Heart failure and the cost of dying: must the ferryman always be paid?

BACKGROUND: Provision of palliative care in chronic heart failure (CHF) can support complex decision-making, significantly improve quality of life and may lower healthcare costs. AIMS: To examine whether healthcare costs differed in terminal admissions according to the adoption of a palliative approach. DESIGN: Retrospective review of medical records and costing data for all admissions resulting in death from CHF (July 2011 to December 2019), analysed as two groups (2011-2016 and 2016-2019) because of background changes in costings. SETTING: Admissions with CHF resulting in death in an Australian tertiary referral centre. RESULTS: The cohort (n = 439) were elderly (median age 83.7 years, interquartile range (IQR) = 77.6-88.7 years) and mostly men (54.9%). Half (230, 52.4%) were referred to a specialist palliative care team, whereas over a third (172, 39.2%) received a palliative approach. Receiving a palliative approach was associated with a nonstatistically significant lower admission cost (AU$12 710 vs AU$15 978; P = 0.19) between 2011 and 2016 (n = 101, 38.8%) and a significantly lower cost (AU$11 319 vs AU$15 978; P < 0.01) between 2016 and 2019 (n = 71, 39.7%). Intensive care admission resulted in the single greatest additional cost at AU$14 624 (IQR = AU$4130-AU$44 197) (n = 48, 2011-2016). Median terminal admission cost was lower for patients with comfort goals of care (P < 0.01), without life-sustaining interventions (P < 0.01) or who received a palliative approach (P < 0.01). Referral to inpatient specialist palliative care or receiving a palliative approach resulted in comparable admission costings (AU$11 621 [IQR = AU$4705-AU$32 457] and AU$11 466 [IQR = AU$4973-AU$25 614]). CONCLUSION: A palliative approach in terminal CHF admission may improve quality at the end of life and decrease costs associated with care.

The paradox of platypnoea-orthodeoxia syndrome.

Platypnoea-orthodeoxia is a rare clinical syndrome characterised by dyspnoea and oxygen desaturation in the upright position which improves when supine. It requires two components: a sufficiently sized anatomical vascular defect (typically intra-cardiac or intra-pulmonary) combined with a functional component that promotes positional right-to-left shunting. We describe the rare occurrence of a patient with platypnoea-orthodeoxia syndrome (POS) because of a paradoxical shunt through a patent foramen ovale caused by a large right atrial line-associated thrombus in a male with metastatic oesophageal cancer undergoing chemotherapy. This case is a timely reminder to consider POS amongst differentials for hypoxia as it is often treatable if recognised.

Palliative Care Utilisation and Outcomes in Patients Admitted for Heart Failure in a Victorian Healthcare Service.

BACKGROUND: Heart failure (HF) has high mortality and healthcare utilisation. It has a complex and unpredictable trajectory, which is often interpreted as a barrier to guideline recommended early integration of palliative care (PC). In particular, lack of referral criteria and misconceptions around PC affect inpatient specialist PC referrals. AIMS: The main objective was to characterise the pattern and predictors of referral of HF patients to the specialist inpatient PC consultative service at our healthcare service. METHODS: A retrospective, single-centre cohort study was performed on consecutive patients admitted across the hospital with HF over a 12-month period (July 2019-June 2020). Mortality data were checked against state death registry data. RESULTS: The 502 patients admitted for HF were elderly (mean age 78±14 years), had high dependency (54% Australian-modified Karnofsky Performance Status (AKPS) 50-70, 29% AKPS 10-40), and high mortality (53% within median 32 months at death registry data linkage). Seven per cent (7%) were referred to inpatient specialist PC. AKPS 10-40 (62% of those referred vs 26% not referred, p<0.01), reliance on carers (65% vs 36%, p<0.01), and New York Heart Association (NYHA) class III-IV symptoms (86% vs 42%, p<0.01) were associated with referral, but two or more admissions in the last 12 months for HF were not (16% vs 10%, p=0.21). Many PC domains, such as symptom burden, distress, and preferred care, were not adequately assessed. CONCLUSIONS: Referral to inpatient specialist PC in hospitalised HF patients is low relative to the morbidity and mortality in these patients.

Characteristics and Outcomes of a Single-Centre Cohort of Adult Congenital Heart Disease Patients Referred for Heart Transplant.

BACKGROUND: Adult congenital heart disease (ACHD) services increasingly encounter heart failure (HF) in the ageing ACHD population. Optimal timing of referral for heart transplant (HTx) evaluation in this heterogeneous population is complex and ill-defined. We aim to outline the characteristics and outcomes of ACHD patients referred for HTx from a large Australian ACHD centre. METHOD: Retrospective review of ACHD patients referred for HTx from a primary ACHD centre (1992-2021). Database analysis of patient demographics, characteristics, wait-listing, and transplantation outcomes was performed. RESULTS: A total of 45 patients (mean age 37±9.9 years old; 69% male) were referred for HTx with a mean follow-up of 5.9±6.3 years. Of these, 22 of 45 (49%) were listed and transplanted, including one heart-lung transplant. The commonest diagnosis was dextro-transposition of the great arteries (13/45, 29%). Most patients, 33 of 45 (73.3%) had undergone at least one cardiac surgery in childhood. Indications for HTx referral included HF in 34 of 45 (75%), followed by pulmonary hypertension in 7 of 45 (11%). Median transplant wait-list time was 145 days (interquartile range, 112-256). Of the 23 patients not wait-listed, the reasons included clinical stability in 13 of 45 (29%), psychosocial factors in 2 of 45 (4.4%) and prohibitive surgical risk, including multiorgan dysfunction, in 8 of 45 (17.7%). Transplant was of a single organ in most, 21 of 22 (95.5%). Overall mortality was 5 of 22 (22.7%) in those after HTx, and 14 of 23 (60.9%) in those not listed (p=0.0156). CONCLUSIONS: Increasingly, ACHD patients demonstrate the need for advanced HF treatments. HTx decision-making is complex, and increased mortality is seen in those not wait-listed. Ultimately, the referral of ACHD patients for HTx is underpinned by local decision-making and experience, wait-list times and outcomes.

Prolonged Enteral Tube Feeding in Infants With a Functional Single Ventricle Is Associated With Adverse Outcomes After Fontan Completion.

OBJECTIVES: To define the baseline characteristics of long-term tube-fed (TF) single ventricle patients, investigate associations between long-term enteral tube feeding and growth, and determine associations with long-term outcomes after Fontan procedure. STUDY DESIGN: We performed a retrospective cohort study of patients in the Australia and New Zealand Fontan Registry undergoing treatment at the Royal Children's Hospital, the Children's Hospital at Westmead, Royal Melbourne Hospital, and Royal Prince Alfred Hospital from 1981 to 2018. Patients were defined as TF or non-tube-fed (NTF) based on enteral tube feeding at the age of 90 days. Feeding groups were compared regarding body mass index (BMI) trajectory, BMI at last follow-up, and long-term incidence of severe Fontan failure. RESULTS: Of 390 patients (56 [14%] TF, 334 [86%] NTF), TF was associated with right ventricular dominance, hypoplastic left heart syndrome, Norwood procedure, increased procedures prior to Fontan, extracardiac conduit Fontan, Fontan fenestration, and atrioventricular valve repair/replacement. TF patients were less likely to be in the higher compared with lowest 0-6 month BMI trajectory (P < .01; P = .03), had lower 6 month weight-for-age z-scores (P < .01) and length-for-age z-scores (P = .01). TF were less likely to be overweight/obese at pediatric follow-up (hazard ratio [HR] = 0.31, 95% CI: 0.12-0.80; P = .02) and more likely to be underweight at adult follow-up (HR = 16.51; 5% CI: 2.70-101.10; P < .01). TF compared with NTF was associated with increased risk of severe Fontan failure (HR = 4.13; 95% CI = 1.65-10.31; P < .01). CONCLUSIONS: Prolonged infant enteral tube feeding is an independent marker of poor growth and adverse clinical outcomes extending long-term post-Fontan procedure.

Inconsistent discharge diagnoses for young cardiac arrest episodes: insights from a statewide registry.

BACKGROUND: Administrative coding of out-of-hospital cardiac arrest (OHCA) is heterogeneous, with the prevalence of noninformative diagnoses uncertain. AIM: To characterize the prevalence and type of non-informative diagnoses in a young cardiac arrest population. METHODS: Hospital discharge diagnoses provided to a statewide OHCA registry were characterised as either 'informative' or 'noninformative.' Informative diagnoses stated an OHCA had occurred or defined OHCA as occurring due to coronary artery disease, cardiomyopathy, channelopathy, definite noncardiac cause, or no known cause. Noninformative diagnoses were blank, stated presenting cardiac rhythm only, provided irrelevant information or presented a complication of the OHCA as the main diagnosis. Characteristics of patients receiving informative versus noninformative diagnoses were compared. RESULTS: Of 1479 patients with OHCA aged 1 to 50 years, 290 patients were admitted to 15 hospitals. Ninety diagnoses (31.0%) were noninformative (arrest rhythm = 50, blank = 21, complication = 10 and irrelevant = 9). Two hundred diagnoses (69.0%) were informative (cardiac arrest = 84, coronary artery disease = 54, noncardiac diagnosis = 48, cardiomyopathy = 8, arrhythmia disorder = 4 and unascertained = 2). Only 10 diagnoses (3.5%) included both OHCA and an underlying cause. Patients receiving a noninformative diagnosis were more likely to have survived OHCA or been referred for forensic assessment (P = 0.011) and had longer median length of stay (9 vs 5 days, P = 0.0019). CONCLUSION: Almost one third of diagnoses for young patients discharged after an OHCA included neither OHCA nor any underlying cause. Underestimating the burden of OHCA impacts ongoing patient and at-risk family care, data sampling strategies, international statistics and research funding.

Fontan Hepatopathy-Managing Unknowns.

BACKGROUND AND AIMS: How to best monitor Fontan-associated liver disease (FALD) remains unclear. We describe results from a prospective liver care pathway in adults (n=84) with a Fontan circulation. METHODS: Routine assessment of the liver, by acoustic radiation force frequency and ultrasound was undertaken. Results, including liver biochemistry, systemic ventricular function (echocardiography), functional class, medication use and clinical endpoints (varices, hepatocellular carcinoma, heart transplantation and death) were collated. RESULTS: Most individuals returned a cirrhotic range acoustic radiation force impulse imaging (ARFI) result. ARFI values were greater in the proportion of individuals with hepatic nodularity (p=0.024). Univariate analysis demonstrated moderate correlation with platelet number (Spearmans rho= -0.376, p=0.049). Patients with clinical endpoints had lower platelets (p=0.012) but only a trend to hepatic nodularity (p=0.057). Clinical endpoints were more common in those with ventricular dysfunction (p=0.011). Multivariate analysis revealed that age at Fontan and being on angiotensin converting enzyme inhibitors (ACEI) predicted ARFI score (ß=0.06 [95% CI 0.01-0.09], p=0.007 and ß=0.53 [95% CI 0.17-0.89], p=0.005, respectively). However, these associations were not significant once adjusted for Fontan type, age at ARFI, systemic ventricle morphology, ventricle function, or Model for End-stage Liver Disease (MELD-XI) excluding international normalised ratio (INR) (p>0.05 for all). CONCLUSIONS: Ideal FALD monitoring remains unclear. ARFI has utility as a binary non-invasive indicator of cirrhosis, highlighting individuals who may need more frequent ongoing monitoring for hepatocellular carcinoma. However, no definite advantage to serial ARFI, once cirrhotic range ARFI results are present, has been identified.

Prevalence of Multiple Causes of Death Within Young and Middle-Aged People Experiencing Sudden Cardiac Arrest.

BACKGROUND: Multiple causes of death are increasingly reported, particularly in older populations. Rates of multiple causes of young sudden death have not been quantified. METHOD: The End Unexplained Cardiac Death (EndUCD) registry was utilised to identify cases of young sudden death (aged 1-50 years) referred for forensic assessment from April 2019 to April 2022. Causes of death were coded according to whether one or more underlying causes of death were identified. Patients were compared according to the number of causes of death, with significant predictors assessed using logistic regression analysis. RESULTS: 1,085 cases of sudden death were identified. 263 (24.2%) cases had more than one competing cause of their sudden death. The most common multi-causal associations identified were dual non-cardiac causes of the sudden death (n=68), cardiomyopathy with non-cardiac event (n=64) and coronary artery disease with non-cardiac cause (n=63). Multi-causal death was more common in those undergoing comprehensive autopsy examination (95.8% vs 77.6%, p<0.0001), and in the setting of higher body mass index (median 31.3 kg/m2 vs 29.9 kg/m2, p=0.01), older age (44.3 years vs 41.4 years, p<0.0001), non-ventricular cardiac arrest rhythm (93.2% vs 87.3%, p=0.009), and smoking (22.8% vs 14.2%, p=0.001). The strongest predictor of multiple pathologies was comprehensive autopsy examination compared with external inspection, full-body post-mortem computed tomography and review of ancillary documentation and investigations (odds ratio 6.49, 95% confidence interval 3.47-12.14). CONCLUSIONS: One-quarter of young sudden deaths have more than one underlying cause, highlighting the value of comprehensive investigations including autopsy. Awareness of the complexity of young sudden death is important, along with multidisciplinary involvement to ensure all contributors to death are identified.

Causes, circumstances, and potential preventability of cardiac arrest in the young: insights from a state-wide clinical and forensic registry.

AIMS: The causes, circumstances, and preventability of young sudden cardiac arrest remain uncertain. METHODS AND RESULTS: A prospective state-wide multi-source registry identified all out-of-hospital cardiac arrests (OHCAs) in 1-50 year olds in Victoria, Australia, from 2019 to 2021. Cases were adjudicated using hospital and forensic records, clinic assessments and interviews of survivors and family members. For confirmed cardiac causes of OHCA, circumstances and cardiac history were collected. National time-use data was used to contextualize circumstances. 1319 OHCAs were included. 725 (55.0%) cases had a cardiac aetiology of OHCA, with coronary disease (n = 314, 23.8%) the most common pathology. Drug toxicity (n = 226, 17.1%) was the most common non-cardiac cause of OHCA and the second-most common cause overall. OHCAs were most likely to occur in sleep (n = 233, 41.2%). However, when compared to the typical Australian day, OHCAs occurred disproportionately more commonly during exercise (9% of patients vs. 1.3% of typical day, P = 0.018) and less commonly while sedentary (39.6 vs. 54.6%, P = 0.047). 38.2% of patients had known standard modifiable cardiovascular risk factors. 77% of patients with a cardiac cause of OHCA had not reported cardiac symptoms nor been evaluated by a cardiologist prior to their OHCA. CONCLUSION: Approximately half of OHCAs in the young have a cardiac cause, with coronary disease and drug toxicity dominant aetiologies. OHCAs disproportionately occur during exercise. Of patients with cardiac cause of OHCA, almost two-thirds have no standard modifiable cardiovascular risk factors, and more than three-quarters had no prior warning symptoms or interaction with a cardiologist.

The Palliative Approach and Terminal Heart Failure Admissions - Are We Getting it Right?

BACKGROUND: Chronic heart failure has a high mortality and early provision of palliative care supports complex decision-making and improves quality of life. AIM: To explore whether and when a palliative approach was adopted during the last 12 months of life in patients who experienced an in-hospital death from heart failure. DESIGN: Retrospective medical record review of all deaths from chronic heart failure (January 2010 to December 2019). PARTICIPANTS: Admissions with chronic heart failure resulting in death were analysed from an Australian tertiary referral centre. RESULTS: The cohort (n=517) were elderly (median age 83.8 years IQR=77.6-88.7) and male (55.1%). Common comorbidities were ischaemic heart disease (n=293 56.7%) and atrial fibrillation (n=289 55.9%). Life sustaining interventions occurred in 97 (18.8%) patients. In 31 (6.0%) patients referral to specialist palliative care occurred prior to, and in 263 (50.9%) during, the terminal admission. Opioids were prescribed to 440 (85.1%) patients. Comfort care was the documented goal in 158 patients (30.6%). A palliative approach was significantly associated with prior admission in the preceding 12 months (OR=1.5 95% CI=1.0-2.1 p<0.043), receiving outpatient care (OR=2.6 95% CI=1.6-4.1 p<0.01), and admissions in the latter half of the decade (OR=1.5 95% CI=1.0-2.0 p<0.038). CONCLUSION: Despite greater adoption of a palliative approach in the terminal admission over the last decade, a significant proportion of patients receive palliative care late, just prior to death.

Surveillance of End-Organ Damage in Fontan Patients Prior to Transition to Adult Care: Are We There Yet?

BACKGROUND: Recently published guidelines and consensus statements have outlined recommended screening practices for monitoring of end-organ dysfunction in Fontan patients. We reviewed the current approach to end-organ screening in a local population of Fontan patients at the time of transition to adult care. METHODS: Patient data from the Australia and New Zealand Fontan Registry and patient medical records were used to review investigations performed in Fontan patients transitioned from The Royal Children's Hospital Melbourne to an adult centre between 1 July 2015 and 30 June 2020. RESULTS: A total of 32 patients were referred for transition to an adult centre between 1 July 2015 and 30 June 2020 at a mean age of 18.5±0.7 years (12.7±2.5 years post-Fontan). Liver function tests were performed in 22 patients (69%) within 5 years prior to transition and were abnormal in 15 patients (68%). Liver ultrasound was performed in 13 patients (41%) within 5 years prior to the date of transition, of whom 10 (77%) had abnormal findings (features suggestive of hepatic fibrosis in seven [54%], cirrhosis in two [15%], and portal hypertension in three [23%]). Fourteen (14) patients (44%) had no record of a liver ultrasound being performed between the date of the Fontan procedure and the time of transition to adult care. Hepatocellular carcinoma was diagnosed in one patient at 18 months following transition. A total of 24 patients (75%) had a serum creatinine measured within the 5 years prior to transition, and two (8%) had an estimated glomerular filtration rate (eGFR) less than 90 mL/min/1.73 m2. No patient had a urine protein-creatinine ratio measured between the date of the Fontan procedure and the time of transition to adult care. CONCLUSIONS: In this study we have identified that the majority of patients transitioned from a tertiary paediatric centre to an adult centre within the last 5 years did not undergo routine surveillance for end-organ dysfunction. Routine screening for end-organ complications of the Fontan circulation should be incorporated into clinical practice and is an important part of Fontan patient care both pre- and post-transition to adult services.

Higher rates but similar causes of young out-of-hospital cardiac arrest in rural Australian patients.

OBJECTIVE: To determine whether young rural Australians have higher rates or different underlying causes of out-of-hospital cardiac arrest (OHCA). DESIGN: A case-control design identified patients experiencing an OHCA, then compared annual OHCA rates and underlying causes in rural versus metropolitan Victoria. OHCA causes were defined as either cardiac or non-cardiac, with specific aetiologies including coronary disease, cardiomyopathy, unascertained cause of arrest, drug toxicity, respiratory event, neurological event and other cardiac and non-cardiac. For OHCAs with confirmed cardiac aetiology, cardiovascular risk profiles were compared. SETTING: A state-wide prospective OHCA registry (combining ambulance, hospital and forensic data) in the state of Victoria, Australia (population 6.5 million). PARTICIPANTS: Victorians aged 1-50 years old experienced an OHCA between April 2019 and April 2020. MAIN OUTCOME MEASURES: Rates and underlying causes of OHCA in young rural and metropolitan Victorians. RESULTS: Rates of young OHCA were higher in rural areas (OHCA 22.5 per 100 000 rural residents vs. 13.4 per 100 000 metropolitan residents, standardised incidence ratio 168 (95% CI 101-235); confirmed cardiac cause of arrest 12.1 per 100 000 rural residents versus 7.5 per 100 000 metropolitan residents, standardised incidence ratio 161 (95% CI 71-251). The underlying causation of the OHCA and cardiovascular risk factor burden did not differ between rural and metropolitan areas. CONCLUSION: Higher rates of OHCA occur in young rural patients, with standardised incidence ratio of 168 compared to young metropolitan residents. Rural status did not influence causes of cardiac arrest or known cardiovascular risk factor burden in young patients experiencing OHCA.

Management of Maternal Complex Congenital Heart Disease During Pregnancy.

PURPOSE OF THE REVIEW: The purpose of this review is to discuss the risk stratification and management of pregnancy in women with complex congenital heart disease. RECENT FINDINGS: Classifying congenital heart defects (CHD) including both anatomy and physiology is important for maternal risk stratification. Although most women with CHD can tolerate the physiological challenge of pregnancy, some may experience serious risks both to their health and that of their foetus. The WHO maternal risk classification model remains the best-validated risk measure. Ideally, women with CHD should have pre-conception assessment with a CHD cardiologist. General principles of management, such as need for expert centre delivery, a multidisciplinary team, epidural and mode of delivery are based on WHO risk in combination with expert assessment of status. CHD is increasingly prevalent in women of child-bearing age. Assessment by an adult CHD cardiologist, ideally pre-conception, is key in assessing and minimising risk to mother and foetus.

Heart Disease and Pregnancy: The Need for a Twenty-First Century Approach to Care .

Pregnancy and childbirth present a specific challenge to the maternal cardiovascular system. Pre-existing cardiac diseases, or cardiac diseases that occur during pregnancy, are associated with a significant risk of morbidity and mortality for both mother and baby. In recent decades, cardiac disease has emerged as a leading cause of maternal death in most high income countries, including Australia and New Zealand. The burden of cardiac disease in pregnancy is likely to be growing due to an increase in adult survivors with congenital heart disease embarking on pregnancy coupled with demographic shifts in the age and cardiovascular risk factors of women giving birth and the persisting high incidence of acute rheumatic fever in First Nations women. There is widespread consensus that the best obstetric and neonatal outcomes in women with cardiac disease are delivered by a strategy of carefully coordinated multidisciplinary care. Australia and New Zealand currently lack nationally agreed strategies for clinical practice and service delivery for women with heart disease in pregnancy. This state-of-the-art review summarises some of the key issues faced in relation to prevention, diagnosis, treatment and health service delivery in this patient group and concludes with suggested priorities for policy and research.

The End Unexplained Cardiac Death (EndUCD) Registry for Young Australian Sudden Cardiac Arrest.

In 2019, the first multi-source registry of sudden cardiac arrest and death for patients aged 1-50 years launched in Victoria, Australia. Sudden cardiac arrest (SCA) affects approximately fifteen hundred younger Victorians per year. The End Unexplained Cardiac Death (EndUCD) Registry enrols SCA/death (D) cases aged 1-50 years, providing family screening, access to psychological support through clinical sites and creating a genetic biorepository for whole-genome sequencing. The registry will support clear pathways of cardiac assessment, epidemiological profiling and routine family screening and psychological support.

Can post-mortem coronary artery calcium scores aid diagnosis in young sudden death?

This study sought to explore the feasibility and utility of post-mortem coronary artery calcium (CAC) scoring in identifying patients with ischemic heart disease as cause of sudden death. 100 deceased patients aged 18-50 years underwent post-mortem examination in the setting of sudden death. At post-mortem, fifty cases were determined to have ischemic heart disease, and fifty had death attributed to trauma or unascertained causes. The CAC score was calculated in a blinded manner from post-mortem CTs performed on all cases. CAC scores were assessable in 97 non-decomposed cases (feasibility 97%). The median CAC score was 88 Agatston units [IQR 0-286] in patients deceased from ischemic heart disease vs 0 [IQR 0-0] in patients deceased from other causes (p < 0.0001). Presence of any coronary calcification differed significantly between ischemic heart disease and non-ischemic groups (adjusted odds ratio 10.7, 95% CI 3.2-35.5). All cases with a CAC score > 100 (n = 22) had ischemic heart disease as the cause of death. Fifteen cases had a CAC score of zero but severe coronary disease at post-mortem examination. Post-mortem CAC scoring is highly feasible. An elevated CAC score in cases 18-50 years old with sudden death predicts ischemic heart disease at post-mortem examination. However, a CAC score of zero does not exclude significant coronary artery disease. Post-mortem CAC score may be considered as a further assessment tool to help predict likely cause of death when there is an objection to or unavailability of post-mortem examination.

Insights into sudden cardiac death: exploring the potential relevance of non-diagnostic autopsy findings.

AIMS: Unexplained sudden cardiac death (SCD) may be attributable to cardiogenetic disease. Presence or absence of autopsy anomalies detected following premature sudden death direct appropriate clinical evaluation of at-risk relatives towards inherited cardiomyopathies or primary arrhythmia syndromes, respectively. We investigated the relevance of non-diagnostic pathological abnormalities of indeterminate causality (uncertain) such as myocardial hypertrophy, fibrosis, or inflammatory infiltrates to SCD. METHODS AND RESULTS: At-risk relatives of unexplained SCD cases aged 1-64 years without prior cardiac disease (n = 98) with either normal and negative (40%, true sudden arrhythmic death syndrome; SADS) or isolated non-diagnostic (60%, uncertain sudden unexplained death; SUD) cardiac histological autopsy findings at a central forensic pathology unit were referred to the regional unexplained SCD clinic for clinical cardiac phenotyping. Uncertain SUD were older than true SADS cases (31.8 years vs. 21.1 years, P < 0.001). A cardiogenetic diagnosis was established in 24 families (24.5%) following investigation of 346 referred relatives. The proportions of uncertain SUD and true SADS explained by familial cardiogenetic diagnoses were similar (20% vs. 31%, P = 0.34, respectively), with primary arrhythmia syndromes predominating. Unexplained SCD cases were more likely than matched non-cardiac premature death controls to demonstrate at least one uncertain autopsy finding (P < 0.001). CONCLUSION: Primary arrhythmia syndromes predominate as familial cardiogenetic diagnoses amongst both uncertain SUD and true SADS cases. Non-diagnostic or uncertain histological findings associate with SUD, though cannot be attributed a causative status. At-risk relatives of uncertain SUD cases should be evaluated for phenotypic evidence of both ion channel disorders and cardiomyopathies.

Familial Aortopathies - State of the Art Review.

Aortopathies are conditions that result in aortic dilatation, aneurysm formation and dissection. Familial aortopathies (perhaps better known as heritable thoracic aortic aneurysm and dissection, h-TAAD, as not all have a positive family history) are recognised to have an underlying genetic cause and affect the aorta, predisposing it to the above pathologies. These conditions can also affect the extra-aortic vasculature, particularly large elastic arteries and other body systems. Mutations in a number of genes have been associated with h-TAAD. However, not all affected families have a pathogenic gene variant identified-highlighting the importance of a three-generational family history and the likely role of both environmental factors and future gene discoveries in furthering knowledge. Survival has improved over the last few decades, essentially due to surgical intervention. The benefit of identifying affected individuals depends upon a regular surveillance program and timely referral for surgery before complications such as dissection. Further research is required to appreciate fully the effects of individual gene variants and improve evidence for prophylactic medical therapy, as well as to understand the effect of h-TAAD on quality of life and life choices, particularly around exercise and pregnancy, for affected individuals. This will be complemented by laboratory-based research that seeks to understand the tissue pathways that underlie development of arterial pathology, ideally providing targets for novel medical therapies and a means of non-invasively identifying individuals at increased vascular risk to reduce dissection, which remains a devastating life-threatening event.

Pregnancy Outcomes in Women After the Arterial Switch Operation.

BACKGROUND: Pregnancy outcomes after the arterial switch operation (ASO) are rare. We sought to determine outcomes of ASO survivors who underwent pregnancy. METHODS: Female patients who had an ASO and underwent pregnancy were identified from the congenital heart disease pregnancy clinic at The Royal Melbourne Hospital. All follow-up data were collected retrospectively by medical record review. RESULTS: Eleven (11) women were identified as having undergone medical care during pregnancy, from the adult congenital database, at The Royal Melbourne Hospital. There were 17 successful pregnancies, and nine women have been followed post pregnancy. Of the 17 successful deliveries, eight were delivered by Caesarean section, seven were vaginal deliveries and two were instrumented vaginal deliveries. Of the eight Caesarean sections, five were emergency and three were elective. The indications for emergency Caesarean section were obstructed labour (n = 2), abnormal cardiotocography (n = 1), obstructed labour and abnormal cardiotocography (n = 1) and congestive cardiac failure (n = 1). There was one neonatal complication (respiratory distress requiring intubation) in a child born at 31 weeks. There were maternal obstetric complications in 10 patients. There were two maternal cardiac complications during pregnancy (heart failure and rapid atrial fibrillation/flutter). There was no change in left ventricular function post-pregnancy. There was progression of severity of neo-aortic valve regurgitation in two patients post pregnancy (trivial to mild and moderate-severe to severe respectively). CONCLUSION: Pregnancy post ASO appears to be safe in the majority of women. Maternal cardiac complications are uncommon in patients without residual significant haemodynamic lesions, although maternal obstetric complications may be common.

Familial Dilated Cardiomyopathy.

Advances in human genome sequencing have re-invigorated genetics studies of dilated cardiomyopathy (DCM), facilitating genetic testing and clinical applications. With a range of genetic testing options now available, new challenges arise for data interpretation and identifying single pathogenic variants from the many thousands of rare variants present in every individual. There is accumulating evidence that genetic factors have an important role in the pathogenesis of DCM. However, although more than 100 genes have been implicated to date, the sensitivity of genetic testing, even in familial disease, is only ∼25-40%. As more patients are genotyped, nuanced information about disease phenotypes is emerging including variability in age of onset and penetrance of DCM, as well as additional cardiac and extra-cardiac features. Genotype-phenotype correlations have also identified a subset of genes that can be highly arrhythmogenic or show frequent progression to heart failure. Recognition of variants in these genes is important as this may impact on the timing of implantable cardioverter-defibrillators or heart transplantation. Finding a causative variant in a patient with DCM allows predictive testing of family members and provides an opportunity for preventative intervention. Diagnostic imaging modalities such as speckle-tracking echocardiography and cardiac magnetic resonance imaging are increasingly being used to detect and monitor pre-clinical ventricular dysfunction in asymptomatic variant carriers. Although there are several examples of successful genotype-based therapy, optimal strategies for implementation of precision medicine in familial DCM remain to be determined. Identification of modifiable co-morbidities and lifestyle factors that exacerbate or protect against DCM development in genetically-predisposed individuals remains a key component of family management.