Off- vs. On-Pump Coronary Artery Bypass Grafting Long-Term Survival is Driven by Incompleteness of Revascularisation.

BACKGROUND: Off-pump coronary artery bypass grafting (CABG) negates the requirement for extracorporeal circulation used with the traditional on-pump approach. However, off-pump CABG is technically more challenging and may theoretically lead to less complete revascularisation. Recent data suggests a prognostic benefit for traditional on-pump CABG, but the mechanism for this remains unclear. We hypothesised that the inferior outcomes with off-pump CABG could be driven by the need for repeat revascularisation, with this benefit only becoming clear at long-term follow-up. We therefore evaluated short, medium and long-term outcomes of patients undergoing revascularisation with on vs. off-pump CABG. METHODS: Electronic databases were searched to identify suitable randomised controlled trials enrolling ≥100 patients in each arm. Clinical outcomes were extracted at 30-days, 12-months or >4years. The primary outcome was long-term all-cause death, while secondary outcomes included 30-day, 12-month and >4-year cardiac death, stroke, myocardial infarction or revascularisation. RESULTS: Thirteen (13) studies comprising 13,234 patients were included. Off-pump CABG was associated with an increased risk of all-cause death (Odds Ratio [OR] 1.18, 95% confidence interval [CI] 1.02-1.32, p=0.01) and repeat bypass surgery (OR 2.57, 95%CI 1.23-5.39, p=0.01) at long-term follow-up. A significant, increased requirement for revascularisation in off-pump was seen at 12-month follow-up (OR 1.59, 95%CI 1.09-2.33, p=0.02). No differences were noted between groups at 30-days, 12-months and >4years for myocardial infarction or stroke. CONCLUSIONS: Off-pump CABG is associated with significantly higher rates of all-cause mortality rate at long-term follow-up. These outcomes demonstrate a temporal relationship that may be driven by a greater requirement for repeat revascularisation at 1- and 5-year follow-up. STUDY REGISTRATION: CRD42018102019 (PROSPERO).

Adult and Paediatric Cardiac Intervention in Timor-Leste: Disease Burden, Demographics and Clinical Outcomes.

BACKGROUND: The East Timor Hearts Fund (ETHF) is a charitable organisation of Australian cardiologists providing outreach screening in Timor-Leste. For patients requiring intervention, ETHF arranges logistics, procedures, and postoperative care. The aim of this project is to evaluate outcomes of patients requiring intervention. METHODS: The ETHF database of all patients was utilised to identify patients with disease warranting surgical or percutaneous intervention. Both patients who underwent intervention and those who did not proceed to intervention were included in this study. Patients who had intervention arranged by other organisations but have then had follow-up with ETHF were also included. Overall demographics and pre and postoperative factors were assessed, with sub-group analysis of adult and paediatric patients to identify any differences in care. RESULTS: Of 221 patients requiring intervention, 101 patients underwent intervention, receiving 22 different operations or procedures. Patients were predominantly young (median age 17.5 years) and female (64.7%), with rheumatic heart disease (63.8%). Twenty-four (24) (33.3%) women aged 15-45 years old with cardiac disease warranting intervention were documented as pregnant or breastfeeding at time of clinic assessment. Of patients who did not proceed to intervention, adults were more likely to be lost to follow-up (42.4% vs 18.5%) while paediatric patients were more likely to experience progression of disease (18.5% vs 7.5%, p=0.005). Median waitlist time was 5 months, with no significant difference between adults and children, correlating with a preoperative mortality rate of 5.4%. For patients who underwent intervention, post-procedure mortality was extremely low (0.9%) and attendance of at least one post-procedure review was excellent (99.0%). Eleven (11) (10.9%) patients have required repeat intervention, with no difference in rates between adult and paediatric patients. Length of follow-up extends up to 20 years for some patients. CONCLUSION: The Timor-Leste interventional cohort was predominantly a young female population with rheumatic and congenital cardiac disease. There were also high rates of pregnancy amongst female patients with severe cardiac disease. Delayed access to intervention may result in preoperative adverse events and mortality, and is a key target for improvement. Patients who undergo intervention have very low post-procedural mortality, good adherence to early medical follow-up and good long-term outcomes.

Variation in coronary angiography rates in Australia: correlations with socio-demographic, health service and disease burden indices.

BACKGROUND: Variation in the provision of coronary angiography is associated with health care inefficiency and inequity. We explored geographic, socio-economic, health service and disease indicators associated with variation in angiography rates across Australia. METHODS: Australian census and National Health Survey data were used to determine socio-economic, health workforce and service indicators. Hospital separations and coronary deaths during 2011 were identified in the National Hospital Morbidity and Mortality databases. All 61 Medicare Locals responsible for primary care were included, and age- and sex-standardised rates of acute coronary syndrome (ACS) incidence, coronary angiography, revascularisation and mortality were tested for correlations, and adjusted by Bayesian regression. RESULTS: There were 3.7-fold and 2.3-fold differences between individual Medicare Locals in the lowest and highest ACS and coronary artery disease mortality rates respectively, whereas angiography rates varied 5.3-fold. ACS and death rates within Medicare Locals were correlated (partial correlation coefficient [CC], 0.52; P < 0.001). There was modest correlation between ACS and angiography rates (CC, 0.31; P = 0.018). The proportion of patients undergoing angiography who proceeded to revascularisation was inversely correlated with the total angiogram rate (CC, -0.71; P < 0.001). Socio-economic disadvantage and remoteness were correlated with disease burden, ACS incidence and mortality, but not with angiography rate. In the adjusted analysis, the strongest association with local angiography rates was with admissions to private hospitals (71 additional angiograms [95% CI, 47-93] for every 1000 admissions). CONCLUSION: Variation in rates of coronary angiography, not related to clinical need, occurs across Australia. A greater focus on clinical care standards and better distribution of health services will be required if these variations are to be attenuated.

How changes to the Medicare Benefits Schedule could improve the practice of cardiology and save taxpayer money.

Rising health care costs above inflation are placing serious strains on the sustainability of the Australian Medicare system in its current structure. The Medicare Benefits Schedule (MBS), which lists rebates payable to patients for private medical services provided on a fee-for-service basis, is the cornerstone of the Australian health care system. Introduced in the 1980s, the MBS has changed little despite major advances in the evidence base for the practice of cardiology. We outline how we believe sensible changes to the MBS listings for four cardiac services--invasive coronary angiography, computed tomography coronary angiography, stress testing and percutaneous coronary intervention--would improve the clinical practice of cardiology and save substantial amounts of taxpayer money.

Transcatheter closure of secundum atrial septal defects: results in patients with large and extreme defects.

BACKGROUND: Transcatheter closure of moderate sized atrial septal defects (ASD) has been demonstrated to be safe and effective. However, the feasibility of transcatheter closure of very large defects is less clear, particularly when an aortic rim of septal tissue is absent. METHODS: The study included patients referred for transcatheter ASD closure with maximal ASD diameter ≥ 20 mm at pre-procedural transoesophageal echocardiography. Patients were grouped according to presence of moderately large (20-29 mm), very large (30-39 mm), or extremely large (≥ 40 mm) ASD size. Procedural success was defined by successful device deployment and absence of complications. RESULTS: Forty-two patients (median age 40 years, range 12-85 years, 76% female) were included in the study. The mean maximal ASD diameter was 29.0 ± 7.4mm. Twenty-three patients had moderately large ASDs (23.0 ± 2.8mm); 13 had very large ASDs (33.1 ± 2.9 mm) and six had extremely large ASDs (41.3 ± 1.6 mm). The aortic rim was absent in 22 patients, and present in 20 patients (4.7 ± 2.9 mm). Transcatheter defect closure was successful in 36 of 42 patients (86%). Procedural success was 100% in the moderately large ASD group, 92% in the very large group but only 17% (one out of six) in the extremely large group. If patients with ASD ≥ 40 mm were excluded (n = 6), the overall success rate was 97%. A single complication (device dislodgement) occurred in a patient with a 42 mm defect and a deficient postero-inferior rim. The presence or absence of an aortic rim of septum did not influence procedural success. CONCLUSION: The vast majority (97%) of large ASDs in the range 20-39 mm can be successfully closed percutaneously with a low or zero complication rate. However, procedural success is poor when attempting closure of extreme defects (≥ 40 mm), regardless of whether an aortic rim of septal tissue or present or absent.

Multi-modality guided trans-apical closure of recurrent mitral para-valvular regurgitation after failed surgical management in a patient with osteogenesis imperfecta.

We report a case of a 54 year-old man with osteogenesis imperfecta who developed severe para-valvular mitral regurgitation after a second heart operation to correct the same problem. The large para-valvular leak was successfully closed with an Amplatzer Vascular Plug III delivered from the apical approach.

A new algorithm for the management of stable coronary artery disease incorporating CT coronary angiography and fractional flow reserve: how we can improve outcomes and reduce costs.

Computed tomography coronary angiography is the most reliable diagnostic test for coronary atherosclerosis. Stress testing should be reserved for diagnosis of myocardial ischaemia. Revascularisation, either by stenting or bypass grafts, is commonly performed in patients with stable coronary artery disease but is a double-edged sword. In the presence of ischaemia, revascularisation improves outcomes; in its absence, outcomes are worsened. In current practice, the decision of whether to revascularise is mainly made on the basis of the angiographic appearance of the coronary lesion in question. Physiological assessment of coronary lesions by the use of a pressure wire and measurement of fractional flow reserve (FFR) often shows that lesions thought to be sufficiently severe to warrant stenting or bypass do not cause ischaemia. A recent randomised study has shown that using FFR measurements to guide coronary stenting resulted in a lower use of stents, decreased costs and superior outcomes at 2 years, compared with traditional angiographic assessment alone. We believe that changes to the methods of health reimbursement are needed in both the public and private health systems, to facilitate greater use of FFR measurement.

Exercise-induced right ventricular dysplasia/cardiomyopathy--an emerging condition distinct from arrhythmogenic right ventricular dysplasia/cardiomyopathy.

We report a case of a 32-year-old female world champion triathlete who developed exercise induced recurrent ventricular tachycardia (VT). Investigations supported a diagnosis of the newly recognised condition "exercise induced right ventricular dysplasia/cardiomyopathy" (EIRVD/C). The VT could be easily terminated by burst pacing from the RV apex and the athlete has been successfully treated with an internal cardioverter defibrillator (ICD).

Profound hypoxaemia corrected by PFO closure device in carcinoid heart disease.

A 66-year-old man with known metastatic carcinoid tumor presented with increasing dyspnoea, right heart failure and marked hypoxaemia which did not correct with oxygen. Echocardiography demonstrated severe tricuspid regurgitation, moderate pulmonary regurgitation and marked right heart dilatation. The inter-atrial septum was aneurysmal, with a large patent foramen ovale (PFO) with continuous right to left shunting. Cardiac catheterization demonstrated oxygen saturations of 96% in the pulmonary veins and 74% in the left atrium with a significant right to left shunt. During percutaneous closure of the PFO, anaesthetic induction resulted in marked systemic hypotension and worsening hypoxia related to systemic vasodilatation and increased shunting. PFO flow was temporarily obstructed with a sizing balloon resulting in a rapid increase in arterial oxygen saturation from 60% to >90%, but marked systemic hypotension due to acute left ventricular preload reduction, requiring volume replacement and adrenaline. Following deployment of a PFO occluder device, prominent pulsatile splaying of the right and left discs was noted due to the severe tricuspid regurgitation, resulting in some residual inter-atrial shunting. Arterial oxygen saturation was 83%, increasing to 92% at day 4 post-procedure as tissue organization occurred within the device, and the patient reported improvement in dyspnoea.

Successful percutaneous closure of an extremely large secundum atrial septal defect during pregnancy.

Atrial septal defects (ASDs) are one of the most of the most common acyanotic congenital heart lesions. Awareness of potential clinical presentations and complications during pregnancy is essential for those managing these patients. We report successful percutaneous closure of an extremely large secundum ASD, using the largest available percutaneous ASD closure device in a 27-year-old pregnant female. Large ASDs may have their initial clinical presentation and diagnosis during pregnancy. If indicated, percutaneous closure can be performed safely. Only a very small number of cases have previously reported this being performed safely during pregnancy.

Documenting and harnessing the biological potential of molecules in Distributed Drug Discovery (D3) virtual catalogs.

Virtual molecular catalogs have limited utility if member compounds are (i) difficult to synthesize or (ii) unlikely to have biological activity. The Distributed Drug Discovery (D3) program addresses the synthesis challenge by providing scientists with a free virtual D3 catalog of 73,024 easy-to-synthesize N-acyl unnatural α-amino acids, their methyl esters, and primary amides. The remaining challenge is to document and exploit the bioactivity potential of these compounds. In the current work, a search process is described that retrospectively identifies all virtual D3 compounds classified as bioactive hits in PubChem-cataloged experimental assays. The results provide insight into the broad range of drug-target classes amenable to inhibition and/or agonism by D3-accessible molecules. To encourage computer-aided drug discovery centered on these compounds, a publicly available virtual database of D3 molecules prepared for use with popular computer docking programs is also presented.

Ethnic differences in coronary plaque and epicardial fat volume quantified using computed tomography.

Epidemiological studies observed a higher prevalence of coronary atherosclerosis in South Asians when compared to Caucasians, but quantitative computed tomography differences in aggregate plaque volume (APV) and epicardial fat volume (EFV) between South Asians, Southeast or East Asians (SEEAs) and Caucasians remain unknown. We aimed to compare APV and EFV quantified on computed-tomographic-coronary-angiography (CTCA) between South Asian, SEEA and Caucasian populations residing in Australia. Age, gender and body-mass-index matched subjects from three ethnic groups who underwent clinically indicated 320-detector CTCA were retrospectively analysed. Percentage APV in the first 5 cm of the left anterior descending artery (LAD) and EFV were quantified using dedicated software (Vital Images, USA). One-hundred-and-fifty subjects (average age = 57.7 years, 56 % male, n = 50 in each ethnic group) were analysed. Mean LAD percentage APV was highest in South Asians (44.5 ± 8.4 % vs. 37.5 ± 6.5 % in SEEAs and 39.5 ± 6.4 % in Caucasians, P = 0.00001). South Asian ethnicity predicted LAD APV above traditional risk factors on multivariate analysis (P = 0.000002). EFV was significantly higher in both South Asians (103.2 ± 41.7 cm3 vs. 85.8 ± 39.4 cm3, P = 0.035) and SEEAs (110.8 ± 36.9 cm3 vs. 85.8 ± 39.4 cm3, P = 0.001) when compared with Caucasians. In this cohort LAD percentage APV and EFV, as quantified on CTCA, differs between South Asians, SEEA and Caucasian populations, with higher LAD APV observed in South Asians and lower EFV in Caucasians. Atherosclerotic volume in LAD was best predicted by South Asian ethnicity above traditional risk factors and EFV. Further research is required to establish whether APV and EFV quantification can improve cardiac risk prediction in the South Asian population.

Cleaning and sterilization protocol for reused cardiac electrophysiology catheters inactivates hepatitis and coxsackie viruses.

OBJECTIVE: To assess the efficacy of a standard cleaning and sterilization protocol employed during reuse of cardiac electrophysiology catheters on the infectivity of duck hepatitis B virus (DHBV; a surrogate for human hepatitis B virus), bovine viral diarrhea virus (BVDV; a surrogate for human hepatitis C virus), and human coxsackie type B3 virus (CB3). SETTING: Public health virology laboratory. METHODS: Studies were performed on the distal, electrode-containing segments of 120 electrophysiology catheters previously used in up to 10 clinical procedures. Catheter segments were immersed for 1 hour in blood infected with high titers of DHBV, BVDV, or CB3. After air drying for 2 hours, subgroups of 8 catheters were subjected to no treatment, washing in general-purpose detergent, washing in enzyme cleaner, sterilization in ethylene oxide, or the full protocol of sequential detergent-enzyme cleaner-ethylene oxide exposure. Presence of residual virus was assessed by nucleic acid detection and infectivity studies. RESULTS: DHBV nucleic acid was detected on catheters after individual steps and the full protocol, whereas BVDV and CB3 nucleic acids were detected after individual steps but not the full protocol. These findings were associated with the presence of infectious DHBV and CB3, but not BVDV, on catheters after washing in detergent or enzyme cleaner. However, ethylene oxide alone or the full protocol reduced infectivity of all three viruses to undetectable levels. CONCLUSION: These experimental studies provide strong evidence that appropriate cleaning and sterilization of reused electrophysiology catheters inactivates blood-borne viruses such as hepatitis B and C and coxsackie type B3.

A decontamination and sterilization protocol employed during reuse of cardiac electrophysiology catheters inactivates human immunodeficiency virus.

OBJECTIVE: To assess the effect of a standard decontamination and sterilization protocol employed during reuse of cardiac electrophysiology (EP) catheters on human immunodeficiency virus (HIV). SETTING: Public health viral research laboratory. METHODS: Studies were performed on distal, electrode-containing segments of 40 EP catheters previously used in up to 10 clinical EP procedures. EP catheter segments were immersed for 1 hour in blood contaminated with a high titer of HIV. After air drying for 2 hours, subgroups of 8 EP catheters were subjected to either (1) no treatment, (2) washing in general purpose detergent, (3) washing in enzyme cleaner, (4) sterilization in ethylene oxide, or (5) the full protocol of sequential detergent-enzyme cleaner-ethylene oxide exposure. HIV infectivity after treatment was determined by measuring HIV RNA and, in cell culture studies, assessing HIV-induced cytopathic effects (CPEs) and supernatant HIV-specific p24 antigen content RESULTS: With no treatment, all catheters had high HIV RNA levels associated with CPEs and high p24 antigen levels. After washing in detergent, 5 of 8 catheters had HIV RNA detected, but without CPEs or p24 antigen. HIV RNA was detected in all catheters after washing in enzyme cleaner, with CPEs and a high p24 antigen level in 1 of 8 catheters. HIV RNA, CPEs, and p24 antigen were absent after ethylene oxide. After the full protocol, HIV RNA levels were undetectable (n = 7) or low (n = 1), without evidence of CPEs or p24 antigen. CONCLUSION: Appropriate decontamination and sterilization of EP catheters during reuse is highly effective in inactivating HIV.