East Indian Sandalwood Oil Is a Phosphodiesterase Inhibitor: A New Therapeutic Option in the Treatment of Inflammatory Skin Disease.

Cyclic adenosine monophosphate phosphodiesterases (PDEs) regulate pro-inflammatory cytokine production. One isoform, PDE4, is overactive in chronic relapsing inflammatory skin diseases: psoriasis and eczema/atopic dermatitis, and in several cancers. East Indian sandalwood oil (EISO) has significant anti-inflammatory properties. Here, we report that 75% of pediatric eczema/atopic dermatitis patients treated with topical EISO formulations achieved a >50% reduction in their Eczema Area and Severity Index score. EISO treatment of a psoriasis model reduced PDE4 expression and reversed histopathology. EISO directly inhibited PDE enzymatic activity in vitro. In lipopolysaccharide-stimulated human dermal fibroblast, BEAS-2B, A549, and THP-1 cells, EISO suppressed total cellular PDE activity, PDE4, and 7 transcript levels, nuclear factor kappa B (NF-κB) activation, and pro-inflammatory cytokines/chemokine production. These results suggest that EISO anti-inflammatory activity is mediated through suppressing PDE activity, thus facilitating cAMP-regulated inhibition of NF-κB and indicate EISO as an attractive natural therapeutic for chronic and acute inflammatory disorders.

East Indian Sandalwood Oil (EISO) Alleviates Inflammatory and Proliferative Pathologies of Psoriasis.

Psoriasis, a chronic inflammatory skin disease marked by hyper proliferation and aberrant differentiation of keratinocytes, affects 2-3% of the world's population. Research into the pathogenesis of psoriasis has been hampered by the lack of models that accurately reflect the biology of the psoriatic phenotype. We have previously reported that East Indian Sandalwood oil (EISO) has significant anti-inflammatory properties in skin models and hypothesized that EISO might provide therapeutic benefit to psoriasis patients due to its anti-inflammatory and anti-proliferative properties. Here we present interim results from an on-going proof-of-concept Phase 2 clinical trial in which topically applied EISO is demonstrating to be well tolerated and helpful in alleviating mild to moderate psoriasis symptoms. This led us to evaluate the ability of EISO to affect the psoriatic phenotype using MatTek Corporation reconstituted organotypic psoriatic and normal human skin models. EISO had no impact on the phenotype of the normal skin tissue model, however, EISO treatment of the psoriasis tissue model reverted psoriatic pathology as demonstrated by histologic characterization and expression of keratinocyte proliferation markers, Ki67 and psoriasin. These phenotypic affects correlated with suppressed production of ENA-78, IL-6, IL-8, MCP-1, GM-CSF, and IL-1ß. Demonstration of the ability of EISO to abrogate these psoriasis symptoms in well-characterized in vitro psoriatic tissue models, supports the hypothesis that the clinically observed symptom alleviation is due to suppression of intrinsic tissue inflammation reactions in afflicted lesions. This study presents a systematic approach to further study the underlying mechanisms that cause psoriasis, and presents data supporting the potential of EISO as a new ethnobotanical therapeutic concept to help direct and accelerate the development of more effective therapies.

Development and feasibility testing of an oral hygiene intervention for stroke unit care.

OBJECTIVE: To develop an oral hygiene complex intervention and evaluate its feasibility in a single UK stroke centre. BACKGROUND: Oral hygiene interventions might improve clinical outcomes after stroke but evidence-based practice is lacking. MATERIALS AND METHODS: We used a sequential mixed methods approach and developed an oral hygiene complex intervention comprising: (i) web-based education and 'hands-on' practical training for stroke unit nursing staff, (ii) a pragmatic oral hygiene protocol consisting of twice-daily powered (or manual if preferred) brushing with chlorhexidine gel (or non-foaming toothpaste) ± denture care. We evaluated feasibility of (i) the staff education and training and (ii) the oral hygiene protocol in consenting inpatients with confirmed stroke, requiring assistance with at least one aspect of personal care. RESULTS: The staff education and training were feasible, acceptable and raised knowledge and awareness. Several barriers to completing the education and training were identified. The oral hygiene protocol was feasible and well-tolerated. 22% of eligible patients screened declined participation in the study. Twenty-nine patients (median age = 78 year; National Institutes of Health Stroke Scale score = 8.5; 73% dentate) were recruited at a median of 7 days from stroke onset. 97% of participants chose the default chlorhexidine-based protocol; the remainder chose the non-foaming toothpaste-based protocol. The mouth hygiene protocol was administered as prescribed on 95% of occasions, over a median duration of 28 days. There were no adverse events attributed to the oral hygiene protocol. CONCLUSION: Our oral hygiene complex intervention was feasible in a single UK stroke centre. Further studies to optimise patient selection, model health economics and explore efficacy are now required.

Prognostic significance of (123)I-mIBG SPECT myocardial imaging in heart failure: differences between patients with ischaemic and non-ischaemic heart failure.

AIMS: The purpose of this study was to examine the prognostic significance of uptake patterns on quantitative myocardial (123)I-mIBG and (99m)Tc-tetrofosmin SPECT imaging in heart failure (HF) subjects and to assess the differences between patients with ischaemic and non-ischaemic HF. METHODS AND RESULTS: Results of quantitative analyses of (123)I-mIBG myocardial SPECT, alone and in combination with (99m)Tc tetrofosmin SPECT, were studied in 619 ischaemic (I) and 319 non-ischaemic (NI) HF subjects from the ADMIRE-HF trial. Cardiac and all-cause mortality data for 2-year follow-up were collected in the extension study (ADMIRE-HFX) and were examined in relation to extent and severity of voxel-based defects, the number of myocardial segments with significant dysinnervation (derived score ≥2), and (123)I-mIBG/(99m)Tc tetrofosmin mismatch quantitation. Cox proportional hazards and survival analyses were used to identify higher and lower risk groups and to define thresholds for optimal discrimination between the two. Two-year all-cause and cardiac mortality were not significantly different between IHF and NIHF subjects. Mortality was higher in patients with dysinnervation involving >50% of the myocardium. Highest cardiac mortality risk for IHF subjects was seen with perfusion defects involving 20-40% of the myocardium. By comparison, NIHF subjects with smaller perfusion abnormalities (<20% of myocardium), but with a large discrepancy between (123)I-mIBG and (99m)Tc tetrofosmin defect sizes, were at highest risk of cardiac death. CONCLUSIONS: Prognostic significance of patterns of (123)I-mIBG and MPI uptake differ between IHF and NIHF subjects. SPECT imaging may provide new insights into underlying disease processes in HF, including the degree of dysinnervation in areas with preserved myocardial perfusion in non-ischaemic HF patients.

Quantitative iodine-123-metaiodobenzylguanidine (MIBG) SPECT imaging in heart failure with left ventricular systolic dysfunction: Development and validation of automated procedures in conjunction with technetium-99m tetrofosmin myocardial perfusion SPECT.

BACKGROUND: The purpose of this study was to develop and validate new approaches to quantitative MIBG myocardial SPECT imaging in heart failure (HF) subjects. METHODS AND RESULTS: Quantitative MIBG myocardial SPECT analysis methods, alone and in conjunction with 99mTc-tetrofosmin perfusion SPECT, were adapted from previously validated techniques for the analysis of SPECT and PET perfusion imaging. To account for underestimation of MIBG defect severity in subjects with global reduction in uptake, a mixed reference database based on planar heart/mediastinum (H/M) ratio categories was used. Extent and severity of voxel-based defects and number of myocardial segments with significant dysinnervation (derived score ≥2) were determined. MIBG/99mTc-tetrofosmin mismatch was quantified using regions with preserved innervation as the reference for scaling 99mTc-tetrofosmin voxel maps. Quantification techniques were tested on studies of 619 ischemic (I) and 319 non-ischemic (NI) HF subjects. Using all analytical techniques, IHF subjects had significantly greater and more severe MIBG SPECT abnormalities compared with NIHF subjects. Innervation/perfusion mismatches were also larger in IHF subjects. Findings were consistent between voxel- and myocardial-segment-based quantitation methods. CONCLUSIONS: Multiple objective methods for quantitation of MIBG SPECT imaging studies provided internally consistent results for distinguishing the different patterns of uptake between IHF and NIHF subjects.

Outcome prediction in heart failure with atrial fibrillation: relative role of left ventricular ejection fraction and neurohormonal measures.

BACKGROUND: Since atrial fibrillation (AF) impacts the measurement and interpretation of left ventricular ejection fraction (LVEF), we hypothesized that the outcome in heart failure (HF) with AF and LVEF ≤ 35% would be more strongly associated with neurohormonal measures than LVEF. METHODS AND RESULTS: Cardiac adverse events [CAE; HF progression (HFP), life-threatening arrhythmia (ARR), and cardiac death (CD)] and all-cause mortality (ACM) were recorded prospectively in 954 patients with HF and LVEF ≤ 35%: 852 in sinus rhythm (SR) and 102 in AF. Cox proportional hazard models found that the univariate hazard ratios (HR) for LVEF and the first CAE (primary outcome), HFP, ARR, CD, and ACM were significant in SR (0.933, P < .001, 0.933, P < .001, 0.929, P < .001, 0.916, P < .001, 0.945, P = .001, respectively), but not in AF (1.002, P = .95, 1.060, P = .24, 0.922, P = .15, 0.885, P = .09, 0.932, P = .25). HRs for CAEs and ACM and one or more neurohormonal measures (iodine 123 m-iodobenzylguanidine cardiac parameters, B-type natriuretic peptide, and plasma norepinephrine) were significant in SR and AF. The multivariate models for the first CAE and HFP included neurohormonal measures and LVEF in SR and neurohormonal measures in AF. CONCLUSIONS: In HF with LVEF ≤ 35% with AF, neurohormonal measures, but not LVEF, were related to outcomes.

Measurement of left and right ventricular volumes with tomographic equilibrium radionuclide angiocardiography and cardiac MRI.

OBJECTIVE: We previously developed an operator-interactive method for the measurement of left ventricular (LV) and right ventricular (RV) ejection fraction (EF) and end-systolic volume (ESV) and end-diastolic volume (EDV) using single-photon emission tomographic equilibrium radionuclide angiocardiography (SPECT ERNA). We aimed to compare our SPECT ERNA method with cardiac MRI (CMRI) for the determination of ventricular measures. METHODS: Paired measurements of LV and RV EFs and ESV and EDV were carried out by SPECT ERNA and CMRI in a group of patients who had myocardial infarction due to left anterior descending coronary artery thrombosis. RESULTS: SPECT ERNA and CMRI provided similar estimations of the mean (SD) LV ESV [61 (23) vs. 61 (32) ml; P=0.99] and LV EDV [134 (29) vs. 141 (44) ml; P=0.28]. The mean (SD) LV EF by SPECT ERNA was slightly but significantly smaller than that by CMRI [0.55 (0.10) vs. 0.58 (0.11) ml; P=0.03]. SPECT ERNA, compared with CMRI, produced similar mean (SD) values of RV ESV [62 (17) vs. 67 (17) ml; P=0.10] and RV EDV [153 (28) vs. 149 (29) ml; P=0.51] and somewhat larger mean (SD) RV EF [0.60 (0.06) vs. 0.55 (0.06) ml; P<0.001]. Excellent correlations were found between SPECT ERNA and CMRI for combined LV ESV and EDV (R=0.85, P<0.001) and combined RV ESV and EDV (R=0.85, P<0.001). CONCLUSION: This study further validates SPECT ERNA as a method to measure LV and RV EF, ESV, and EDV.

Influence of diabetes mellitus on prognostic utility of imaging of myocardial sympathetic innervation in heart failure patients.

BACKGROUND: Patients with diabetes mellitus have accelerated progression of heart failure and often have impaired cardiac sympathetic innervation. The present study examines the implications for heart failure progression of cardiac sympathetic denervation, assessed by I-123 metaiodobenzylguanidine imaging, in diabetic compared with nondiabetic subjects. METHODS AND RESULTS: We evaluated 343 diabetic and 618 nondiabetic subjects with New York Heart Association class II or III heart failure and a left ventricular ejection fraction ≤35% over a median follow-up of 17 months. A multivariable Cox proportional hazards model was used to examine the influence of clinical variables, b-type natriuretic peptide, plasma norepinephrine, left ventricular ejection fraction, and I-123 metaiodobenzylguanidine imaging parameters on time to a heart failure event. The late heart-to-mediastinum (H/M) ratio and the interaction term of diabetes mellitus with the prospectively selected late H/M ratio <1.6 were independent predictors of heart failure progression, providing incremental prognostic information beyond that available from all other variables. In diabetic subjects, late H/M ratio <1.6 was associated with a 2.99-fold greater 2-year rate of heart failure progression (33.5%) than late H/M ratio ≥1.6 (11.2% event rate). CONCLUSIONS: The combination of diabetes mellitus and I-123 metaiodobenzylguanidine H/M ratio is an independent predictor of heart failure progression, confirming the high risk of diabetic subjects with impaired cardiac sympathetic nerve function.

Symptom improvement after upgrade from right ventricular apical to biventricular pacing: Role of right and left ventricular volumes assessed with single-photon emission computed tomographic equilibrium radionuclide angiocardiography.

BACKGROUND: In patients with heart failure and reduced left ventricular ejection fraction (LVEF), the effect of upgrading from right ventricular (RV) apical to biventricular pacing on RV and left ventricular (LV) volumes and ejection fraction (EF) is unknown. Also, the relationship of symptom improvement after biventricular upgrade to RV and LV volumes and EF has not been clarified. METHODS AND RESULTS: Nineteen patients with long-standing persistent RV apical pacing who had heart failure symptoms and echocardiographic LVEF of 0.40 or less underwent upgrade to biventricular pacing. Patients had single-photon emission computed tomographic equilibrium radionuclide angiocardiography immediately before and at 3-6 months after the upgrade procedure, to measure RV and LV volumes and EF. Biventricular upgrade was associated with increase in LVEF and decrease in LV end-diastolic and end-systolic volumes; right ventricular ejection fraction (RVEF) and end-diastolic and end-systolic volumes were unaltered. Patients with improvement in New York Heart Association heart failure class of I or more had larger initial LV end-diastolic volumes than patients without an improvement and had decreased LV end-diastolic and end-systolic volumes comparatively. Symptom improvement was not associated with RVEF and volume change. CONCLUSION: Symptom improvement with LV remodeling, but not RV remodeling, occurs 3-6 months after biventricular upgrade in patients with heart failure.

Reliability of confocal microscopy spectral imaging systems: use of multispectral beads.

BACKGROUND: There is a need for a standardized, impartial calibration, and validation protocol on confocal spectral imaging (CSI) microscope systems. To achieve this goal, it is necessary to have testing tools to provide a reproducible way to evaluate instrument performance. METHODS: We evaluated fluorescent spectral beads (FocalCheck) from Molecular Probes/Invitrogen that consist of four pairs with emissions between 500 and 725 nm and a europium macrocycle quantum dye bead. These bead tools compliment our previously published protocol for testing spectral imaging systems that used an inexpensive multi-ion discharge lamp (MIDL) that contains Hg(+), Ar(+), and inorganic fluorophores that emits distinct, stable spectral features. RESULTS: We acquired the spectra of the FocalCheck beads on a Zeiss 510 Meta, a Leica TCS-SP1, a Leica SP2 AOBS, an Olympus FV 1000, and a Nikon C1Si confocal systems and a PARISS microscopic spectral system and of the europium beads on the Leica TCS-SP1 and PARISS spectral imaging systems. A lack of performance with some equipment between 650 and 750 nm was identified using the far red pair of the FocalCheck beads. The position of the slider in front of PMT 2 that reflects light into PMT 1 and PMT 3 affected the measurement of all bead intensities. Unmixing algorithms were used to separate beads with different fluorochromes and separate two fluorochromes on the same bead. CONCLUSIONS: The FocalCheck multi-spectral beads yielded similar profiles on four CSI systems and a PARISS spectral system. The utilization of the spectral FocalCheck beads is helpful to evaluate proper spectral performance, especially in the far red region. Europium beads provide a very narrow spectrum that can help to identify machines that have spectral problems. The dyes located on individual beads or mixed together in ring-core configuration can be used as test particles to demonstrate spectral unmixing with various algorithms.

Assessment of pulmonary thromboendarterectomy by tomographic electrocardiogram-gated equilibrium radionuclide angiocardiography compared with electron beam computed tomography.

BACKGROUND: Successful thromboendarterectomy for chronic thromboembolic pulmonary hypertension promptly improves right ventricular (RV) function by decreasing RV volume and increasing ejection fraction (EF). Single photon emission computed tomography (SPECT) equilibrium radionuclide angiocardiography (ERNA) has been validated as a measure of RV and left ventricular (LV) volume and EF. METHODS AND RESULTS: Nine patients with chronic thromboembolic pulmonary hypertension underwent electron beam computed tomography (EBCT) and SPECT ERNA cardiac studies before and after thromboendarterectomy. EBCT and SPECT ERNA measures of RV and LV volume and EF were compared. Before thromboendarterectomy, EBCT and SPECT ERNA RV and LV volumes and RV EF were similar. LV EF was within the normal range with both methods but was slightly greater (P = .004) when measured by EBCT (mean +/- SD, 0.61 +/- 0.08) compared with SPECT ERNA (0.54 +/- 0.10). Thromboendarterectomy measured by EBCT and SPECT ERNA produced marked similar and significant decreases in RV end-systolic (-72 +/- 59 mL vs -58 +/- 25 mL) and end-diastolic (-75 +/- 85 mL vs -76 +/- 32 mL) volumes and similar slight increases in RV EF (0.12 +/- 0.07 vs 0.05 +/- 0.06). Slight decreases in mean LV end-systolic (-19 +/- 23 mL vs -5 +/- 13 mL, P = .05) and end-diastolic (-32 +/- 53 mL vs -9 +/- 31 mL, P = .21) volumes occurred, with little change in mean LV EF (0.05 +/- 0.07 vs 0.00 +/- 0.10). CONCLUSIONS: SPECT ERNA is an accurate method for measuring RV and LV volume and EF before and after thromboendarterectomy.

Frequency and determinants of early rapid filling abnormality.

BACKGROUND: The frequency and determinants of early rapid diastolic filling abnormalities in the community and in cardiac patients are poorly understood. METHODS AND RESULTS: Early left ventricular (LV) rapid filling was assessed via equilibrium radionuclide angiocardiography in 70 community volunteers (LV ejection fraction [EF] > or = 0.50) and 778 cardiac patients, all aged at least 45 years. The frequency of early rapid filling and the independent clinical, therapeutic, and hemodynamic variables predictive of early rapid filling abnormality were determined. Depending on the parameter assessed, early rapid filling was abnormal in 27% to 54% of the community volunteers, 34% to 53% of cardiac patients with an LVEF of 0.50 or greater, and 42% to 67% of cardiac patients with an LVEF lower than 0.50. On the basis of multivariate analysis, models of clinical, therapeutic, and hemodynamic variables were modestly predictive of early rapid filling abnormality. Age, sex, valvular insufficiency, hypertension, digoxin use, and heart rate were independent determinants of early rapid filling. CONCLUSIONS: In participants aged older than 44 years, early rapid filling was frequently abnormal in the community volunteers and in patients with an LVEF of 0.50 or greater and was most common in patients with an LVEF lower than 0.50. Clinical, therapeutic, and hemodynamic variables had modest independent predictive value for early rapid filling abnormality.

Differentiation of mouse embryonic stem cells after RNA interference-mediated silencing of OCT4 and Nanog.

RNA interference (RNAi) holds great promise as a tool to study the basic biology of stem cells or to direct differentiation in a specific manner. Barriers to achieving efficient and specific gene silencing in RNAi experiments include limitations in transfection efficiency and in the efficacy and specificity of RNAi silencing effectors. Here, we combine methods of efficient lipid-mediated delivery with chemically modified RNAi compounds to silence genes related to pluripotency, in order to direct differentiation of mouse embryonic stem cells. After transfection of embryonic stem cells with OCT4- or Nanog-targeted RNAi compounds, levels of OCT4 or Nanog transcript and protein were reduced accordingly. Reduction in OCT4 expression correlated with induction of trophectoderm genes Cdx2, Hand1, and PL-1, with formation of cells with trophoblast giant cell phenotype after 6 days. Reduction in Nanog expression correlated with induction of extraembryonic endoderm genes GATA4, GATA6, and laminin B1, with subsequent generation of groups of cells with parietal endoderm phenotype. Our results indicate that transient inhibition of OCT4 or Nanog by RNAi compounds is sufficient to induce differentiation toward extraembryonic lineages, which supports the model that these transcription factors function in a dose-dependent manner to influence cell fate.

Operator-interactive method for simultaneous measurement of left and right ventricular volumes and ejection fraction by tomographic electrocardiography-gated blood pool radionuclide ventriculography.

BACKGROUND: A method that uses single photon emission computed tomography (SPECT) equilibrium radionuclide angiocardiography (ERNA) to measure right ventricular (RV) and left ventricular (LV) volumes (in milliliters) and ejection fraction (EF) is described. METHODS AND RESULTS: We recorded 35 paired SPECT ERNA and electron beam computed tomography (EBCT) cardiac studies in 27 patients; for comparison with EBCT, a method for measurement of RV and LV volumes and EF with SPECT ERNA was developed in 18 paired studies and was validated and assessed for reproducibility in 17. Validation indicated that SPECT ERNA and EBCT were similar for measurement of RV volume (end-systolic and end-diastolic volumes in a combined analysis) and EF (180+/-74 mL vs 182+/-80 mL and 0.44+/-0.11 vs 0.43+/-0.11, respectively) and for measurement of LV volume and EF (88+/-36 mL vs 84+/-43 mL and 0.53+/-0.081 vs 0.59+/-0.07, respectively). The SPECT ERNA method was quite reproducible. CONCLUSIONS: RV and LV volumes and EF can be measured readily via SPECT ERNA.

Combined systolic and diastolic dysfunction in the presence of preserved left ventricular ejection fraction.

BACKGROUND: Heart failure with preserved left ventricular ejection fraction (LVEF) suggests isolated diastolic dysfunction. AIM: The purpose of this study was to determine if systolic and diastolic dysfunction occurred with preserved LVEF. METHODS: Equilibrium resting radionuclide ventriculograms from 439 patients with an LVEF >/=0.50 were used to determine LV peak filling rate (PFR) and peak ejection rate (PER) in end-diastolic volumes per second and LV end-systolic volume (ml). Patients with low-normal (n=147; range, 0.50-0.58; mean+/-S.D., 0.53+/-0.02), intermediate-normal (161, 0.59-0.64, 0.61+/-0.02), and high-normal (131, 0.65-0.94, 0.72+/-0.06) LVEF were compared. RESULTS: From low-normal to intermediate-normal to high-normal LVEF, LV end-systolic volume decreased (93+/-36, 71+/-33, 43+/-26, respectively, P<0.0001), PFR increased (2.31+/-0.74, 2.58+/-0.74, 3.15+/-0.94, P<0.0001), PER increased (-2.78+/-0.50, -3.13+/-0.47, -3.83+/-0.84, P<0.0001), the percentages of patients with abnormal PFR decreased (66, 56, 40, P<.0001), and the percentage with abnormal PER decreased (47, 14, 5, P<0.0001). Of 193 patients with preserved LVEF and abnormally low PFR, 65 (34%) had abnormally low PER. CONCLUSIONS: The results indicate that a preserved LVEF was often associated with LV systolic dysfunction (enlarged LV end-systolic volume and low PER) and LV diastolic dysfunction (decreased PFR).

Association of the PURSUIT risk score with predischarge ejection fraction, angiographic severity of coronary artery disease, and mortality in a nonselected, community-based population with non-ST-elevation acute myocardial infarction.

BACKGROUND: The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) risk score was derived from the PURSUIT trial population for 30-day mortality prediction. METHODS: The PURSUIT risk score was calculated for 337 consecutive Olmsted County residents with non-ST-elevation acute myocardial infarction admitted to the coronary care unit of our institution from 1988 through 1998. Predischarge ejection fraction (EF) measurement was available for 246 patients (73%). After excluding patients with prior coronary artery bypass graft surgery (n = 42), 219 patients (65%) had coronary angiography within 30 days of admission. Mortality at 30 days was 8.9%. Among 30-day survivors, mortality at 1 year was 7.9%. RESULTS: Mean age was 70 +/- 13 years, and 37% of patients were women. Mean predischarge EF was 52% +/- 16%. Patients with higher PURSUIT risk score had lower EF (P <.001). Three-vessel (> or =70% stenosis in all 3 coronary arteries) or left main (> or =50% stenosis) coronary artery disease was present in 60 of 219 patients (27%) who had coronary angiography. Higher PURSUIT risk score was associated with greater likelihood of 3-vessel or left main disease (P <.001). The PURSUIT risk score had very good predictive accuracy for both early (30-day, C-statistic = 0.78) and late (30-day to 1-year, C-statistic = 0.77) mortality. CONCLUSIONS: The PURSUIT risk score correlates with EF, angiographic severity of coronary artery disease, and short- and long-term mortality of nonselected patients with non-ST-elevation acute myocardial infarction.

Usefulness of QRS duration in the absence of bundle branch block as an early predictor of survival in non-ST elevation acute myocardial infarction.

To determine whether an increased QRS duration in the absence of bundle branch block (BBB) on the presenting electrocardiogram of patients with acute myocardial infarction (AMI) is associated with decreased survival, we retrospectively reviewed 781 consecutive patients admitted to the coronary care unit of our institution with AMI without BBB between 1988 and 1998. In patients with ST elevation AMI (n = 412), the groups with QRS duration > or =100 ms and <100 ms had similar survival. Conversely, in patients with non-ST elevation AMI (n = 369), in-hospital, 1-, 3-, and 5-year survival was 84.4%, 75.6%, 66.7%, and 52.2%, respectively, in the group with QRS > or =100 ms compared with 95.4%, 89.2%, 83.8%, and 74.3%, respectively, in the group with QRS <100 ms (p <0.01, log-rank test). In patients with non-ST elevation AMI, those with QRS duration > or =100 ms were more likely to be men, to have had a prior AMI that healed, to be in Killip class II, III, or IV, and to have lower ejection fraction than patients with QRS duration <100 ms. After adjusting for age, sex, prior AMI or stroke, heart rate, and Killip class on admission, QRS duration > or =100 ms was independently associated with in-hospital and overall mortality in patients with non-ST elevation AMI. QRS duration > or =100 ms in the absence of BBB is an independent predictor of increased mortality in patients with non-ST elevation AMI.