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.

'The imitation game': a heart failure case report with a great diagnostic twist.

Background: Arrhythmogenic ventricular cardiomyopathy (AVC) is a hereditary cardiomyopathy that has been associated with mutations in genes encoding for components of the cardiac desmosome including desmoglein-2 (DSG-2). Case summary: A 49-year-old male presented with decompensated heart failure and ventricular arrythmias. A cardiac magnetic resonance scan demonstrated a dilated left ventricle (LV) with severely impaired systolic function and extensive subepicardial late gadolinium enhancement in the lateral wall. An 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan identified myocardial uptake consistent with inflammation. Following treatment with steroids for presumed cardiac sarcoidosis, a repeat FDG-PET confirmed resolution of inflammation. A dilated cardiomyopathy/AVC gene panel, however, subsequently identified a pathogenic variant in the DSG-2 gene. Discussion: We describe the case of a patient presenting with clinical and imaging features suggestive for cardiac sarcoidosis, however genetic testing established a diagnosis of DSG-2 associated AVC. DSG-2 mutations in AVC are associated with frequent LV involvement and heart failure. Active inflammation has been observed in other cardiomyopathies, specifically in desmoplakin cardiomyopathy which has a similar clinical course to DSG-2. To our knowledge, this is the first case of DSG-2 cardiomyopathy presenting in this manner. We encourage clinicians to have a high index of suspicion of inflammatory cardiomyopathies as a differential to myocarditis and cardiac sarcoidosis, when patients present with evidence of decompensated heart failure, arrhythmias, and active myocardial inflammation.

Characterizing left ventricular systolic dysfunction in sickle cell disease: three contrasting case reports.

Background: Left ventricular systolic dysfunction (LVSD) is an uncommon but life-threatening complication of sickle cell disease (SCD), with poorly characterized aetiology. We present three SCD patients with LVSD due to different underlying mechanisms. Case summary: The first case describes rapid deterioration in LV function secondary to severe cardiac iron overload in a 37-year-old female with poor chelation compliance after 10 years of top-up transfusions for SCD. The second case is a severe non-ischaemic dilated cardiomyopathy (DCM) in a 42-year-old SCD patient with longstanding sickle nephropathy and hypertension. The final case demonstrates severe LVSD with large transmural infarcts (ischaemic DCM) in the absence of epicardial coronary disease in a 52-year-old SCD patient. Discussion: This case series presents the first attempt to characterize the aetiology of LVSD in SCD. We identified three phenotypes: iron-overload cardiomyopathy, non-ischaemic DCM, and ischaemic DCM. These contrasting cases highlight the significance of understanding the underlying pathology in determining individualized treatment plans for these high-risk patients. We discuss the role of cardiac MRI (CMR) in characterizing LV dysfunction, and we believe that this case series will form the basis of prospective studies to further delineate the pathophysiology of LVSD in SCD.

Pathogenic truncating filamin C mutations presenting as acute myocarditis: a case series with insights from cardiac magnetic resonance and histological analysis.

Background: The exact mechanisms underlying the pathogenesis of myocarditis are not always understood, but there is emerging evidence to suggest that genetic factors may play a significant role. Case summary: Herein, we present six cases in which clinical, biochemical, and cardiovascular magnetic resonance data were consistent with myocarditis, and genetic testing subsequently revealed pathogenic filamin C (FLNC) mutations. Three patients presented with ventricular arrhythmias, two with severe biventricular dysfunction, and two suffered sudden cardiac arrest. Three received an implantable cardioverter defibrillator, and one underwent heart transplantation. Cascade testing was useful in identifying other relatives with FLNC mutation. We also present relevant histology results of myocardial specimens showing the presence of lymphocytic infiltration and inflammation, further supporting the potential association between FLNC mutations and a myocarditis phenotype. Discussion: Genetic testing of affected individuals for FLNC mutations and cascade screening in the setting of acute myocarditis may be considered in selected clinical context, such as in acute myocarditis accompanied by severe left ventricular systolic dysfunction, biventricular failure, significant ventricular arrhythmias, or right ventricular involvement.

Aortic cusp perforation during rotational atherectomy: a case report.

Background: Rotational atherectomy has become increasingly utilised over the past decade. Although a relatively safe procedure in appropriately trained physicians' hands, there are a number of recognised complications. Case summary: We describe the case of a 64-year-old female who presented with chest pain and was diagnosed with non-ST-segment elevation acute coronary syndrome. A transthoracic echocardiogram (TTE) showed normal biventricular function and no valve disease. Invasive coronary angiogram was performed which revealed a severely calcified ostial right coronary artery (RCA) disease which was felt to be the culprit of the presentation. Balloon dilatation was unsuccessful, therefore, rotational atherectomy with an Amplatz left 0.75 guide and a 1.5 mm rota-burr was utilised and improved calcium burden. This was complicated by ostial dissection, treated with stenting. A TTE following the procedure revealed moderate aortic regurgitation (AR). The patient was discharged as she remained asymptomatic. An outpatient transoesophageal echocardiogram performed eight months later showed evidence of severe eccentric AR. Cardiac magnetic resonance imaging confirmed severe AR with left ventricular dilatation. Repeat angiogram 10 months after index procedure revealed in-stent restenosis, and the patient was accepted by heart multidisciplinary team for aortic valve replacement and grafting of RCA. Discussion: As the field of rotational atherectomy continues to expand, we propose that novel complications such as reported in this case may become recognised. Finally, we stress the importance of multi-modality imaging in the investigation and timely planning of interventions in the management of these patients.

Systematic review of the incidence and clinical risk predictors of atrial fibrillation and permanent pacemaker implantation for bradycardia in Fabry disease.

INTRODUCTION: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by enzyme deficiency, leading to glycosphingolipid accumulation. Cardiac accumulation triggers local tissue injury, electrical instability and arrhythmia. Bradyarrhythmia and atrial fibrillation (AF) incidence are reported in up to 16% and 13%, respectively. OBJECTIVE: We conducted a systematic review evaluating AF burden and bradycardia requiring permanent pacemaker (PPM) implantation and report any predictive risk factors identified. METHODS: We conducted a literature search on studies in adults with FD published from inception to July 2019. Study outcomes included AF or bradycardia requiring therapy. Databases included Embase, Medline, PubMed, Web of Science, CINAHL and Cochrane. The Risk of Bias Agreement tool for Non-Randomised Studies (RoBANS) was utilised to assess bias across key areas. RESULTS: 11 studies were included, eight providing data on AF incidence or PPM implantation. Weighted estimate of event rates for AF were 12.2% and 10% for PPM. Age was associated with AF (OR 1.05-1.20 per 1-year increase in age) and a risk factor for PPM implantation (composite OR 1.03). Left ventricular hypertrophy (LVH) was associated with AF and PPM implantation. CONCLUSION: Evidence supporting AF and bradycardia requiring pacemaker implantation is limited to single-centre studies. Incidence is variable and choice of diagnostic modality plays a role in detection rate. Predictors for AF (age, LVH and atrial dilatation) and PPM (age, LVH and PR/QRS interval) were identified but strength of association was low. Incidence of AF and PPM implantation in FD are variably reported with arrhythmia burden likely much higher than previously thought. PROSPERO DATABASE: CRD42019132045.

The role of multi-modality cardiovascular imaging in a patient presenting with acute liver failure secondary to constrictive pericarditis: a case report.

Background: Constrictive pericarditis is a rare cause of heart failure which often presents a diagnostic challenge to clinicians. Case summary: We describe the case of a 62-year-old male who presented to our institution with symptoms and signs suggestive of acute liver failure. Abdominal imaging demonstrated congestive hepatopathy. Clinical suspicion despite a 'normal' echocardiogram and sub-threshold NT-proBNP led to multi-modality cardiovascular imaging investigations to determine the cause of the heart failure syndrome. His cardiovascular magnetic resonance scan confirmed ventricular interdependence and extensive late enhancement in the pericardium with associated pericardial effusion. An 18F-fluorodeoxyglucose-positron emission tomography scan confirmed active pericardial inflammation. Cardiac computed tomography showed minimal pericardial calcification. Following confirming the diagnosis of effusive-constrictive pericarditis with evidence of active pericardial inflammation on imaging, a discussion within the Heart multidisciplinary team concluded that a trial of medical therapy with steroids is justifiable to avoid high-risk pericardiectomy. The patient was successfully treated with a combination of ibuprofen, colchicine, and prednisolone resulting in clinical improvement and remission of his symptoms. The imaging investigations were repeated 6 months later and confirmed radiological remission and medical therapy was discontinued. Discussion: We stress the importance of multi-modality cardiovascular imaging in the diagnosis of constrictive pericarditis and also emphasize its role in identifying the subset of patients who may respond to medical therapy, therefore reducing the risk of high need surgical pericardiectomy.

Challenges of remote consultations: a delayed diagnosis of aortic valve endocarditis complicated by recurrent intracranial events.

Embolic events causing stroke and intracranial haemorrhage are among the most catastrophic complications of infective endocarditis (IE).A female patient presented with acute unilateral weakness following a 3-month history of fever, for which she had multiple remote consultations with her general practitioner. A brain MRI confirmed a left sided infarct with haemorrhagic transformation. Blood cultures grew Streptococcus mitis and her cardiac imaging showed an aortic valve vegetation with severe aortic regurgitation. Following 2 weeks of antibiotics she developed a new cerebral haemorrhage associated with a mycotic aneurysm which was treated with two coils. After discussions within the multidisciplinary meeting, she underwent aortic valve replacement 3 weeks later. She made a remarkable recovery and was discharged.Our case highlights the importance of face-to-face clinical review in the post-COVID era. It stresses that the management of patients with infective endocarditis and neurological complications is challenging and requires a multidisciplinary approach.

Mid-term follow-up and outcomes of patients with prosthetic heart valves: a single-centre experience.

BACKGROUND: Patients with prosthetic heart valves (PHV) require long-term follow-up, usually within a physiologist led heart valve surveillance clinic. These clinics are well established providing safe and effective patient care. The disruption of the COVID-19 pandemic on services has increased wait times thus we undertook a service evaluation to better understand the patients currently within the service and PHV related complications. METHODS: A clinical service evaluation of the heart valve surveillance clinic was undertaken to assess patient demographics, rates of complications and patient outcomes in patients who had undergone a PHV intervention at our institute between 2010 and 2020. RESULTS: A total of 294 patients (mean age at time of PHV intervention: 71 ± 12 years, 68.7% male) were included in this service evaluation. Follow-up was 5.9 ± 2.7 years (range: 10 years). 37.1% underwent baseline transthoracic echo (TTE) assessment and 83% underwent annual TTE follow-up. Significant valve related complications were reported in 20 (6.8%) patients. Complications included a change in patient functional status secondary to significant PHV regurgitation (0.3%) or stenosis (0.3%), PHV thrombosis (0.3%) or infective endocarditis (3.7%). Significant valve related complications resulted in ten hospital admission (3.4%), two re-do interventions (0.6%), and four deaths (1.3%). CONCLUSIONS: This service evaluation highlights the large number of patients requiring ongoing surveillance. Only a small proportion of patients develop significant PHV related complications resulting in a low incidence of re-do interventions and deaths.

MINOCA-induced apical ballooning case report: a diagnostic conundrum.

BACKGROUND: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a recently described phenomenon where no flow-limiting lesions are noted on coronary angiography in a patient with electrocardiogram changes, elevated cardiac biomarkers, and symptoms suggesting acute myocardial infarction. Patients with MINOCA can also potentially develop structural cardiac defects through ischaemic injury. Therefore, the absence of a flow-limiting lesion on angiography coupled with structural defects (e.g. apical ballooning) can very easily result in a diagnosis of Takotsubo cardiomyopathy (TTC). This can lead to potentially serious consequences since treatment options between TTC and MINOCA are different. CASE SUMMARY: We report a case of a patient presenting with features suggestive of TTC but where the final diagnosis was of a MINOCA that induced an apical ventricular septal defect (VSD). Reaching the correct diagnosis proved challenging given that there is no gold standard diagnostic modality for diagnosing MINOCA. CONCLUSION: Imaging adjuncts played a vital role in both diagnosing the underlying MINOCA as well as revealing and planning closure of the resultant VSD. Cardiovascular magnetic resonance imaging played an instrumental role in establishing the patient's primary pathology and in planning a remediation of the structural defect. Structural myocardial defects in a patient with a diagnosis of TTC should prompt clinicians to further investigate whether there is an underlying infarct aetiology (MINOCA).

When multimodality cardiac imaging saves the day: rare cause of embolic strokes.

Hypereosinophilic syndrome (HES) is a rare disorder characterised by eosinophilic infiltration of tissues. Myocardial infiltration occurs in 50%-60% of HES and leads to a condition called Loeffler's endocarditis. This can lead to endomyocardial injury with resultant superimposed thrombus formation and embolic stroke. We describe the case of a 57-year-old female patient presenting with neurological symptoms who was found to have multiple embolic strokes on a background of long-standing eosinophilia. Following a series of investigations, including transthoracic and transoesophageal echocardiographies and cardiovascular MRI, she was confirmed to have Loeffler's endocarditis with left ventricular thrombus. She was treated successfully with steroids and anticoagulation. We describe the pathophysiology of HES and Loeffler's endocarditis and stress the crucial role of multimodality cardiac imaging in establishing its diagnosis and treatment monitoring.

Impulse control disorders following deep brain stimulation of the subthalamic nucleus in Parkinson's disease: clinical aspects.

Parkinson's disease (PD) has been associated with the development of impulse control disorders (ICDs), possibly due to overstimulation of the mesolimbic system by dopaminergic medication. Preliminary reports have suggested that deep brain stimulation (DBS), a neurosurgical procedure offered to patients with treatment-resistant PD, affects ICD in a twofold way. Firstly, DBS allows a decrease in dopaminergic medication and hence causes an improvement in ICDs. Secondly, some studies have proposed that specific ICDs may develop after DBS. This paper addresses the effects of DBS on ICDs in patients with PD. A literature search identified four original studies examining a total of 182 patients for ICDs and nine case reports of 39 patients that underwent DBS and developed ICDs at some point. Data analysis from the original studies did not identify a significant difference in ICDs between patients receiving dopaminergic medication and patients on DBS, whilst the case reports showed that 56% of patients undergoing DBS had poor outcome with regards to ICDs. We discuss these ambivalent findings in the light of proposed pathogenetic mechanisms. Longitudinal, prospective studies with larger number of patients are required in order to fully understand the role of DBS on ICDs in patients with PD.