Eosinophilic heart: Marked left ventricular wall thickening and myocardial dysfunction improving with corticosteroid therapy

We report a case of a 34-year-old male with acute severe heart failure associated with marked concentric left ventricular wall thickening and biopsy evidence of eosinophilic myocardial infiltrate. This appears to be an unusual description of this degree of concentric myocardial thickening in eosinophilic myocarditis coupled with Doppler tissue echocardiography. Following high-dose corticosteroid treatment, wall thickness, systolic and diastolic left ventricular function normalized and the patient experienced a dramatic clinical improvement. (ECHOCARDIOGRAPHY, Volume 20, May 2003).

Achieving better in-hospital and after-hospital care of patients with acute cardiac disease

In patients hospitalised with acute coronary syndromes (ACS) and congestive heart failure (CHF), evidence suggests opportunities for improving in-hospital and after hospital care, patient self-care, and hospital-community integration. A multidisciplinary quality improvement program was designed and instigated in Brisbane in October 2000 involving 250 clinicians at three teaching hospitals, 1080 general practitioners (GPs) from five Divisions of General Practice, 1594 patients with ACS and 904 patients with CHF. Quality improvement interventions were implemented over 17 months after a 6-month baseline period and included: clinical decision support (clinical practice guidelines, reminders, checklists, clinical pathways); educational interventions (seminars, academic detailing); regular performance feedback; patient self-management strategies; and hospital-community integration (discharge referral summaries; community pharmacist liaison; patient prompts to attend GPs). Using a before-after study design to assess program impact, significantly more program patients compared with historical controls received: ACS: Angiotensin-converting enzyme (ACE) inhibitors and lipid-lowering agents at discharge, aspirin and beta-blockers at 3 months after discharge, inpatient cardiac counselling, and referral to outpatient cardiac rehabilitation. CHF. Assessment for reversible precipitants, use of prophylaxis for deep-venous thrombosis, beta-blockers at discharge, ACE inhibitors at 6 months after discharge, imaging of left ventricular function, and optimal management of blood pressure levels. Risk-adjusted mortality rates at 6 and 12 months decreased, respectively, from 9.8% to 7.4% (P=0.06) and from 13.4% to 10.1% (P= 0.06) for patients with ACS and from 22.8% to 15.2% (P < 0.001) and from 32.8% to 22.4% (P= 0.005) for patients with CHF. Quality improvement programs that feature multifaceted interventions across the continuum of care can change clinical culture, optimise care and improve clinical outcomes.

A prospective multicentre study of pharmacist initiated changes to drug therapy and patient management in acute care government funded hospitals

Aims To determine the cost savings of pharmacist initiated changes to hospitalized patients' drug therapy or management in eight major acute care government funded teaching hospitals in Australia. Methods This was a prospective study performed in eight hospitals examining resource implications of pharmacists' interventions assessed by an independent clinical panel. Pharmacists providing clinical services to inpatients recorded details of interventions, defined as any action that directly resulted in a change to patient management or therapy. An independent clinical review panel, convened at each participating centre, confirmed or rejected the clinical pharmacist's assessment of the impact on length of stay (LOS), readmission probability, medical procedures and laboratory monitoring and quantified the resultant changes, which were then costed. Results A total of 1399 interventions were documented. Eight hundred and thirty-five interventions impacted on drug costs alone. Five hundred and eleven interventions were evaluated by the independent panels with three quarters of these confirmed as having an impact on one or more of: length of stay, readmission probability, medical procedures or laboratory monitoring. There were 96 interventions deemed by the independent panels to have reduced LOS and 156 reduced the potential for readmission. The calculated savings was $263 221 for the eight hospitals during the period of the study. This included $150 307 for length of stay reduction, $111 848 for readmission reduction. Conclusions The annualized cost savings relating to length of stay, readmission, drugs, medical procedures and laboratory monitoring as a result of clinical pharmacist initiated changes to hospitalized patient management or therapy was $4 444 794 for eight major acute care government funded teaching hospitals in Australia.

Activation of calcineurin in human failing heart ventricle by endothelin-1, angiotensin II and urotensin II

1 The calcineurin (CaN) enzyme-transcriptional pathway is critically involved in hypertrophy of heart muscle in some animal models. Currently there is no information concerning the regulation of CaN activation by endogenous agonists in human heart. 2 Human right ventricular trabeculae from explanted human ( 14 male/2 female) failing hearts were set up in a tissue bath and electrically paced at 1Hz and incubated with or without 100 nM endothelin-1 (ET-1), 10 mu M, angiotensin-II (Ang II) or 20 nM human urotensin-II (hUII) for 30 min. Tissues from four patients were incubated with 200 nM tacrolimus (FK506) for 30 min and then incubated in the presence or absence of ET-1 for a further 30 min. 3 ET-1 increased contractile force in all 13 patients (P < 0.001). Ang II and hUII increased contractile force in three out of eight and four out of 10 patients but overall nonsignificantly (P > 0.1). FK506 had no effect on contractile force (P = 0.12). 4 ET-1, Ang II and hUII increased calcineurin activity by 32, 71 and 15%, respectively, while FK506 reduced activity by 34%. ET-1 in the presence of FK506 did not restore calcineurin activity (P = 0.1). 5 There was no relationship between basal CaN activity and expression levels in the right ventricle. Increased levels of free phosphate were detected in ventricular homogenates that were incubated with PKC epsilon compared to samples incubated without PKCe. 6 Endogenous cardiostimulants which activate G alpha q-coupled receptors increase the activity of calcineurin in human heart following acute (30 min) exposure. PKC may contribute to this effect by increasing levels of phosphorylated calcineurin substrate.

Delayed administration of darbepoetin or erythropoietin protects against ischemic acute renal injury and failure

Administration of human recombinant erythropoietin ( EPO) at time of acute ischemic renal injury ( IRI) inhibits apoptosis, enhances tubular epithelial regeneration, and promotes renal functional recovery. The present study aimed to determine whether darbepoetin-alfa ( DPO) exhibits comparable renoprotection to that afforded by EPO, whether pro or antiapoptotic Bcl-2 proteins are involved, and whether delayed administration of EPO or DPO 6 h following IRI ameliorates renal dysfunction. The model of IRI involved bilateral renal artery occlusion for 45 min in rats ( N = 4 per group), followed by reperfusion for 1-7 days. Controls were sham-operated. Rats were treated at time of ischemia or sham operation ( T0), or post-treated ( 6 h after the onset of reperfusion, T6) with EPO ( 5000 IU/kg), DPO ( 25 mu g/kg), or appropriate vehicle by intraperitoneal injection. Renal function, structure, and immunohistochemistry for Bcl-2, Bcl-XL, and Bax were analyzed. DPO or EPO at T0 significantly abrogated renal dysfunction in IRI animals ( serum creatinine for IRI 0.17 +/- 0.05mmol/l vs DPO-IRI 0.08 +/- 0.03mmol/l vs EPO-IRI 0.04 +/- 0.01mmol/l, P = 0.01). Delayed administration of DPO or EPO ( T6) also significantly abrogated subsequent renal dysfunction ( serum creatinine for IRI 0.17 +/- 0.05mmol/l vs DPO-IRI 0.06 +/- 0.01mmol/l vs EPO-IRI 0.03 +/- 0.03mmol/l, P = 0.01). There was also significantly decreased tissue injury ( apoptosis, P < 0.05), decreased proapoptotic Bax, and increased regenerative capacity, especially in the outer stripe of the outer medulla, with DPO or EPO at T0 or T6. These results reaffirm the potential clinical application of DPO and EPO as novel renoprotective agents for patients at risk of ischemic acute renal failure or after having sustained an ischemic renal insult.

Erythropoietin protects against ischaemic acute renal injury

Erythropoietin (EPO) has recently been shown to exert important cytoprotective and anti-apoptotic effects in experimental brain injury and cisplatin-induced nephrotoxicity. The aim of the present study was to determine whether EPO administration is also renoprotectivein both in vitro and in vivo models ofischaemic acute renal failure Methods. Primary cultures of human proximal tubule cells (PTCs) were exposed to either vehicle or EPO (6.25–400 IU/ml) in the presence of hypoxia (1% O2), normoxia (21% O2) or hypoxia followed by normoxia for up to 24 h. The end-points evaluated included cell apoptosis (morphology and in situ end labelling [ISEL], viability [lactate dehydrogenase (LDH release)], cell proliferation [proliferating cell nuclear antigen (PCNA)] and DNA synthesis (thymidine incorporation). The effects of EPO pre-treatment (5000 U/kg) on renal morphology and function were also studied in rat models of unilateral and bilateral ischaemia–reperfusion (IR) injury. Results. In the in vitro model, hypoxia (1% O2) induced a significant degree of PTC apoptosis, which was substantially reduced by co-incubation with EPO at 24 h (vehicle 2.5±0.5% vs 25 IU/ml EPO 1.8±0.4% vs 200 IU/ml EPO 0.9±0.2%, n = 9, P

Are diagnosis specific outcome indicators based on administrative data useful in assessing quality of hospital care?

Background: Hospital performance reports based on administrative data should distinguish differences in quality of care between hospitals from case mix related variation and random error effects. A study was undertaken to determine which of 12 diagnosis-outcome indicators measured across all hospitals in one state had significant risk adjusted systematic ( or special cause) variation (SV) suggesting differences in quality of care. For those that did, we determined whether SV persists within hospital peer groups, whether indicator results correlate at the individual hospital level, and how many adverse outcomes would be avoided if all hospitals achieved indicator values equal to the best performing 20% of hospitals. Methods: All patients admitted during a 12 month period to 180 acute care hospitals in Queensland, Australia with heart failure (n = 5745), acute myocardial infarction ( AMI) ( n = 3427), or stroke ( n = 2955) were entered into the study. Outcomes comprised in-hospital deaths, long hospital stays, and 30 day readmissions. Regression models produced standardised, risk adjusted diagnosis specific outcome event ratios for each hospital. Systematic and random variation in ratio distributions for each indicator were then apportioned using hierarchical statistical models. Results: Only five of 12 (42%) diagnosis-outcome indicators showed significant SV across all hospitals ( long stays and same diagnosis readmissions for heart failure; in-hospital deaths and same diagnosis readmissions for AMI; and in-hospital deaths for stroke). Significant SV was only seen for two indicators within hospital peer groups ( same diagnosis readmissions for heart failure in tertiary hospitals and inhospital mortality for AMI in community hospitals). Only two pairs of indicators showed significant correlation. If all hospitals emulated the best performers, at least 20% of AMI and stroke deaths, heart failure long stays, and heart failure and AMI readmissions could be avoided. Conclusions: Diagnosis-outcome indicators based on administrative data require validation as markers of significant risk adjusted SV. Validated indicators allow quantification of realisable outcome benefits if all hospitals achieved best performer levels. The overall level of quality of care within single institutions cannot be inferred from the results of one or a few indicators.

Co-existing conditions for deaths from infectious and parasitic diseases in Australia

Objective: To examine the frequency distribution of co-existing conditions for deaths where the underlying cause was infectious and parasitic diseases. Materials and methods: Besides the underlying cause of death, the distributions of co-existing conditions for deaths from infectious and parasitic diseases were examined in total and by various age and sex groups, at individual and chapter levels, using 1998 Australian mortality data. Results: In addition to the underlying cause of death, the average number of reported co-existing conditions for a single infectious and parasitic death was 1.62. The most common co-existing conditions were respiratory failure, acute renal failure non-specific causes, ischaemic heart disease, pneumonia and diabetes. When studying the distribution of co-existing conditions at the ICD-9 chapter level, it was found that the circulatory system diseases were the most important. There was an increasing trend in the number of reported co-existing conditions from 60 years of age upwards. Gender differences existed in the frequency of some reported co-existing conditions. The most common organism types of co-existing conditions were other bacterial infection and other viruses. Conclusions: The study indicated that the quality of death certificates is less than satisfactory for the 1998 Australian mortality data. The findings may be helpful in clarifying the ICD coding rules and the development of disease prevention strategies. (C) 2003 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Effects of revascularisation and contractile reserve on left ventricular remodelling in patients with impaired left ventricular function

Objective: We sought to define the influence of revascularisation and contractile reserve on left ventricular (LV) remodelling in patients with LV dysfunction after myocardial infarction. Revascularisation of viable myocardium is associated with improved regional function, but the effect on remodelling is undefined. Methods: We studied 70 patients with coronary artery disease and LV dysfunction, 31 of whom underwent revascularisation. A standard dobutamine stress echocardiogram (DbE) was carried out. All patients underwent standard medical treatment; the decision to revascularise was made clinically, independent of this study. LV volumes and ejection fraction were measured by 3D echocardiography at baseline and after an average of 40 weeks. Results: There was no significant difference in baseline ejection fraction or volumes between patients who underwent revascularisation and the remainder. Compared to medically treated patients, revascularised patients had significant improvements in ejection fraction and end-systolic volume in follow-up. The impact of baseline variables on remodelling was assessed by dividing patients into tertiles of LV ejection fraction and volumes. Revascularised patients in the lowest tertile of ejection fraction at baseline (<38%) had a significant improvement in end-systolic volume and ejection fraction, larger than obtained in medically treated patients with low ejection fraction. Revascularised patients with an ejection fraction >38% did not show significant improvement in volumes compared to baseline. Revascularised patients in the largest tertiles of end-systolic (>88 ml) or end-diastolic volume (>149 ml) at baseline had a significant improvement in end-systolic volume. Conclusion: Remodeling appears to occur independent of the presence of regional contractile reserve but does correlate with the volume response to low-dose dobutamine. (C) 2003 Elsevier Ireland Ltd. All rights reserved.