Defining Patients at High Risk for Gastrointestinal Hemorrhage after Drug‐Eluting Stent Placement: A Cost Utility Analysis

Introduction: The study goal was to evaluate the cost‐effectiveness of drug‐eluting stent (DES) placement with consideration of gastrointestinal (GI) bleeding risk. DES reduce the need for future coronary revascularization, but require prolonged dual anti‐platelet (DAT) therapy, which may increase the risk for GI bleeding. While DES have been found to be cost‐effective in patients at average risk for GI bleeding, they may not be the most cost‐effective strategy in higher risk patients. Methods: A Markov model was created to compare DES with bare metal stents (BMS). Patients were a hypothetical cohort of 60‐year‐old individuals with coronary artery stenosis that required nonemergent percutaneous coronary revascularization (PCI). The primary outcomes were the threshold incremental risks of GI bleeding from DAT based on willingness to pay (WTP) of $50,000, $100,000, and $150,000 per quality adjusted life year (QALY) gained. Results: For a WTP of $100,000, the relative risk of GI bleeding from DAT could be as high as 10.8 (when compared to aspirin alone) before DES would no longer be cost‐effective. In patients with two risk factors for GI bleeding, the threshold relative risk could be as low as 1.6. Conclusion: In average‐risk patients, the risk of GI bleeding from DAT can be substantial without affecting the cost‐effectiveness of DES. However, DES are unlikely to be cost‐effective in patients with two or more risk factors for GI bleeding. (J Interven Cardiol 2010;23:179‐187)     

Fixed drug eruption: an immunohistochemical investigation of the acute and healing phase

Five patients were each challenged orally with a drug which had previously induced a fixed drug eruption. A positive reaction occurred in all the patients. Punch biopsies were taken 6-12 h, 24 h and 3 weeks after challenge. The specimens were tested with different mouse anti-human monoclonal antibodies to identify T lymphocytes and phenotypic subsets, natural killer cells, B lymphocytes, OKT-6 and HLA-DR-positive cells. T suppressor/cytotoxic cells seemed to play a major role in initiating the flare-up reaction and preserving the cutaneous memory function of the fixed drug eruption.     

The epidemiology of dermatomyositis in South Australia

Aim: To review the epidemiology of dermatomyositis (DM) in South Australia (SA) and to compare it with other Australian states and New Zealand (NZ). Methods: Muscle biopsy and hospital separation data for DM in SA, other Australian states, and NZ were determined. The role of environmental factors was investigated. Results: From 1990 to 2005, there were 21 cases of biopsy‐proven DM in SA (62% F, mean age 49.7 ± 18.4) and 99 cases of polymyositis (PM). Based on biopsy‐proven figures, the average incidence of DM per year in SA was 1.4 ± 1.2, and 6.6 ± 2.6 for PM. Since 1991, there were 221 and 441 total separations from SA hospitals with principal diagnoses of DM and PM, respectively. The ratio DM/DM + PM is thought to correlate with solar irradiance, and within Australia, SA had the lowest ratio (0.39, 95% CI 0.22–0.56), with the highest ratio seen in WA (0.67, 95% CI 0.53–0.81). This ratio did not correlate with latitude, duration of sunshine, cloud cover, relative humidity or total rainfall. Within SA, no correlation with socioeconomic status was seen. Australian data were similar to NZ, where the ratios were 0.34 and 0.3 for North and South Islands, respectively. As separation data reflect total hospital visits, we also ascertained individual patient separations from SA hospitals (1997 to July 2005) and found a similar ratio of DM/DM + PM (0.38 ± 0.08). Conclusions: The proportion of inflammatory myositis which is DM varies nationwide, with a consistent ratio seen in SA (33–38%). Geoclimatic variables do not appear to influence DM/PM disease expression in Australia.     

Implementation of monoclonal antibody fluorescence on the Abbott CELL‐DYN Sapphire haematology analyser: evaluation of lymphoid,myeloid and platelet markers

Apart from qualitative flags, that are typically inefficient and uninformative, haematology instruments provide little meaningful information about lymphocyte populations or the lineage of atypical or immature elements, The CELL‐DYN Sapphire haematology analyser uses integrated optical and fluorescence (488 nm) measurements, with FL1 (FITC) and FL2 (PE) detectors being configured for fluorescent analysis. As monoclonal antibodies (Mab) are widely used as cellular probes, and are likely to constitute the future basis for immunodifferentials, we explored the feasibility of implementing immunofluorescence on this routine haematology analyser. An extensive series of Mab (CD2, CD3, CD4, CD8, CD11b, CD13, CD14, CD16, CD19, CD22, CD33, CD34, CD41, CD42b, CD45, CD56, CD61, CD64, CD235a and HLA‐DR) were tested singly or in FITC/PE combinations. Analyser processing and data acquisition was achieved using CD‐Sapphire automated CD61 immunoplatelet or CD3/4/8 assay procedures and, apart from mixing EDTA‐blood and antibody, no further sample manipulation was required. Downloaded raw files were processed with cytometry software, and all evaluated reagents showed population discrimination analogous to flow cytometry. Practical procedures were straightforward and required minimal operator training. Extended information that can be obtained from monoclonal antibodies with a routine haematology analyser has the potential to extend haematology laboratory practices and positively impact laboratory and clinical efficiency.     

Risk Factors for Recurrent Heart Failure Events in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT‐II)

Risk Factors for Recurrent Heart Failure . Background: This study was designed to identify risk factors for recurrent heart failure (HF) events in patients with ischemic left ventricular dysfunction enrolled in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT‐II). Methods and Results: The Prentice, Williams, and Peterson (PWP) statistical model was utilized to identify and compare risk factors for 1 or ≥2 HF hospitalizations among 1,218 patients with ischemic left ventricular dysfunction enrolled in the MADIT‐II trial. Risk factors for a first HF hospitalization included treatment with an ICD (HR = 1.31; P = 0.05), New York Heart Association class >II (HR = 1.95; P < 0.001), female gender (HR = 1.38; P = 0.05), atrial fibrillation (HR = 1.90; P = 0.001), QRS >120 ms (HR = 1.41; P = 0.01), diabetes mellitus (HR = 1.51; P = 0.003), heart rate ≥80 (HR = 1.35; P = 0.04), diuretic therapy (HR = 1.82; P < 0.001), and the presence of prerenal azotemia (defined as blood urea nitrogen:creatinine >20; HR = 1.45; P = 0.01). In contrast, prerenal azotemia was the only risk factor that was independently associated with a significant increase in the risk of ≥2 HF hospitalizations (HR = 1.52; P = 0.027). The occurrence of 1 HF event after enrolment was associated with a 2.8‐fold (P < 0.001) increase in the risk of death, whereas after the occurrence of a second event there was a 6.7‐fold (P < 0.001) increase in the risk of subsequent mortality. Conclusions: In MADIT‐II, prerenal azotemia was the only significant and independent risk factor for HF progression after a first event, and recurrent HF was the most powerful predictor of mortality. These findings stress the importance of identifying risk factors for HF progression among patients who receive an ICD for primary prevention. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1217‐1223, November 2010)     

Autonomic Dysfunction and New‐Onset Atrial Fibrillation in Patients With Left Ventricular Systolic Dysfunction After Acute Myocardial Infarction: A CARISMA Substudy

Predicting New‐Onset AF. Background: Atrial fibrillation (AF) increases morbidity and mortality in patients with previous myocardial infarction and left ventricular systolic dysfunction. The purpose of this study was to identify patients with a high risk for new‐onset AF in this population using invasive and noninvasive electrophysiological tests. Methods: The study included 271 patients from the Cardiac Arrhythmias and RIsk Stratification after Myocardial InfArction (CARISMA) study with an acute myocardial infarction (AMI) and left ventricular ejection fraction ≤40% without previous AF at enrollment. Within 21 days after the AMI, an implantable loop recorder was inserted and used to diagnose AF over the 2‐year study duration. The following tests were performed: heart rate variability (HRV) and turbulence (HRT) analyses from repeated 24‐hour Holter recordings, 2‐dimensional (2D)‐echocardiograms, exercise test, and programmed electrophysiologic stimulation. Results: A total of 101 patients (37%) developed AF during the study. Predictive measures included several indexes of HRV including reduced low‐frequency (LF) power from spectral HRV analysis (adjusted HR = 1.6, P = 0.034), HRT slope ≤2.5 (HR = 1.6, P = 0.032) and Detrended Fluctuation Analysis (DFA1) from HRV analysis (HR = 1.8, P = 0.011); all are measures of cardiac autonomic nervous system dysfunction. Combined with age >60 years, low values for LF, HRT slope, and DFA1 provided a powerful risk score for prediction of new‐onset AF (1–2 points: HR = 4.3, P = 0.001, 3–4 points: HR = 7.0, P < 0.001). Conclusion: Abnormal HRV and HRT parameters, which are associated with disturbances in the cardiac autonomic regulation, are associated with increased risk of new‐onset AF independently of conventional clinical risk variables. (J Cardiovasc Electrophysiol, Vol. 21, pp. 983‐990, September 2010)     

Warfarin Is Not Needed in Low-Risk Patients Following Atrial Fibrillation Ablation Procedures

Background: The recently published HRS/EHRA/ECAS AF Ablation Consensus Statement recommended that warfarin should be used for at least 2 months following an AF ablation in all patients regardless of stroke risk factors. The objective of the study was to assess outcomes based upon anticoagulation practice after atrial fibrillation (AF) ablation to determine relative risk of a strategy of aspirin only in low-risk patients.
Methods: A total of 630 consecutive patients who underwent 934 ablation procedures using an open irrigated tip catheter for symptomatic AF were evaluated. Outcomes were compared between patients treated with warfarin (goal INR: 2–3) versus aspirin only (325 mg/day) in CHADS2 0–1 patients after ablation.
Results: Of the 690 patients, 123 (20%) were treated with aspirin and 507 (80%) with warfarin. Prevalences of the CHADS2 scores of patients on aspirin were (0: 40.7%, 1: 59.3%) and on warfarin (0: 13.6%, 1: 31.6%, ≥2: 54.8%), P < 0.0001. Patients in the warfarin group were older, had on average a lower ejection fraction, and had higher rates persistent/permanent AF, repeat ablations, hypertension, prior stroke/TIA, and diabetes. The 1-year survival free of AF for the total study population was 71.6%. There were no strokes/TIA in the aspirin group and 4 events (4 strokes, 0 TIAs) in the warfarin group. Two patients in the warfarin group died of fatal hemorrhage (1 intracranial, 1 gastrointestinal).
Conclusion: Select low-risk patients with a low CHADS2 (0–1) score who undergo left atrial ablation with an aggressive anticoagulation strategy with heparin and use of an open irrigated tip catheter with low CHADS2 scores can safely be discharged following their procedure on aspirin alone.     

IL-12 eliminates the Th-2 dependent protective immune response of mice to larval Strongyloides stercoralis

The goal of the present study was to determine if immune-mediated killing of S. stercoralis L3 in mice could be modulated by shifting from a Th-2 to a Th-1 type immune response. L3 killing in immunized mice was ablated in CD4⁺ T cell-depleted animals, but not in CD8⁺ T cell-depleted or β2-microglobulin-deficient mice. Treatment of immunized mice with IL-4 or IL-5 neutralizing MoAb significantly reduced the protective effects of vaccination against S. stercoralis , while protective immunity was unimpaired in IFN-γ knockout mice. Recombinant IL-12 was administered to infected mice to switch the immune response from a Th-2 to a Th-1 type response. Protective immunity was ablated in immunized mice that received IL-12 therapy. Eosinophil numbers, eosinophil peroxidase levels, and parasite-specific IgG1 levels were lowered in IL-12 treated immunized animals, and parasite-specific IgG2a levels were increased in these animals. The data indicate that eosinophils are important as mediators of larval killing, and that the establishment of Th-2 type immunity results in killing of infective S. stercoralis L3, while a shift to Th-1 type immunity abrogates protective responses.