Depression and poor outcome after an acute coronary event: Clarification of risk periods and mechanisms.

OBJECTIVE: Lifetime depression and depression around the time of an acute coronary syndrome event have been associated with poor cardiac outcomes. Our study sought to examine the persistence of this association, especially given modern cardiac medicine's successes. METHODS: For 332 patients admitted for an acute coronary syndrome, a baseline interview assessed major depression status, and psychological measures were administered. At 1 and 12 months post-acute coronary syndrome event, telephone interviews collected rates of hospital readmission and/or death and major depression status, while biomarker information was examined using medical records. RESULTS: The 12-month mortality rate was 2.3% and cardiac readmission rate 21.0%. Depression subsequent to an acute coronary syndrome event resulted in a threefold and 2.5-fold increase in 1-month and 12-month odds of cardiac readmission or death, respectively. No relationship with past depressive episodes was found. Poor sleep was associated with higher trait anxiety and neuroticism scores and with more severe depression. CONCLUSION: Lifetime depression may increase the risk of depression around the time of an acute coronary syndrome but not influence cardiac outcomes. We suggest that poor sleep quality may be causal or indicate high anxiety/neuroticism, which increases risk to depression and contributes to poor cardiac outcomes rather than depression being the primary causal factor.

Medical Management of Rheumatic Heart Disease: A Systematic Review of the Evidence.

Rheumatic heart disease (RHD) is an important cause of heart disease globally. Its management can encompass medical and procedural (catheter and surgical) interventions. Literature pertaining to the medical management of RHD from PubMed 1990-2016 and via selected article reference lists was reviewed. Areas included symptom management, left ventricular dysfunction, rate control in mitral stenosis, atrial fibrillation, anticoagulation, infective endocarditis prophylaxis, and management in pregnancy. Diuretics, angiotensin blockade and beta-blockers for left ventricular dysfunction, and beta-blockers and If inhibitors for rate control in mitral stenosis reduced symptoms and improved left ventricular function, but did not alter disease progression. Rhythm control for atrial fibrillation was preferred, and where this was not possible, rate control with beta-blockers was recommended. Anticoagulation was indicated where there was a history of cardioembolism, atrial fibrillation, spontaneous left atrial contrast, and mechanical prosthetic valves. While warfarin remained the agent of choice for mechanical valve implantation, non-vitamin K antagonist oral anticoagulants may have a role in RHD-related AF, particularly with valvular regurgitation. Evidence for anticoagulation after bioprosthetic valve implantation or mitral valve repair was limited. RHD patients are at increased risk of endocarditis, but the evidence supporting antibiotic prophylaxis before procedures that may induce bacteremia is limited and recommendations vary. The management of RHD in pregnancy presents particular challenges, especially regarding decompensation of previously stable disease, the choice of anticoagulation, and the safety of medications in both pregnancy and breast feeding.

Cardiac care for Indigenous Australians: practical considerations from a clinical perspective.

Indigenous Australians have a much high burden of cardiovascular disease, which occurs at an earlier age than in the non-Indigenous population. Comorbidities such as diabetes are common. Early diagnosis of ischaemic heart disease may be difficult because of barriers such as distance to medical centres, communication problems and family and cultural responsibilities. Disparities in cardiac care between Indigenous and non-Indigenous populations are well documented, with examples including reduced angiography and revascularisation rates in Indigenous patients. Indigenous patients can have poor health literacy and need careful explanation of procedures, with the assistance of Aboriginal health workers, visual aids and family members. Acute rheumatic fever and chronic rheumatic heart disease remain ongoing health problems in Indigenous communities, especially in remote areas. Ambulatory care of Indigenous Australians with chronic cardiovascular disease is challenging. It requires well supported health care systems, including Aboriginal health workers and cardiac nurse coordinators to case-manage patients. A holistic approach to care, with attention directed towards both cardiac and non-cardiac comorbidities, is crucial for optimal management of cardiovascular disease in Indigenous Australians. Multidisciplinary care, involving an empowered and supported primary care team working together with specialists through outreach services or telehealth, is important for patients who are at high clinical risk and those living in remote areas. Indigenous Australians deserve the same level of evidence-based cardiovascular health care and access to care as non-Indigenous Australians.

Outcome following valve surgery in Australia: development of an enhanced database module.

BACKGROUND: Valvular heart disease, including rheumatic heart disease (RHD), is an important cause of heart disease globally. Management of advanced disease can include surgery and other interventions to repair or replace affected valves. This article summarises the methodology of a study that will incorporate enhanced data collection systems to provide additional insights into treatment choice and outcome for advanced valvular disease including that due to RHD. METHODS: An enhanced data collection system will be developed linking an existing Australian cardiac surgery registry to more detailed baseline co-morbidity, medication, echocardiographic and hospital separation data to identify predictors of morbidity and mortality outcome following valve surgery. DISCUSSION: This project aims to collect and incorporate more detailed information regarding pre and postoperative factors and subsequent morbidity. We will use this to provide additional insights into treatment choice and outcome.

Outcomes after mitral valve surgery for rheumatic heart disease.

OBJECTIVE: To further the understanding of the factors influencing outcome following rheumatic heart disease (RHD) related mitral valve surgery, which globally remains an important cause of heart disease and a particular problem in Indigenous Australians. METHODS: The Australian Cardiac Surgery Database was utilised to assess outcomes following mitral valve repair and replacement for RHD and non-RHD valve disease. The association with aetiology, demographics, comorbidities, preoperative status and operative procedure was evaluated. RESULTS: Mitral valve repairs and replacements undertaken in Australia were analysed from 119 and 1078 RHD surgical procedures and 3279 and 2400 non-RHD procedures, respectively. RHD mitral valve repair, compared with replacement, resulted in a slightly shorter hospital stay and more reoperation for valve dysfunction, but no difference in 30-day survival. In unadjusted survival analysis to 5 years, RHD mitral valve repair and replacement were no different (HR 0.86, 95% CI 0.4 to 1.7), non-RHD repair was superior to replacement (HR 1.7, 95% CI 1.4 to 2.0), RHD and non-RHD repair were no different (HR 0.9, 95% CI 0.5 to 1.7), and RHD replacement was superior to non-RHD (HR 1.5, 95% CI 1.2 to 1.9). None of these differences persisted in adjusted analyses and there was no difference in long-term survival for Indigenous Australians. CONCLUSION: In this large prospective cohort study we have demonstrated that adjusted long-term survival following RHD mitral valve repair surgery in Australia is no different to replacement and no different to non-RHD. Interpretation of valve surgery outcome requires careful consideration of patient factors that may also influence survival.

The burden and implications of preoperative atrial fibrillation in Australian heart valve surgery patients.

BACKGROUND: Atrial fibrillation (AF) is the most common preoperative arrhythmia in heart valve surgery patients and its prevalence is rising. This study aims to investigate the impact of AF on valve surgery early complications and survival and on valve disease of different aetiologies and populations with particular reference to Indigenous Australians with rheumatic heart disease (RHD). METHODS: The Australian and New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database was analysed to determine the association between preoperative AF and valve surgery outcome. Its association with demographics, co-morbidities, preoperative status and short and long term outcome was assessed. RESULTS: Outcome of 1594 RHD and 19,029 non-RHD-related surgical procedures was analysed. Patients with preoperative AF were more likely to be older, female, Indigenous, to have RHD and to bear a greater burden of comorbidities. Patients with RHD and preoperative AF had a longer hospital stay and were more likely to require reoperation. Adjusted short (OR 1.4, 95% CI 1.2-1.7) and long term (HR 1.5, 95% CI 1.3-1.7) survival was inferior for patients with non-RHD preoperative AF but was no different for Indigenous and non-Indigenous Australians with RHD. CONCLUSIONS: In this prospective Australian study, patients with valve disease and preoperative AF had inferior short and long term survival. This was particularly the case for patients with non-RHD valve disease. Earlier intervention or more aggressive AF management should be investigated as mechanisms for enhancing postoperative outcomes. This may influence treatment choice and the need for ongoing anticoagulation.

Case load and valve surgery outcome in Australia.

BACKGROUND: In Australia it has been suggested that heart valve surgery, particularly for rheumatic heart disease (RHD), should be consolidated in higher volume centres. International studies of cardiac surgery suggest large volume centres have superior outcomes. However the effect of site and surgeon case load on longer term outcomes for valve surgery has not been investigated. METHODS: The Australian and New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database was analysed. The adjusted association between both average annual site and surgeon case load on short term complications and short and long-term survival was determined. RESULTS: Outcomes associated with 20,116 valve procedures at 25 surgical sites and by 93 surgeons were analysed. Overall adjusted analysis showed increasing site and surgeon case load was associated with longer ventilation, less reoperation and more anticoagulant complications. Increasing surgeon case load was also associated with less acute kidney injury. Adjusted 30-day mortality was not associated with site or surgeon case load. There was no consistent relationship between increasing site case load and long term survival. The association between surgeon case load and outcome demonstrated poorer adjusted survival in the highest volume surgeon group. CONCLUSIONS: In this Australian study, the adjusted association between surgeon and site case load was not simple or consistent. Overall larger volume sites or surgeons did not have superior outcomes. Mandating a particular site case load level for valve surgery or a minimum number of procedures for individual surgeons, in an Australian context, cannot be supported by these findings.

One-step extraction and quantitation of toxic alcohols and ethylene glycol in plasma by capillary gas chromatography (GC) with flame ionization detection (FID).

OBJECTIVES: Clinical analysis of volatile alcohols (i.e. methanol, ethanol, isopropanol, and metabolite acetone) and ethylene glycol (EG) generally employs separate gas chromatography (GC) methods for analysis. Here, a method for combined analysis of volatile alcohols and EG is described. DESIGN AND METHODS: Volatile alcohols and EG were extracted with 2:1 (v:v) acetonitrile containing internal standards (IS) 1,2 butanediol (for EG) and n-propanol (for alcohols). Samples were analyzed on an Agilent 6890 GC FID. The method was evaluated for precision, accuracy, reproducibility, linearity, selectivity and limit of quantitation (LOQ), followed by correlation to existing GC methods using patient samples, Bio-Rad QC, and in-house prepared QC material. RESULTS: Inter-day precision was from 6.5-11.3% CV, and linearity was verified from down to 0.6mmol/L up to 150mmol/L for each analyte. The method showed good recovery (~100%) and the LOQ was calculated to be between 0.25 and 0.44mmol/L. Patient correlation against current GC methods showed good agreement (slopes from 1.03-1.12, and y-intercepts from 0 to 0.85mmol/L; R(2)>0.98; N=35). Carryover was negligible for volatile alcohols in the measuring range, and of the potential interferences tested, only toluene and 1,3 propanediol interfered. The method was able to resolve 2,3 butanediol, diethylene glycol, and propylene glycol in addition to the peaks quantified. CONCLUSIONS: Here we describe a simple procedure for simultaneous analysis of EG and volatile alcohols that comes at low cost and with a simple liquid-liquid extraction requiring no derivitization to obtain adequate sensitivity for clinical specimens.

A review of outcome following valve surgery for rheumatic heart disease in Australia.

BACKGROUND: Globally, rheumatic heart disease (RHD) remains an important cause of heart disease. In Australia it particularly affects younger Indigenous and older non-Indigenous Australians. Despite its impact there is limited understanding of the factors influencing outcome following surgery for RHD. METHODS: The Australian and New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database was analysed to assess outcomes following surgical procedures for RHD and non-RHD valvular disease. The association with demographics, co-morbidities, pre-operative status, valve(s) affected and operative procedure was evaluated. RESULTS: Outcome of 1384 RHD and 15843 non-RHD valve procedures was analysed. RHD patients had longer ventilation, experienced fewer strokes and had more readmissions to hospital and anticoagulant complications. Mortality following RHD surgery at 30 days was 3.1% (95% CI 2.2 - 4.3), 5 years 15.3% (11.7 - 19.5) and 10 years 25.0% (10.7 - 44.9). Mortality following non-RHD surgery at 30 days was 4.3% (95% CI 3.9 - 4.6), 5 years 17.6% (16.4 - 18.9) and 10 years 39.4% (33.0 - 46.1). Factors independently associated with poorer longer term survival following RHD surgery included older age (OR1.03/additional year, 95% CI 1.01 - 1.05), concomitant diabetes (OR 1.7, 95% CI 1.1 - 2.5) and chronic kidney disease (1.9, 1.2 - 2.9), longer invasive ventilation time (OR 1.7 if greater than median value, 1.1- 2.9) and prolonged stay in hospital (1.02/additional day, 1.01 - 1.03). Survival in Indigenous Australians was comparable to that seen in non-Indigenous Australians. CONCLUSION: In a large prospective cohort study we have demonstrated survival following RHD valve surgery in Australia is comparable to earlier studies. Patients with diabetes and chronic kidney disease, were at particular risk of poorer long-term survival. Unlike earlier studies we did not find pre-existing atrial fibrillation, being an Indigenous Australian or the nature of the underlying valve lesion were independent predictors of survival.

A review of valve surgery for rheumatic heart disease in Australia.

BACKGROUND: Globally, rheumatic heart disease (RHD) remains an important cause of heart disease. In Australia it particularly affects older non-Indigenous Australians and Aboriginal Australians and/or Torres Strait Islander peoples. Factors associated with the choice of treatment for advanced RHD remain variable and poorly understood. METHODS: The Australian and New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database was analysed. Demographics, co-morbidities, pre-operative status and valve(s) affected were collated and associations with management assessed. RESULTS: Surgical management of 1384 RHD and 15843 non-RHD valve procedures was analysed. RHD patients were younger, more likely to be female and Indigenous Australian, to have atrial fibrillation (AF) and previous percutaneous balloon valvuloplasty (PBV). Surgery was performed on one valve in 64.5%, two valves in 30.0% and three valves in 5.5%. Factors associated with receipt of mechanical valves in RHD were AF (OR 2.69) and previous PBV (OR 1.98) and valve surgery (OR 3.12). Predictors of valve repair included being Indigenous (OR 3.84) and having fewer valves requiring surgery (OR 0.10). Overall there was a significant increase in the use of mitral bioprosthetic valves over time. CONCLUSIONS: RHD valve surgery is more common in young, female and Indigenous patients. The use of bioprosthetic valves in RHD is increasing. Given many patients are female and younger, the choice of valve surgery and need for anticoagulation has implications for future management of RHD and related morbidity, pregnancy and lifestyle plans.

A framework for overcoming disparities in management of acute coronary syndromes in the Australian Aboriginal and Torres Strait Islander population. A consensus statement from the National Heart Foundation of Australia.

Aboriginal and Torres Strait Islander patients with acute coronary syndromes (ACS) experience lower intervention rates and poorer outcomes compared with non-Indigenous patients. A broad range of geographical, cultural and systemic factors contribute to delays and suboptimal treatment for ACS. Every Indigenous ACS patient, regardless of where they live, should be able to expect a coordinated, patient-centred pathway of care provided by designated provider clinical networks and supported by Indigenous cardiac coordinators, Aboriginal liaison officers (ALOs) and health workers. These designated provider clinical networks provide: appropriate prehospital and inhospital treatment an individualised patient care plan developed jointly with the patient and his or her family culturally appropriate education initiated within the hospital setting and involving families with support from ALOs effective follow-up care and access to relevant secondary prevention programs. We outline generic pathways to provide policymakers, health planners and health care providers with a framework for ACS diagnosis and management that can be implemented across the diverse settings in which Aboriginal and Torres Strait Islander people reside and their care is delivered, in order to optimise care and assertively address the current disparities in outcomes.

Analytical measurement of serum 25-OH-vitamin D3, 25-OH-vitamin D2 and their C3-epimers by LC-MS/MS in infant and pediatric specimens.

OBJECTIVES: To develop a simple and sensitive LC-MS/MS procedure for quantification of serum 25-OH-vitamin D3 (25-OH-D3), 25-OH-vitamin D2 (25-OH-D2), and their C3-epimers. METHODS: Serum 25-OH-vitamin D metabolites were extracted with MTBE and quantified by LC-MS/MS. Commercially available calibrators and QC materials were employed. The ion-transition 401.2→365.2 was monitored for 25-OH-D3 and C3-epi-25-OH-D3, 407.2→371.3 for d6-25-OH-D3, 413.2→331.2 for 25-OH-D2 and C3-epi-25-OH-D2 and 419.2→337.1 for, d6-25-OH-D2. As a proof-of-principle, 25-OH-D3 and C3-epi-25-OH-D3 were quantified in 200 pediatric subjects (0-20 years of age). Cholecalciferol supplements were examined as a potential source of C3-epimer. RESULTS: The assay provided an LLOQ of ≤2.8 nmol/L for all 25-OH-D metabolites, with a linear response up to 400 nmol/L. The CV was <10% for 25-OH-D2/3 and <15% for C3-epi-25-OH-D3. C3-epi-25-OH-D3 was quantified in all subjects, with higher concentrations observed in infants ≤1 year of age (11.44 nmol/L vs. 4.4 nmol/L; p<0.001). Within the first year of life, 25-OH-D3 concentrations increased linearly, while C3-epi-25-OH-D3 concentrations remained constant. At 12 months of age, C3-epi-25-OH-D3 concentration dropped by almost 50% (11.4 nmol/L in infants ≤1year of age vs. 5.4 nmol/L in infants 1-2years of age; p<0.001). Liquid vitamin D3 supplements did not contain appreciable amounts of C3-epi-D3. CONCLUSIONS: The proposed LC-MS/MS procedure is suitable for quantifying 25-OH-D3 metabolites. Although the C3-epimer is present in all pediatric subjects, it is significantly elevated in individuals ≤1 year of age and drops at 12 months of age. Oral vitamin D supplements are unlikely to be a significant source of C3-vitamin D epimer.

GAD is good? Generalized anxiety disorder predicts a superior five-year outcome following an acute coronary syndrome.

While differing anxiety disorders have been reported to have quite variable impact on outcome following an acute coronary syndrome (ACS), a recent study quantified generalized anxiety disorder (GAD) as having a distinctly negative impact. We examined anxiety disorder status at baseline for any differential five-year impact on cardiac outcome following initial hospitalization for an ACS in 489 subjects. Of those initially assessed, 89% were examined at a five-year review. There were non-significant trends for all non-GAD anxiety disorders to be associated with a worse cardiac outcome. Meeting GAD criteria (both at baseline assessment and over the subjects' lifetime) was associated with a superior five-year cardiac outcome, particularly in the sub-set of those experiencing GAD as their only anxiety disorder, and after controlling for depression and medical comorbidities. As our results are at distinct variance with two previous studies specifically examining the impact of GAD on outcome in cardiac patients, we consider methodological and other explanations. We conclude that, if our findings are valid, then they may more reflect GAD patients having a 'constructive worrying' capacity and therefore being more likely to seek help in response to less severe somatic symptoms and to also be more adherent with cardiac rehabilitation programs.

Specificity of depression following an acute coronary syndrome to an adverse outcome extends over five years.

Many studies have demonstrated that depression is associated with a worse cardiovascular outcome and increased risk of death in those experiencing an acute coronary syndrome (ACS). Recent studies have suggested, however, that any association is strongly influenced by the timing of the depression, with post-ACS depression providing the greatest risk. Establishing any timing impact should assist etiological clarification. We initially recruited 489 subjects hospitalized for an ACS, assessed lifetime and current depression, and then - at 1 and 12 months - assessed subsequent depression. Subjects were followed for up to 5 years to assess cardiovascular outcome and the impact of depression at differing time points, with three defined poor outcome categories (i.e. cardiac admission and/or cardiac rehospitalization). While outcome was associated with a number of non-depression variables, a poor outcome was most clearly associated with depressive episodes emerging at the time of the ACS but with some risk affected by episodes that commenced prior to the ACS and being persistent. Neither lifetime depressive episodes nor transient depressive episodes occurring around the baseline ACS event appeared to provide any risk. Study findings indicate that any differential deleterious impact of post-ACS depression has both short-term and longer-term outcomes, and, by implicating the centrality of post-ACS depression, should assist studies seeking to identify causal explanations.

Pediatric reference intervals for lymphocyte vitamin C (ascorbic acid).

OBJECTIVE: To establish pediatric reference intervals for lymphocyte vitamin C. DESIGN AND METHODS: This was a prospective study of 194 well children aged 0-7 years old of mixed ethnicity who had blood drawn for the purpose of this study. Blood was collected during elective surgery under general anesthesia and lymphocytes isolated and stored as frozen ascorbic acid lymphocyte lysates for later HPLC analysis by previously described methodology. Reference intervals were established according to the Clinical and Laboratory Standards Institute (CLSI) and the International Federation of Clinical Chemistry (IFCC) guidelines (C28-A3). Horn-Pesce robust method was used to estimate the 95% confidence interval and 95% reference interval. RESULTS: Reference intervals were independent of age or gender and shown to be 12.9-52.8 µg/10(8) cells (lymphocytes). CONCLUSION: We have defined pediatric reference ranges for lymphocyte vitamin C in healthy, fasted children at a relevant age group (0-7 years). The new reference interval can now be used to more reliably explore possible implications of variation of vitamin C levels on bleeding and other clinical signs.