Can we make sense of takotsubo cardiomyopathy? An update on pathogenesis, diagnosis and natural history.

Takotsubo cardiomyopathy (TTC) is a form of reversible acute cardiac dysfunction of uncertain pathogenesis, which occurs predominantly in postmenopausal women, often with antecedent severe stress. Systolic dysfunction most commonly affects the apex of the left ventricle. There is considerable uncertainty regarding the pathogenesis of TTC and the optimal diagnostic methodology. Acute catecholamine release may play a component role, but the regional hypokinesis is associated with an acute inflammatory process, with resultant early release of brain natriuretic peptide (BNP) and N-terminal pro-BNP. As the diagnosis of TTC has largely been a process of exclusion, there has been considerable underdiagnosis. The combination of demographics, preceding history, ECG appearances and N-terminal pro-BNP elevation may provide the basis for improved early diagnosis. Complete recovery takes at least several months, with a risk of recurrent episodes. Efforts to delineate pathogenesis, expedite diagnosis and evaluate residual disability may assist in the development of appropriate treatment regimens.

N-terminal pro-brain natriuretic protein levels in takotsubo cardiomyopathy.

Takotsubo cardiomyopathy (TTC) is characterized by reversible left ventricular (LV) systolic dysfunction independent of fixed coronary disease or coronary spastic pathogenesis. A number of investigators have documented marked elevation of natriuretic peptide levels at presentation in such patients. We sought to determine the pattern, extent, and determinants of the release of N-terminal pro-B type natriuretic peptide/B type natriuretic peptide (NT-proBNP/BNP) in patients with TTC. We evaluated NT-proBNP/BNP release acutely and during the first 3 months in 56 patients with TTC (96% women, mean age 69 ± 11 years). The peak plasma NT-proBNP levels were compared to the pulmonary capillary wedge pressure and measures of regional and global LV systolic dysfunction (systolic wall stress, wall motion score index, and LV ejection fraction) as potential determinants of NT-proBNP/BNP release. In patients with TTC, the plasma concentrations of NT-proBNP (median 4,382 pg/ml, interquartile range 2,440 to 9,019) and BNP (median 617 pg/ml, interquartile range 426 to 1,026) were substantially elevated and increased significantly during the first 24 hours after the onset of symptoms (p = 0.001), with slow and incomplete resolution during the 3 months thereafter. The peak NT-proBNP levels exhibited no significant correlation with either pulmonary capillary wedge pressure or systolic wall stress. However, the peak NT-proBNP level correlated significantly with the simultaneous plasma normetanephrine concentrations (r = 0.53, p = 0.001) and the extent of impairment of LV systolic function, as measured by the wall motion score index (r = 0.37, p = 0.008) and LV ejection fraction (r = -0.39, p = 0.008). In conclusion, TTC is associated with marked and persistent elevation of NT-proBNP/BNP levels, which correlated with both the extent of catecholamine increase and the severity of LV systolic dysfunction.

Secondary prevention for acute coronary syndrome in rural South Australia: are drugs best? What about the rest?

INTRODUCTION: Acute coronary syndrome (ACS) is a major cause of morbidity and mortality worldwide. Current Australian clinical guidelines recommend all patients with ACS receive comprehensive secondary prevention services to address this burden. Optimal patient outcomes rely on the timely and effective implementation of proven therapies and for secondary prevention to be successful, pharmacological interventions must be combined with cardiovascular disease (CVD) risk factor identification and management. The ability to implement clinical guidelines is also reliant on available resources, yet many rural populations in Australia do not have access to structured secondary prevention services, and the level of support available to them in the form of unstructured services is unclear. Our aim was to examine the scope of secondary prevention in a 'significantly restricted' rural region of South Australia that does not have access to structured secondary prevention services. METHODS: A retrospective analysis of medical records was undertaken to identify documented evidence of assessment and intervention for medical, lifestyle and behavioural CVD risk factors in hospital and at follow up in general practice (GP) clinics. Eligible participants were patients admitted to hospital in the Riverland Region of South Australia with myocardial infarction over a 12 month period. Of 77 eligible participants, permission was received to access the medical records of 55 patients in the hospital setting, and 34 of these 55 patients in GP clinic follow up. RESULTS: Most patients received baseline assessment for previous AMI (98%), history of hypertension (82%), history of diabetes (78%), and smoking status (76%). Most poorly documented was history of dyslipidaemia (53%) and obesity/ overweight (2%). Prescribing rates for recommended ACS medications at the time of hospital discharge were aspirin (90%), beta blockers (55%), ACE inhibitors (42%), lipid lowering medication (66%) and clopidogrel (64%). Overall prescribing rates in the 12 month study period rose to 80% or higher for all recommended medications. There was no evidence of interventions for smoking and obesity/ overweight in the hospital setting and 45% of smokers in the GP clinic setting received quit advice. Measurement of biomedical risk factors (blood lipid analysis and blood glucose levels) was suboptimal, and there was no evidence of a written action plan for chest pain for any participants. CONCLUSIONS: Unstructured services provided some of the recommended elements of secondary prevention. However, deficits in care exist that have the potential to negatively impact patient outcomes in this already disadvantaged population. Future research needs to focus on the extent to which this and other rural and remote health care services are working within current clinical guidelines for the management of ACS, and subsequent patient outcomes. Urgent consideration must also be given to the introduction and evaluation of a more structured and consistent approach in this and other rural and remote regions of Australia. The development of rehabilitation and prevention services that build on existing strengths and resources have the potential to widen access, enhance current services and ensure care is based on best practice guidelines. This in turn may reduce the burden of CVD and improve the overall health and quality of life for patients in rural and remote Australia.

The deleterious effects of hyperglycemia on platelet function in diabetic patients with acute coronary syndromes mediation by superoxide production, resolution with intensive insulin administration.

OBJECTIVES: This study sought to assess the determinants of platelet nitric oxide (NO) responsiveness in diabetic patients admitted with acute coronary syndromes (ACS) and the short-term effects of aggressive glycemic control on these factors. BACKGROUND: Hyperglycemia is an independent risk factor for mortality in both diabetic patients and nondiabetic patients with ACS. The mechanism(s) underlying this observation and potential benefit from its correction remain uncertain. Although a reduction in NO bioavailability has been proposed, this remains untested in the ACS setting. METHODS: A total of 76 diabetic patients with ACS were studied. Putative correlations between admission blood sugar level (BSL), inhibition of platelet aggregation by the NO donor sodium nitroprusside (SNP), and superoxide (O2-) were assessed. Hyperglycemic patients (n = 60) were randomized to acute glycemic control with intravenous versus subcutaneous insulin, and changes in the aforementioned parameters were compared. Plasma levels of the endogenous inhibitor of NO synthase asymmetric dimethylarginine (ADMA) were also monitored. RESULTS: There was an inverse correlation between admission BSL and both platelet SNP response (p = 0.007) and ADMA levels (p = 0.045), and a positive correlation with O2- generation (p < 0.001). Intravenous insulin infusion resulted in a greater reduction (p < 0.001) in BSL, differentially improved platelet responsiveness to SNP (p = 0.049), and decreased O2- (p < 0.001) and ADMA levels (p = 0.049). CONCLUSIONS: A component of platelet dysfunction in diabetic patients with ACS is impaired responsiveness to the anti-aggregatory effects of NO, probably reflecting increased NO clearance by O2-. This phenomenon is reversed by acute aggressive glycemic control. These findings provide a further rationale for use of insulin therapy in acute myocardial infarction and suggest its extension to ACS patients.