High rates of the SDHB p.Arg46Gln pathogenic variant predisposes New Zealand Maori to phaeochromocytoma/paraganglioma.

BACKGROUND: Phaeochromocytomas (PCC) and paragangliomas (PGL; together PPGL) are rare tumours of the adrenal medulla or extra-adrenal paraganglia. They may secrete catecholamines with significant cardiovascular effects. Management of PPGL is predominantly surgical, despite the anaesthetic risks related to potential haemodynamic instability. Meticulous pre-treatment and intra-operative management are required to improve cardiovascular outcomes. AIMS: There are limited local data regarding the incidence of PPGL and the clinical characteristics of individuals diagnosed with these tumours in New Zealand. We undertook a retrospective study investigating the local practice and patient characteristics with an additional focus on intra-operative haemodynamic stability and post-operative outcomes. METHODS: Electronic patient records were searched for individuals with a diagnosis of PPGL. Clinical records and electronic databases were interrogated for pre-operative, intra-operative and post-operative data points. Particular attention was paid to rates and types of germline mutations, intra-operative haemodynamic stability and post-operative renal and cardiovascular outcomes. RESULTS: We identified 49 individuals with PPGL, of whom 34 were from the local area. This gave a local incidence of PPGL of around five cases per million people per year. Maori were significantly over-represented in our cohort, with this being in part due to high rates of the SDHB R46Q mutation. Over 95% of our cohort met pre-specified pre-operative blood pressure parameters. Intra-operative monitoring revealed a tendency to hypotension, but this did not translate into adverse post-operative outcomes, which were infrequent. CONCLUSIONS: Maori were over-represented due to high rates of germline SDHB R46Q mutations. There were few post-operative adverse outcomes in this contemporary cohort.

Mortality after discharge from hospital following an episode of diabetic ketoacidosis.

AIMS: The rate of inpatient mortality associated with diabetic ketoacidosis (DKA) has steadily decreased in recent decades. However, there remains a significantly increased outpatient death rate following an episode of survived DKA. We undertook this study to investigate the observed increase in mortality following an episode of DKA. METHODS: We completed a retrospective cohort study to investigate rates and causes of death in people admitted to our hospital with DKA between 2013 and 2018. DKA was confirmed by pre-defined biochemical parameters and cause of death data was extracted from multiple sources. Follow-up was for two years after discharge for all participants with one-year mortality being the main time point for analysis. RESULTS: We identified 818 admissions to hospital with DKA, affecting 284 people. Twenty people died as inpatients and a further 40 people died during the two-year follow-up. Of these 60 participants, cause of death was able to be determined for 41 (68%), with most deaths occurring due to infection or macrovascular disease. Risk factors for death within a year of hospital discharge included older age, vascular complications of diabetes, intellectual impairment and residential care living. Those who survived an episode of DKA had a one-year age-corrected mortality rate 13 times higher than the general population. This was more marked in the younger cohort with those aged 15-39 years being 49 times more likely to die in the year after surviving a DKA admission compared to their general population counterparts. CONCLUSION: An episode of diabetic ketoacidosis is associated with a significant outpatient mortality risk with most deaths due to infectious or macrovascular causes. This study should prompt investigation of predictive scoring tools to identify those at increased mortality risk after DKA and encourage the development of targeted interventions to reduce mortality.

Increased Peripheral Blood Heteroplasmy of the mt.3243A>G Mutation Is Associated with Earlier End-Stage Kidney Disease: A Case Report and Review of the Literature.

The mitochondrial DNA mutation mt.3243A>G is most commonly associated with maternally inherited diabetes and deafness (MIM 52,000), but it has protean phenotypes including renal disease due to focal segmental glomerulosclerosis. We describe monozygotic twins who both harboured this mutation and developed ESRD. Although otherwise genetically identical, the twins differed in their peripheral blood leucocyte levels of circulating mt.3243A>G heteroplasmy: 20 versus 10%, when assessed at 42 years of age. The twin with the higher heteroplasmy load developed end-stage kidney disease 15 years earlier than her sister. A review of the published literature supports a relationship between heteroplasmy level and the age at the development of the end stage of renal failure in patients with mt.3243A>G-related kidney disease.

The Fentanyl Patch Boil-Up - A Novel Method of Opioid Abuse.

Fentanyl is a potent opioid analgesic used in the treatment of pain. Transdermal fentanyl patches are now widely utilized as an acceptable and efficacious method of medication delivery. Unfortunately, the potential for their abuse is well recognized. Previous case reports have documented deaths after intravenous (IV) misuse of fentanyl which had been extracted from Duragesic (liquid reservoir type) patches. We present a case of IV fentanyl abuse after the extraction from a Mylan (matrix type) patch. This method of abuse has not previously been described in the literature.

A prospective intravascular ultrasound investigation of the necessity for and efficacy of postdilation beyond nominal diameter of 3 current generation DES platforms for the percutaneous treatment of the left main coronary artery.

OBJECTIVES: To define the size of the left mainstem coronary artery (LMS) in the Northern Irish population and investigate the clinical feasibility, safety, and efficacy of post dilation beyond nominal diameter of current generation Drug eluting stent (DES) when treating the LMS. BACKGROUND: There is no prospective data examining the need, feasibility, and safety of over-expansion of current generation DES beyond nominal diameter. METHODS: Patients with flow-limiting coronary atheroma requiring IVUS assessment of the LMS were recruited. Standardized measurements of the distal LMS were made. Subsequently, patients requiring post dilation of current generation DES within the LMS were entered into a PCI registry. RESULTS: Overall, 125 patients were recruited into the initial study. Mean cross-sectional area (CSA) of the distal LMS was 22.6 mm(2) (SD ± 5.4 mm(2) ). Mean maximal vessel diameter was 5.7 mm (SD ± 0.7 mm). Increasing plaque burden was associated with reduced CSA (P < 0.001). In 31 consecutive patients undergoing IVUS guided PCI of the LMS with 5.5 and 6.0 mm balloon catheters, mean maximal stent diameters were >5.0 mm with the Biomatrix Flex 9 crown and Promus Element Large vessel platforms. No intraprocedural complications occurred. Mean follow up was 13.4 months. Clinical restenosis rate was 3.2%, with 2 deaths unrelated to index procedure. CONCLUSIONS: The majority of patients with angiographic coronary atheroma have a mean LMS diameter of >4 mm indicating the requirement for post dilation beyond nominal diameter all of current generation DES in almost all patients when treating the LMS. This is achievable with current DES platforms with no intraprocedural complication. Clinical follow up indicates excellent short-term efficacy.

An audit of outcomes after same-day discharge post-PCI in acute coronary syndrome and elective patients.

OBJECTIVES: To investigate the outcomes of a cohort of acute and elective percutaneous coronary intervention (PCI) patients who were discharged home 6 hours postprocedure. BACKGROUND: Contemporary PCI is safe with a low rate of acute complications. It is well established as a day procedure in elective cases; however, data are lacking in acute cases. METHODS: We describe a prospective observational audit of routine clinical practice in the 3 PCI centers in Northern Ireland. Patients were selected for same-day discharge after 6 hours of post-PCI observation. Both elective and acute coronary syndrome (ACS) cases were included. Criteria for same-day discharge were based on the technical result of the procedure rather than lesion complexity or clinical presentation. Radial access was preferred but not mandatory. Patients were contacted directly to assess for 30-day major adverse cardiovascular events (MACE). Reported events were corroborated with the general practitioner or hospital notes. RESULTS: A total of 1,059 patients were selected for same-day discharge with 30-day follow-up available for all cases. Of these, 766 (72.3%) were elective and 293 (27.7%) were ACS patients. Radial access was almost universal (98%). A total of 1,224 lesions were stented, of which 432 (40.8%) were high risk (highest risk lesion in each case by AHA/ACC classification). MACE rate at 30 days was 0.85% with a sub-acute stent thrombosis rate of 0.4%. There were no MACE events from discharge to 24 hours. CONCLUSIONS: Selected acute and elective patients with a range of lesion complexity and risk can be discharged safely home early after PCI.

Advances in cardiology: clinical trial update.

Multiple key cardiology trials have been presented or published over recent months, several with the potential to change clinical practice. In this article, we summarize and place in clinical context new trial findings regarding anticoagulation in the cardiac catheterization laboratory (enoxaparin, fondaparinux and unfractionated heparin), the implications of genetic polymorphisms and functional testing for antiplatelet therapy (clopidogrel and ticagrelor), new oral anticoagulants for use in atrial fibrillation (apixiban and rivaroxaban), optimal pacing strategies and pharmacological agents in heart failure (ivabradine, eplerenone, cardiac resynchronization therapy, telemonitoring and intracoronary bone marrow stem cell infusion). Clinical trials in percutaneous structural intervention (transcatheter aortic valve implantation, MONARC™ mitral annular implant, STARFlex(®) patent foramen ovale device) and advanced percutaneous coronary intervention (everolimus-eluting stents, biodegradable polymer/polymer-free technologies and contemporary use of intravascular ultrasound) are also discussed.

Ticagrelor: from concept to clinical evaluation.

Dual antiplatelet therapy with aspirin and a platelet adenosine diphosphate P2Y(12) receptor blocker reduces the risk of major adverse cardiovascular events following percutaneous coronary intervention or an acute coronary syndrome. Clopidogrel is the most widely used P2Y(12) receptor blocker, but has suboptimal speed of onset of action and maximal platelet inhibition, as well as variability in the inhibition of platelet aggregation achieved. Therefore, novel P2Y(12) receptor blockers have been developed to address these limitations, including prasugrel and ticagrelor. This article describes the pharmacokinetic and pharmacodynamic evaluation of ticagrelor, which has been demonstrated to have significantly faster onset, faster offset, greater maximal inhibition of platelet aggregation and less variability in response compared with clopidogrel. These detailed Phase II data helped guide the design of the large landmark clinical trial Platelet Inhibition and Patient Outcomes (PLATO; n = 18,624 patients with acute coronary syndrome) in which ticagrelor was associated with a 16% relative risk reduction in the primary composite end point of cardiovascular death, myocardial infarction or stroke at 12 months (9.8 vs 11.7%; hazard ratio: 0.84; 95% CI: 0.77-0.92; p < 0.001). Ongoing trials are evaluating the clinical value of individualizing therapy according to on-treatment residual platelet activity, genetic polymorphism (loss-of-function allele status) and by improved safety/efficacy risk stratification.

Recent advances in cardiology.

During 2009, multiple major cardiology trials have been presented or published. In this paper, we summarize and place in clinical context the new trial findings regarding anticoagulation (dabigatran), antiplatelet therapy (ticagrelor, clopidogrel, prasugrel and aspirin), percutaneous coronary management (thrombectomy, multivessel/left main disease and biodegradable polymers), medical therapy for coronary disease (ivabradine and rosuvastatin) and management of heart failure (beta-blocker strategy, atrial fibrillation and resynchronization therapy).