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PubMedDate not supplied

Risk stratification after acute myocardial infarction in the reperfusion era.

Historically, risk stratification for survivors of acute myocardial infarction (AMI) has centered on 3 principles: assessment of left ventricular function, detection of residual myocardial ischemia, and estimation of the risk for sudden cardiac death. Although these factors still have important prognostic implications for these patients, our ability to predict adverse cardiac events has significantly improved over the last several years. Recent studies have identified powerful predictors of adverse cardiac events available from the patient history, physical examination, initial electrocardiogram, and blood testing early in the evaluation of patients with AMI. Numerous studies performed in patients receiving early reperfusion therapy with either thrombolysis or primary angioplasty have emphasized the importance of a patent infarct related artery for long-term survival. The predictive value of a variety of noninvasive and invasive tests to predict myocardial electrical instability have been under active investigation in patients receiving early reperfusion therapy. The current understanding of the clinically important predictors of clinical outcomes in survivors of AMI is reviewed in this article.

Death, Sudden, Cardiac↗
PubMed2001

Clinical and molecular stratification of disease risk in medulloblastoma.

The accurate assessment of disease risk among children with medulloblastoma remains a major challenge to the field of paediatric neuro-oncology. In the current study we investigated the capacity of molecular abnormalities to increase the accuracy of disease risk stratification above that afforded by clinical staging alone. 41 primary medulloblastoma tumour samples were analysed for ErbB2 receptor expression using immunohistochemistry, and for aberrations of chromosome 17 and amplification of the MYC oncogene using fluorescence in situ hybridisation. The ErbB2 receptor and deletion of 17p were detected in 80% and 49% of tumours, respectively. 17p loss occurred either in isolation (20%), or in association with gain of 17q (29%), compatible with an isochromosome of 17q. Amplification of MYC was detected in only 2 tumours. Significant prognostic factors included, 'metastatic disease' (P = 0.0006), 'sub-total tumour resection' (P = 0.007), 'high ErbB2 receptor expression' (P = 0.003) and 'isolated 17p loss' (P = 0.003). Combined analysis of clinical and molecular factors enabled greater resolution of disease risk than clinical factors alone, identifying a sub-population of patients with particularly favourable disease outcome. These data support the hypothesis that a combination of clinical and molecular factors may afford a more reliable means of assigning disease risk in patients with medulloblastoma, thereby providing a more accurate basis for targeting therapy in children with this disease.

Adolescent↗
PubMed2002

Risk stratification applied to CAST registry data: combining 9 predictors. Cardiac Arrhythmia Suppression Trial.

Over 200,000 people in the United States die of sudden cardiac death (SCD) every year. Although many of these deaths occur in asymptomatic individuals, the vast majority of deaths occur in people who are under care for existing coronary heart disease. Implantable cardioverter/defibrillators (ICDs) have been shown in several randomized trials to be effective in prolonging lives of those at high risk for sudden cardiac death, but the criteria used in these trials and the ACC/AHA consensus guidelines would cover only a minority of patients. Developing methods to assign risk to individual patients without prior SCD events could promote the use of this life-saving therapy in those with especially high risk. Given sufficient physiologically relevant measurements from electrocardiogram analysis, clinical assessment, and demographic status, multivariate statistical methods for predicting survival can be used to combine many predictors of risk and calculate the risk for an individual patient. A survival analysis using Cox regression on data from the Cardiac Arrhythmia Suppression Trial (CAST) illustrates this concept. Patient age, sex, ejection fraction, smoking history, and prior myocardial infarction history, along with the frequency of premature beats and the presence of runs of ventricular tachycardia on Holter monitoring and the time from the index myocardial infarction to the baseline Holter and to recruitment into CAST were combined in a multivariate predictor derived from the Cox regression; this predictor significantly outperforms the individual predictors. A proposed test based on this predictor would identify as positive 7% of the CAST registry, with an average risk of death among the positives of 47%; 20% of those dead at 2 years would be positive. With improved component measurements, this approach has the potential for significantly improving risk stratification for the prevention of SCD.

Age Factors↗
PubMed2002

Risk stratification scores for predicting mortality in coronary artery bypass surgery.

BACKGROUND: Four risk-stratification scores (RSSs - Euro, French, CCS/Higgins, Parsonnet) were tested as predictors of mortality in coronary artery bypass grafting (CABG) surgery. METHODS: From March to April 2000, the perioperative courses of 245 consecutive CABG patients were compared to the predictions according to the RSSs. Sensitivity and specificity were determined with receiver operating characteristics (ROC) curves. RESULTS: CCS/Higgins uses the most easily acquired patient data, and rates emergency conditions as high-risk. Euro focuses on advanced age and septal rupture. French uses the smallest number of patient parameters and rates rare critical situations as high-risk. Parsonnet is partially based on the physician's subjective assessment of a "catastrophic state," making the scoring arbitrary. All RSSs gave similar (not significant) areas under the ROC curves regarding mortality (Euro 0.826 +/- 0.080, French 0.783 +/- 0.094, CCS/Higgins 0.820 +/- 0.060, Parsonnet 0.831 +/- 0.042). Predicted risk levels for the 11 patients who died differed between the RSSs--Higgins placed these patients in 3 of 5 risk levels with ascending distribution. The other RSSs placed these patients in the highest risk level except for one and two patients, respectively, who were placed in the lowest Euro and French risk level. Euro and Parsonnet placed about half of all patients with non-lethal outcome in the highest risk level. CONCLUSIONS: All RSSs satisfactorily estimated the group risk for mortality. No RSS expressed sufficient validity to predict individuals with lethal outcome. In clinical use, CCS/Higgins proved the most practicable.

Adult↗
PubMedDate not supplied

[Risk stratification in medulloblastoma: screening for molecular markers].

BACKGROUND: The present study evaluates molecular markers for patients at risk of poor or no response to medulloblastoma. The aim of the study is to optimize therapy stratification. PATIENTS AND METHODS: 69 snap-frozen medulloblastoma samples were examined. C-MYC amplification was determined by fluorescence in situ hybridisation (FISH) analysis. Methylation specific PCR revealed the level of promoter methylation status of the tumor suppressor genes CASP8 (Caspase 8), TIMP3, CDH1 (E-Cadherin), CDKN2A (p16) and MGMT. Expression of GAS7 was evaluated by RT-PCR. RESULTS: C-MYC amplification: 4/69 tumors displayed high level amplification; 53/69 tumors displayed low level (< 4 copies) or no amplification; 12/69 samples were not predictive. In patients with c-MYC amplification a tendency towards unfavorable outcome was observed (p = 0.3). Promoter methylation status: CASP8: in 36/40 tumors methylated; TIMP3: 1/38 methylated; MGMT 0/44 methylated; CDKN2A: 1/46 methylated; E-cadherin 3/36 methylated; no association between methylation status and clinical outcome. GAS7: Detection of specific RNA in 20/29 medulloblastoma samples. CONCLUSION: No significant association between amplification of c-MYC and clinical outcome was observed. Promoter methylation of tumor suppressor genes is non-randomly distributed with a high level of methylation of CASP8. Recent studies show that silencing of CASP8 by methylation could be overcome by interferon gamma providing a possible therapeutic mechanism. GAS7 was shown to be a marker of mature neuronal cells with potential antitumorigenic capacity in neuronal tumors. In medulloblastoma 20/29 of the tumors examined express GAS7. Therefore a tumor suppressing function of GAS7 is improbable.

Biomarkers, Tumor↗
PubMed2006

[Preoperative stratification of risks in patients with disorders of the cardiovascular system].

Disorders of the cardiovascular system are among the most important accompanying diseases in operative medicine. These diseases increase the perioperative risk; the risk is assessed on the basis of the case history and tolerance of the patient as well as the extent and invasiveness of the surgical intervention. Depending on the results of this stratification further examination and therapy may be necessary. The aim of these mainly preventative measures is the highest possible preoperative hemodynamic stability. Besides pharmacological prevention, a therapy for hypertension or ischemia belongs among these measures. The selected anesthesia process must guarantee and efficient prevention of pain.

Anesthesia↗
PubMed2003

Risk stratification in the long-QT syndrome.

BACKGROUND: Mutations in potassium-channel genes KCNQ1 (LQT1 locus) and KCNH2 (LQT2 locus) and the sodium-channel gene SCN5A (LQT3 locus) are the most common causes of the long-QT syndrome. We stratified risk according to the genotype, in conjunction with other clinical variables such as sex and the length of the QT interval. METHODS: We evaluated 647 patients (386 with a mutation at the LQT1 locus, 206 with a mutation at the LQT2 locus, and 55 with a mutation at the LQT3 locus) from 193 consecutively genotyped families with the long-QT syndrome. The cumulative probability of a first cardiac event, defined as the occurrence of syncope, cardiac arrest, or sudden death before the age of 40 years and before the initiation of therapy, was determined according to genotype, sex, and the QT interval corrected for heart rate (QTc). Within each genotype we also assessed risk in the four categories derived from the combination of sex and QTc (<500 msec or > or =500 msec). RESULTS: The incidence of a first cardiac event before the age of 40 years and before the initiation of therapy was lower among patients with a mutation at the LQT1 locus (30 percent) than among those with a mutation at the LQT2 locus (46 percent) or those with a mutation at the LQT3 locus (42 percent) (P<0.001 by Fisher's exact test). Multivariate analysis showed that the genetic locus and the QTc, but not sex, were independent predictors of risk. The QTc was an independent predictor of risk among patients with a mutation at the LQT1 locus and those with a mutation at the LQT2 locus but not among those with a mutation at the LQT3 locus, whereas sex was an independent predictor of events only among those with a mutation at the LQT3 locus. CONCLUSIONS: The locus of the causative mutation affects the clinical course of the long-QT syndrome and modulates the effects of the QTc and sex on clinical manifestations. We propose an approach to risk stratification based on these variables.

Adult↗
PubMed2003

Risk stratification and safe administration of propofol by registered nurses supervised by the gastroenterologist: a prospective observational study of more than 2000 cases.

BACKGROUND: Conscious sedation is standard for GI endoscopy. Propofol increasingly is used as an alternative drug to avoid unwanted effects of the commonly used benzodiazepines. Although propofol in the hands of nonanesthesiologists is still controversial, this study characterized the safety profile of propofol administered by nurses under supervision of the gastroenterologist. METHODS: All patients undergoing any endoscopic procedure between September 2000 and December 2001 in the gastroenterology department of an academic tertiary medical center were eligible for inclusion in this prospective observational study. Sedation was voluntary. Demographic data, type of endoscopic procedure, and clinical features were recorded. A structured personal history led to a 5-class risk stratification based on the criteria of the American Society of Anesthesiologists. A total of 3475 procedures were performed in 2574 patients using propofol administered by registered nurses. RESULTS: No major complications occurred because of the use of propofol, but overall decreases in the mean values for oxygen saturation (-2%), arterial pressure (-18%), and pulse rate (-10%) were observed. Severe respiratory depression requiring intervention occurred in less than 0.3% of all patients given propofol. CONCLUSION: The administration of propofol by registered nurses, with careful monitoring under the supervision of the gastroenterologist, is safe for conscious sedation during GI endoscopic procedures.

Aged↗
PubMed2000

Arrhythmia risk stratification in idiopathic dilated cardiomyopathy based on echocardiography and 12-lead, signal-averaged, and 24-hour holter electrocardiography.

BACKGROUND: To date, considerable controversy exists regarding noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy (IDC). Methods and Results Between 1992 and 1997, 202 patients with IDC without a history of sustained ventricular tachycardia (VT) underwent echocardiography, signal-averaged electrocardiogram (ECG), and 24-hour Holter ECG in the absence of antiarrhythmic drugs. During 32 +/- 15 months of prospective follow-up, major arrhythmic events, including sustained VT, ventricular fibrillation, or sudden death, occurred in 32 (16%) of 202 patients. After adjusting for baseline medical therapy and antiarrhythmic therapy during follow-up, multivariate Cox regression analysis identified a left ventricular (LV) end-diastolic diameter >/=70 mm and nonsustained VT on Holter as the only independent arrhythmia risk predictors. The combination of an LV end-diastolic diameter >/=70 mm and nonsustained VT was associated with a 14. 3-fold risk for future arrhythmic events (95% confidence interval 2. 3-90). To further elucidate the prognostic value of LV ejection fraction, multivariate Cox analysis was repeated with ejection fraction forced to remain in the model. In the latter model, an ejection fraction </=30% combined with nonsustained VT on Holter was found to be a significant arrhythmia risk predictor with a relative risk of 14.6 (95% confidence interval 2.2-97). CONCLUSIONS: The combination of an LV end-diastolic diameter >/=70 mm and nonsustained VT on Holter, and the combination of LV ejection fraction </=30% and nonsustained VT on Holter, identify a subgroup of patients with IDC with a 14-fold risk for subsequent arrhythmic events. These findings have important implications for the design of future studies evaluating the role of prophylactic defibrillator therapy in patients with IDC.

Adolescent↗
PubMed2000

Very early risk stratification after thrombolytic therapy with a bedside myoglobin assay and the 12-lead electrocardiogram.

BACKGROUND: Available clinical criteria to estimate prognosis in patients with evolving ST-segment elevation myocardial infarction do not consider the impact of reperfusion therapy and do not incorporate measurement of baseline levels of cardiac serum markers. We evaluated the combination of a baseline myoglobin assay and early (60- to 90-minute) ST resolution for risk stratification after ST-segment elevation myocardial infarction. METHODS: In a prospective substudy of the Intravenous nPA for Treatment of Infarcting Myocardium Early-II (InTIME-II) trial carried out in 2079 patients, a rapid qualitative assay for myoglobin was performed immediately before thrombolysis. Serial 12-lead electrocardiograms were performed at baseline and 60 to 90 minutes after thrombolysis. ST resolution was categorized as complete (>/=70%), partial (30% to <70%), or none (<30%). RESULTS: Mortality rate at 30 days was 3.3% in the 905 patients with a negative baseline myoglobin assay versus 8.9% in the 527 patients with a positive assay (P <.0001). Mortality rate was lowest (2.4%) among the 614 patients with complete ST resolution, intermediate (4.9%) among the 512 patients with partial ST resolution, and highest (8.1%) among the 540 patients with no ST resolution (P <.0001 for trend). In a logistic regression model incorporating other baseline predictors of 30-day mortality rate, both a positive myoglobin assay (relative risk 1.98, 95% confidence interval 1.00-3.90) and ST resolution <70% (relative risk 2.86, 95% confidence interval 1.22-6.69) were independently associated with increased mortality rate. At 30 days, mortality rate was 0.4% among patients with a negative myoglobin assay and complete ST resolution, 4.8% among patients with either a positive myoglobin assay or ST resolution <70%, and 9.6% among those with both a positive myoglobin ratio and ST resolution <70% (P <.001 for trend). CONCLUSIONS: Within 90 minutes after administering thrombolytic therapy for acute myocardial infarction, clinicians can determine the risk for death at the patient's bedside with a hand-held myoglobin assay and 2 serial 12-lead electrocardiograms. A strategy using these 2 simple, rapid, and inexpensive tests may facilitate triage after thrombolytic therapy.

Adult↗
PubMed2002

Ventilatory response to exercise improves risk stratification in patients with chronic heart failure and intermediate functional capacity.

BACKGROUND: Peak oxygen consumption (VO2) has an important prognostic role in chronic heart failure (CHF), but its discriminatory power is limited in patients with intermediate exercise capacity (peak VO2 between 10-18 mL/kg/min). Thus, supplementary exertional indexes are greatly needed. METHODS: Six hundred patients with CHF with left ventricular ejection fraction (LVEF) < or = 40% who performed a symptom-limited cardiopulmonary exercise testing were screened and followed up for 780 +/- 450 days. RESULTS: Eighty-seven patients had major cardiac events (77 cardiac deaths and 10 urgent heart transplantations). Multivariate analysis revealed the rate of increase of minute ventilation per unit of increase of carbon dioxide production (VE/VCO2 slope) (chi2, 79.3, P <.0001), LVEF (chi2, 24.6, P <.0001), and peak VO2 (chi2, 9.4, P <.0001) as independent and additional predictors of major cardiac events. VE/VCO2 slope was the strongest independent predictor of outcome (chi2, 20.9, P =.0001) in patients with intermediate peak VO2 (n = 403), and the best cutoff value was 35 (chi2, 25.8; relative risk = 3.2, 95% CI 2.0-5.1, P <.0001). Total mortality rate was 30% in patients with VE/VCO2 slope > or = 35 (n = 103, 26%) and 10% in those with VE/VCO2 slope <35 (n = 300, 74%) (P <.0001). Patients with VE/VCO2 slope > or = 35 had a similar total mortality rate to those with peak VO2 < or = 10 mL/kg/min (30% vs 37%, P not significant). CONCLUSIONS: A rational and pragmatic risk stratification process with symptom-limited cardiopulmonary exercise testing in CHF should include both peak VO2 and VE/VCO2 slope, the latter index effectively predicting outcome in almost one fourth of patients with intermediate exercise capacity.

Carbon Dioxide↗
PubMed2003

The problem of decompensated heart failure: nomenclature, classification, and risk stratification.

Despite its high prevalence and significant rates of associated morbidity and mortality, the syndrome of decompensated heart failure remains poorly defined and vastly understudied. Few high-quality epidemiologic studies, randomized controlled trials, or published guidelines are available to guide the management of this complex disease. In addition, there is no consensus definition of the clinical problem that it presents, no agreed upon nomenclature to describe its clinical features, and no recognized classification scheme for its patient population; all of which has contributed to the lack of therapeutic development in this critical arena of cardiovascular disease. This review outlines the scope of the problem and proposes a system of nomenclature and classification sufficiently simple for general acceptance among clinicians while still encompassing the heterogeneity of the patient population. It also defines the current understanding of strategies for risk stratification in the setting of decompensated heart failure.

Acute Disease↗
PubMedDate not supplied

Risk stratification in patients with remote prior myocardial infarction using rest-stress myocardial perfusion SPECT: prognostic value and impact on referral to early catheterization.

BACKGROUND: Little is known about the prognostic value of myocardial perfusion single photon emission computed tomography (SPECT) in patients with remote prior myocardial infarction (MI). METHODS AND RESULTS: We identified 1413 consecutive patients with remote prior MI who underwent rest-stress myocardial perfusion SPECT. Semiquantitative visual analysis of 20 SPECT segments was used to define the summed stress, rest, and difference scores. The number of non-reversible segments was used as an index of infarct size. During follow-up (>or=1 year), 118 hard events occurred: 64 cardiac deaths (CDs) and 54 recurrent MIs. Annual CD and hard event rates increased significantly as a function of SPECT abnormality. For summed stress scores less than 4, 4 to 8, 9 to 13, and more than 13, the annual CD rates were 0.4%, 0.9%, 1.7%, and 3.5%, respectively (P =.002). Patients with small MI (<4 non-reversible segments) and no or mild ischemia (summed difference score or=4 non-reversible segments) had moderate to high annual CD rates (3.7%-6.6%) regardless of the extent of ischemia. Nuclear testing added incremental prognostic information to pre-scan information. Compared with a strategy in which all patients are referred to catheterization, a strategy that referred only those patients with a risk for CD of greater than 1% by myocardial perfusion SPECT resulted in a 41.6% cost savings. CONCLUSIONS: Myocardial perfusion SPECT adds incremental value to pre-scan information and is highly predictive and cost-efficient in the risk stratification of patients with remote prior MI. Patients with normal or mildly abnormal scan results or small MI in combination with absent or mild ischemia have a low risk for CD.

Adenosine↗
PubMed2001

Cardiac risk stratification for postmyocardial infarction dental patients.

Traditional dental management guidelines of myocardial infarction survivors mandate a 6-month waiting period before elective treatment can be considered. Technological advances in cardiac disease diagnosis, management, and revascularization treatment may make this older mandatory 6-month waiting period obsolete. The purposes of this literature review are to provide an overview of the historical development of cardiac risk stratification and discuss current developments and guidelines in cardiac risk assessment. We hope that this review and update will stimulate the development of updated dental guidelines for treating the cardiac patient.

Clinical Protocols↗
PubMed2006

Directly observed reversible shape changes and hemoglobin stratification during centrifugation of human and Amphiuma red blood cells.

This paper describes changes that occur in human and Amphiuma red blood cells observed during centrifugation with a special microscope. Dilute suspensions of cells were layered, in a centrifuge chamber, above an osmotically matched dense solution, containing Nycodenz, Ficoll, or Percoll (Pharmacia) that formed a density gradient that allowed the cells to slowly settle to an equilibrium position. Biconcave human red blood cells moved downward at low forces with minimum wobble. The cells oriented vertically when the force field was increased and Hb sedimented as the lower part of each cell became bulged and assumed a "bag-like" shape. The upper centripetal portion of the cell became thinner and remained biconcave. These changes occurred rapidly and were completely reversible upon lowering the centrifugal force. Bag-shaped cells, upon touching red cells in rouleau, immediately reverted to biconcave disks as they flipped onto a stack. Amphiuma red cells displayed a different type of reversible stratification and deformation at high force fields. Here the cells became stretched, with the nucleus now moving centrifugally, the Hb moving centripetally, and the bottom of the cells becoming thinner and clear. Nevertheless, the distribution of the marginal bands at the cells' rim was unchanged. We conclude that centrifugation, per se, while changing a red cell's shape and the distribution of its intracellular constituents, does so in a completely reversible manner. Centrifugation of red cells harboring altered or missing structural elements could provide information on shape determinants that are still unexplained.

Animals↗
PubMed2004

The DP-1 transcription factor is required for keratinocyte growth and epidermal stratification.

The epidermis is a stratified epithelium constantly replenished through the ability of keratinocytes in its basal layer to proliferate and self-renew. The epidermis arises from a single-cell layer ectoderm during embryogenesis. Large proliferative capacity is central to ectodermal cell and basal keratinocyte function. DP-1, a heterodimeric partner of E2F transcription factors, is highly expressed in the ectoderm and all epidermal layers during embryogenesis. To investigate the role of DP-1 in epidermal morphogenesis, we inhibited DP-1 activity through exogenous expression of a dominant-negative mutant (dnDP-1). Expression of the dnDP-1 mutant interferes with binding of E2F/DP-1 heterodimers to DNA and inhibits DNA replication, as well as cyclin A mRNA and protein expression. Chromatin immunoprecipitation analysis demonstrated that the cyclin A promoter is predominantly bound in proliferating keratinocytes by complexes containing E2F-3 and E2F-4. Thus, the mechanisms of decreased expression of cyclin A in the presence of dnDP-1 seem to involve inactivation of DP-1 complexes containing E2F-3 and E2F-4. To assess the consequences on epidermal morphogenesis of inhibiting DP-1 activity, we expressed dnDP-1 in rat epithelial keratinocytes in organotypic culture and observed that DP-1 inhibition negatively affected stratification of these cells. Likewise, expression of dnDP-1 in embryonic ectoderm explants produced extensive disorganization of subsequently formed epidermal basal and suprabasal layers, interfering with normal epidermal formation. We conclude that DP-1 activity is required for normal epidermal morphogenesis and ectoderm-to-epidermis transition.

Adenoviridae↗
PubMed2005

Hsp27 expression coincides with epidermal stratification during human epidermal morphogenesis.

Heat shock protein 27 (Hsp27), apart from its protective function in response to stress, is implicated in the regulation of cell growth, differentiation and apoptosis. Data on the expression of Hsp27 in the developing human epidermis are sparse and partially conflicting. Thus, the purpose of the present study was to investigate Hsp27 expression during the morphogenesis of human epidermis. Skin biopsies and dispase-separated epidermal sheets obtained from 7 human embryos (7 and 8 weeks estimated gestational age, EGA), from 79 human fetuses (9-23 weeks EGA) and from 10 healthy adult volunteers were investigated by immunohistochemistry and Western blotting, respectively. The earliest detection of Hsp27 expression was found by immunohistochemistry at the 12th week EGA (basal and intermediate layer) and by Western blotting at the 9th week EGA. From the 16th to the 23rd week EGA immunoreactivity was not detectable in the basal layer, whereas in the overlying layers it revealed a differentiation-related pattern. The simultaneous onset of epidermal stratification and Hsp27 expression (9th week EGA) and the alterations of the latter in the subsequent stages of development, suggest that this stress protein may be involved in the molecular events underlying human epidermal morphogenesis.

Adult↗