarriages and 12 pregnancy terminations. Excluding miscarriages and terminations, there were 221 live births in 139 women. Only 50% of women received preconception counselling. There were no deaths, but five women experienced aortic dissection (1.9%; one type A and four type B-one had a type B dissection at 12 weeks and subsequent termination of pregnancy). Five women required cardiac surgery postpartum. No predictors for aortic dissection could be identified. The babies of the 131 (65.8%) women taking beta-blockers were on average 316 g lighter (p<0.001). Caesarean section rates were high (50%), particularly in women with dilated aortic roots. In 55 women, echocardiographic aortic imaging was available prepregnancy and postpregnancy; there was a small but significant average increase in AoR size of 0.84 mm (Median follow-up 2.3 months) CONCLUSION: There were no maternal deaths, and the aortic dissection rate was 1.9% (mainly type B). There with no identifiable factors associated with aortic dissection in our cohort. Preconception counselling rates were low and need improvement. Aortic size measurements increased marginally following pregnancy.

Acute thrombosis of a prosthetic mitral valve in pregnancy in spite of adjusted-dose low-molecular-weight heparin and aspirin.

A 31-year-old primigravida had a 27-mm CarboMedics mitral valve implanted previously for mitral regurgitation. The patient had decided to take low-molecular-weight heparin (LMWH) and aspirin throughout her pregnancy. Monthly echocardiography and anti-Factor Xa levels were satisfactory. She presented at 36 weeks' gestation with 24 h of exertional dyspnea, and was in pulmonary edema. Transthoracic echocardiography suggested valve thrombosis. The patient underwent mitral valve replacement after the vaginal delivery of a healthy infant. The resected valve was found to have adherent fresh thrombus. The recent recommendation that LMWH plus aspirin might provide adequate anticoagulation for mechanical valves in pregnancy does not prevent acute prosthetic mitral valve thrombosis.

Retrospective UK multicentre study of the pregnancy outcomes of women with a Fontan repair.

BACKGROUND: The population of women of childbearing age palliated with a Fontan repair is increasing. The aim of this study was to describe the progress of pregnancy and its outcome in a cohort of patients with a Fontan circulation in the UK. METHODS: A retrospective study of women with a Fontan circulation delivering between January 2005 and November 2016 in 10 specialist adult congenital heart disease centres in the UK. RESULTS: 50 women had 124 pregnancies, resulting in 68 (54.8%) miscarriages, 2 terminations of pregnancy, 1 intrauterine death (at 30 weeks), 53 (42.7%) live births and 4 neonatal deaths. Cardiac complications in pregnancies with a live birth included heart failure (n=7, 13.5%), arrhythmia (n=6, 11.3%) and pulmonary embolism (n=1, 1.9%). Very low baseline maternal oxygen saturations at first obstetric review were associated with miscarriage. All eight women with saturations of less than 85% miscarried, compared with 60 of 116 (51.7%) who had baseline saturations of ≥85% (p=0.008). Obstetric and neonatal complications were common: preterm delivery (n=39, 72.2%), small for gestational age (<10th percentile, n=30, 55.6%; <5th centile, n=19, 35.2%) and postpartum haemorrhage (n=23, 42.6%). There were no maternal deaths in the study period. CONCLUSION: Women with a Fontan circulation have a high rate of miscarriage and, even if pregnancy progresses to a viable gestational age, a high rate of obstetric and neonatal complications.

Heart Disease and Pregnancy.

Cardiac disease remains a major cause of morbidity and mortality in pregnant and post-partum women, although progress has been made, with specialist joint obstetric-cardiology clinics providing an integrated, safe and personalised service to these women. As a result, fewer non-specialist cardiologists are managing women in pregnancy with cardiovascular disease. The aim of this review is to provide a brief overview of current knowledge and practice in the field, with an emphasis on the major physiological changes which occur during pregnancy, focussing on progress through the trimesters, clinical assessment in pregnancy, management of delivery (concentrating on managed vaginal delivery), drug treatment, key conditions and risk assessment. The latter factor is particularly important in terms of being able to identify high-risk women earlier and to counsel them appropriately. Pregnant women with cardiovascular conditions can, with appropriate knowledge and counselling, be managed safely in specialist multidisciplinary services, but there is a need for cardiologists to understand the key changes and risks involved in pregnancy, delivery and the post-partum period.

Pregnancy outcome and follow-up cardiac outcome in women with aortic valve replacement.

OBJECTIVES: To compare the maternal, fetal and cardiac outcomes in women who have undergone aortic valve replacement. METHOD: Retrospective observational study of all women with aortic valve replacement, who underwent a pregnancy (1998-2012). Maternal-, fetal- and valve-related cardiac outcomes were assessed. RESULTS: Thirty-two pregnancies in 16 women with aortic valve replacement (nine bioprosthetic, six Ross and 17 mechanical) were evaluated. There were no adverse maternal events in the bioprosthetic and Ross groups but three in the mechanical group. Fetal loss rate was highest in the mechanical valve pregnancies (53%). One woman in the bioprosthetic group needed valve re-operation, and one woman in the mechanical valve group died. There was no difference in the change of Vmax over the follow-up between the valves (p = 0.25). CONCLUSIONS: There was no difference in deterioration between aortic valve replacements during and after pregnancy. The highest risk of maternal and fetal complications occurred in the mechanical valve group.

Balloon expandable stent implantation for native and recurrent coarctation of the aorta--prospective computed tomography assessment of stent integrity, aneurysm formation and stenosis relief.

BACKGROUND: Stenting for aortic coarctation is known to be effective in the medium term. Aneurysm formation following stent implantation is a recognised complication. However, data regarding aortic wall injury and stent integrity following stent placement are sparse. OBJECTIVES: We report comprehensive clinical, echocardiographic and prospective CT follow-up data following stenting for aortic coarctation from a single centre. Methods Full data analysis of all patients undergoing balloon expandable stent implantation and follow-up procedures in a single tertiary congenital cardiac unit. RESULTS: Between October 2002 and April 2008, we performed 102 coarctation stent procedures on 88 patients. Median age was 20.6 years (range 8.5-65) and median weight 65 kg (range 34-101). 94 stents (26 covered) were implanted. 12 procedures were re-dilatations. Stenting resulted in a reduction of the gradient across the site of coarctation, from a median of 20 mm Hg to 4 mm Hg. There were no procedure-related deaths. Four patients had immediate complications (one requiring emergency surgery). During median follow-up of 34.5 months (range 4.2-72.8), two patients had late complications requiring additional stent procedures. Follow-up CT data are available in 84 patients with MRI in one patient (96.5%). Only one patient developed a procedure-related aortic aneurysm. All stent fractures (n=7) occurred with a single stent design. CONCLUSIONS: Stenting for aortic coarctation and re-coarctation is effective with low immediate complication rates. CT is useful in the longer term for assessment of stent integrity and post-procedural aneurysm formation. Overall incidence of post-procedural aneurysm is rare and stent fractures were not seen with newer generation stents.

Current trends in the management of heart disease in pregnancy.

BACKGROUND: The management of heart disease in pregnancy is highly specialized. Guidelines are based on observational studies. This paper describes our experience of these patients, including adverse cardiac events, adherence to guidelines, and areas of suboptimal management. METHODS: Patients referred to the service between 01/05/1999 and 30/06/2005 were identified using clinic lists and keyword searches in databases. A list of 40 management standards was created from European Society of Cardiology and the Confidential Enquiry into Maternal and Child Health guidelines. Adherence to these was recorded and adverse cardiac events noted. RESULTS: There were 177 pregnancies in 155 women with a mean age of 28+/-6 years. Service referrals increased linearly throughout the study period. Of 131 cardiac pregnancies 101 had congenital heart disease (77.1%). Pulmonary oedema, deteriorating functional class, sustained arrhythmia or cardiac intervention occurred in 13 pregnancies (10.2%), though not always in high risk cases. Management guidelines were largely followed, though areas of suboptimal management included lack of pre-conception advice and inadequate post-partum follow-up. Controversial areas include the use of beta-blockade in coarctation of the aorta and the use of elective Caesarean section in high risk patients. CONCLUSIONS: Cardiac pregnancies are increasing, mainly due to the rise in patients with congenital heart disease. Some patients will experience adverse cardiac events, including low risk patients. Pre-conception advice and post-partum follow-up should be improved. In the absence of prospective studies, management is likely to be driven by observational studies.

Reduced systolic wave generation and increased peripheral wave reflection in chronic heart failure.

In human heart failure the role of wave generation by the ventricle and wave reflection by the vasculature is contentious. The aim of this study was to compare wave generation and reflection in normal subjects with patients with stable compensated heart failure. Twenty-nine normal subjects and 67 patients with heart failure (New York Heart Association class II or III) were studied by noninvasive techniques applied to the common carotid artery. Data were analyzed by wave intensity analysis to determine the nature and direction of waves during the cardiac cycle. The energy carried by an early systolic forward compression wave (S wave) generated by the left ventricle and responsible for acceleration of flow in systole was significantly reduced in subjects with heart failure (P < 0.001), and the timing of the peak of this wave was delayed. In contrast, reflection of this wave was increased in subjects with heart failure (P < 0.001), but the timing of reflections with respect to the S wave was unchanged. The energy of an expansion wave generated by the heart in protodiastole was unaffected by heart failure. The carotid artery wave speed and the augmentation index did not significantly differ between subjects with heart failure compared with normal individuals. The ability of the left ventricle to generate a forward compression wave is markedly impaired in heart failure. Increased wave reflection serves to maintain systolic blood pressure but also places an additional load on cardiac function in heart failure.