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Congenital heart disease (CHD) is the most common congenital anomaly, with an overall incidence of approximately 1% in the United Kingdom. Exome sequencing in large CHD cohorts has been performed to provide insights into the genetic aetiology of CHD. This includes a study of 1891 probands by our group in collaboration with others, which identified three novel genes—CDK13, PRKD1, and CHD4, in patients with syndromic CHD. PRKD1 encodes a serine/threonine protein kinase, which is important in a variety of fundamental cellular functions. Individuals with a heterozygous mutation in PRKD1 may have facial dysmorphism, ectodermal dysplasia and may have CHDs such as pulmonary stenosis, atrioventricular septal defects, coarctation of the aorta and bicuspid aortic valve. To obtain a greater appreciation for the role that this essential protein kinase plays in cardiogenesis and CHD, we have analysed a Prkd1 transgenic mouse model (Prkd1em1) carrying deletion of exon 2, causing loss of function. High‐resolution episcopic microscopy affords detailed morphological 3D analysis of the developing heart and provides evidence for an essential role of Prkd1 in both normal cardiac development and CHD. We show that homozygous deletion of Prkd1 is associated with complex forms of CHD such as atrioventricular septal defects, and bicuspid aortic and pulmonary valves, and is lethal. Even in heterozygotes, cardiac differences occur. However, given that 97% of Prkd1 heterozygous mice display normal heart development, it is likely that one normal allele is sufficient, with the defects seen most likely to represent sporadic events. Moreover, mRNA and protein expression levels were investigated by RT‐qPCR and western immunoblotting, respectively. A significant reduction in Prkd1 mRNA levels was seen in homozygotes, but not heterozygotes, compared to WT littermates. While a trend towards lower PRKD1 protein expression was seen in the heterozygotes, the difference was only significant in the homozygotes. There was no compensation by the related Prkd2 and Prkd3 at transcript level, as evidenced by RT‐qPCR. Overall, we demonstrate a vital role of Prkd1 in heart development and the aetiology of CHD. [ABSTRACT FROM AUTHOR]

We present a case of a 47-year-old female who presented with septic shock and a hyperosmolar hyperketotic state, accompanied by episodes of unresponsiveness. As part of the extensive investigations which took place, a transoesophageal echocardiogram (TOE) revealed infective endocarditis of the tricuspid, pulmonary and aortic valves. Blood cultures showed evidence of bacteraemia with Streptococcus agalactiae. After an initial improvement on intravenous antibiotics, the patient's condition deteriorated following multiple septic emboli to the lungs from the pulmonary valve vegetation, leading to urgent referral for valve replacement. A mechanical aortic, tissue pulmonary and tricuspid valve replacements were performed in a tertiary centre in the United Kingdom. The postoperative course was complicated by recurrent infections of the sternotomy wound with eventual wound dehiscence and overwhelming sepsis. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES Since percutaneous pulmonary valve implantation (PPVI) was introduced to prolong the lifetime of surgically placed right ventricular to pulmonary artery conduits, valve technology has evolved and the indications for PPVI expanded to native and larger right ventricular outflow tracts. We explore how indications, patient populations and outcomes compare to surgical pulmonary valve replacement (PVR). METHODS This is a retrospective cohort study of PPVI and PVR procedures between 1998 and 2020 at a single UK centre. One hundred and twenty-eight patients underwent PPVI and 365 patients PVR. Primary outcome measures were survival, infective endocarditis and reintervention. RESULTS The most common indication for PVR was replacement of the native pulmonary valve for pulmonary regurgitation whereas PPVI was more commonly used to treat pulmonary stenosis in a previously placed bioprosthetic conduit or valve. Treatment indications for PPVI expanded over the study to include the native right ventricular outflow tract. Survival was similar for PPVI and PVR (92% PPVI and 96.8% PVR at 5 years; 85.8% PPVI and 95.1% PVR at 10 years). Preprocedural New York Heart Association class 3 and 4 was the most important predictor of poor outcome. Annualized infective endocarditis rate was significantly higher for the Melody PPVI (0.024 vs 0.0024/person/year for PVR, P  < 0.05). Both groups showed significant symptomatic improvement postprocedure with remodelling of ventricular volumes and improvement in cardiac output. Long-term follow-up for PVR showed half of patients will need replacement at 10–15 years post-index procedure. CONCLUSIONS An increasing number of patients requiring PVR can now be treated percutaneously. A lifetime strategy for re-valving should be considered at the first valve implant. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES Many adults with repaired tetralogy of Fallot will require a pulmonary valve replacement (PVR), but there is no consensus on the best timing. In this study, we aim to evaluate the impact of age at PVR on outcomes. METHODS This is a national multicentre retrospective study including all patients >15 years of age with repaired tetralogy of Fallot who underwent their first PVR between 2000 and 2013. The optimal age cut-off was identified using Cox regression and classification and regression tree analysis. RESULTS A total of 707 patients were included, median age 26 (15–72) years. The mortality rate at 10 years after PVR was 4.2%, and the second PVR rate of 6.8%. Age at PVR of 35 years was identified as the optimal cut-off in relation to late mortality. Patients above 35 years of age had a 5.6 fold risk of death at 10 years compared with those with PVR under 35 years (10.4% vs 1.3%, P  < 0.001), more concomitant tricuspid valve repair/replacement (15.1% vs 5.7%, P  < 0.001) and surgical arrhythmia treatment (18.4% vs 5.9%, P  < 0.001). In those under 50 years, there was an 8.7 fold risk of late death compared with the general population, higher for those with PVR after 35 than those with PVR below 35 years (hazard ratio 9.9 vs 7.4). CONCLUSIONS Patients above 35 years of age with repaired tetralogy of Fallot have significantly worse mortality after PVR, compared with younger patients and a higher burden of mortality relative to the general population. This suggests that there are still cases where the timing of initial PVR is not optimal, warranting a re-evaluation of criteria for intervention. [ABSTRACT FROM AUTHOR]

The article discusses percutaneous pulmonary valve implantation with the Melody valve by Medtronic as indicated for regurgitant lesions. It outlines the patho-physiologhical criteria for selecting patients for implantation and discusses preprocedure assessment of patients. It also describes the procedure in detail, its intra and post operative complications and management.

Introduction: In patients with isolated pulmonary stenosis (iPS), dilatation of the MPA has been reported, sometimes developing into large aneurysms (giantPA). The incidence, aetiology, natural history, and its treatment. Methods: We identified all patients with iPS that attended our tertiary cardiac centre (one of the largest in the UK) between 2003 and 2018 and reviewed clinical notes, echocardiography and MRI data. We evaluated the incidence of MPA dilatation in patients with iPS and its relation to age and pulmonary valve (PV) function. Results: 197 patients (107 children, 90 adults) with iPS were identified. 122 (62%) underwent balloon dilatation of PV for severe stenosis (median age 0.65 IQR 0.08-5.18 years), 30 (15%) underwent PV repair or replacement (median age of 2.06 IQR 0.9-5.2 years) and 45 (22.8%) did not require any procedure. In patients that did not require a procedure, mean peak velocity on echocardiography was 2.55±0.65 m/sec. In patients that required an intervention, the MPA was normal to mildly dilated in most patients (mean z-score +1.2±2.6). In patients who did not undergo any procedure, the size of the MPA was only weakly correlated with age (R2.10 p <.01) and severity of PV stenosis (p <.22). 12 patients (6% of total population) had giantPA (z-score > 4 in children, diameter > 50 mm in adults). Mean size of the largest diameter of the MPA was +5.8±1.9 z-score in children and 59±5 mm in adults. Of these patient 58% had undergone a procedure (mean age 11±14 yrs). Of note, while in the paediatric cohort the MPA size was easily obtained using echocardiography, in only 30% of adult patients the MPA was well visualized and there was a significant error (25±27%) in the provided measurements compared to 3D imaging obtained with MRI. In 7 of 8 adults with giantPA , diagnosis was made only with MRI. Conclusion: In patients with iPS, the incidence of giantPA is not negligible (at least 6%). MPA dilatation does not seem to correlate with PV function thus suggesting an underlying arteriopathy rather than a flow-related aetiology. In adults, MPA size is unreliably assessed using echocardiography. 3D imaging is therefore indicated in adults patients with iPS even in the presence of mild PV dysfunction. Total; word count : 1875 characters Figure 1: No impact of stenosis severity on MPA size in patient who did not undergo PV repair or replacement Figure 2: Aneurysmal dilatation of the MPA in a patient with isolated pulmonary stenosis (in this case mild stenosis). [ABSTRACT FROM AUTHOR]