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PubMed2002

Outcome after abnormal exercise echocardiography for patients with good exercise capacity: prognostic importance of the extent and severity of exercise-related left ventricular dysfunction.

OBJECTIVES: We sought to define the prognostic implications of the extent and severity of exercise echocardiographic abnormalities in patients with good exercise capacity. BACKGROUND; The exercise capacity of patients with known or suspected coronary artery disease (CAD) is of prognostic importance, as is the extent of exercise-related left ventricular (LV) hypoperfusion or dysfunction. METHODS: We examined the outcomes of 1,874 patients with known or suspected CAD (mean age 64 +/- 10 years, 64% men) who had good exercise capacity (> or = 5 metabolic equivalents [METs] for women, > or = 7 METs for men) but abnormal exercise echocardiograms and analyzed the potential association between clinical, exercise and echocardiographic variables and subsequent cardiac events. RESULTS: Multivariate predictors of time to cardiac death or nonfatal myocardial infarction (MI) were diabetes mellitus (risk ratio [RR] 1.88; 95% confidence interval [CI] 1.2 to 3.0), history of MI (RR 2.44; 95% CI 1.6 to 3.6) and an increase or no change in LV end-systolic size in response to exercise (RR 1.61; 95% CI 1.1 to 2.5). Using echocardiographic variables that were of incremental prognostic value, we were able to stratify the cardiac risk of the study population; cardiac death or nonfatal MI rate per person-year of follow-up was 1.6% for patients who had a decrease in LV end-systolic size in response to exercise (n = 1,330) and 1.2% for patients who did not have any severely abnormal LV segments immediately after exercise (n = 868). CONCLUSIONS: In patients with good exercise capacity, echocardiographic descriptors of the extent and severity of exercise-related LV dysfunction were of independent and incremental prognostic value. Stratification of patients into low- and higher risk subgroups was possible using these exercise echocardiographic characteristics.

Aged↗
PubMed2003

Troponin: an important prognostic marker and risk-stratification tool in non-ST-segment elevation acute coronary syndromes.

Over the past decade, there has been a progressive evolution of cardiac marker testing in patients with acute coronary syndromes (ACS). This has not only resulted in a dramatic shift in how we view the diagnosis of myocardial infarction (MI), but it has also extended the role of cardiac marker testing into risk stratification and guidance of treatment decisions. By the year 2000, the development of highly sensitive and cardiac-specific troponin assays had resulted in a consensus change in the definition of MI, placing increased emphasis on cardiac-marker testing with troponins as the new gold standard. Furthermore, and perhaps more importantly, the role of the troponins as superior markers of subsequent cardiac risk in ACS patients became firmly established. Most recently, the supportive role of these markers in identifying patients with ACS who may derive particular benefit from potent anti-thrombotic and anti-platelet therapy or early invasive treatment strategies has been demonstrated. This paper will review the evolution of these important roles of troponin testing for risk stratification in ACS.

Biomarkers↗
PubMed2001

Alpha-interferon maintenance treatment is associated with improved survival after high-dose treatment and autologous stem cell transplantation in patients with multiple myeloma: a retrospective registry study from the European Group for Blood and Marrow Transplantation (EBMT).

The purpose of this study was to evaluate the effect of alpha-IFN maintenance treatment after autologous stem cell transplantation (ASCT) for multiple myeloma in a retrospective registry analysis. 473 patients with multiple myeloma who received IFN maintenance treatment ASCT were compared with 419 patients who did not receive IFN-treatment. Patients who were evaluable for response and in complete or partial remission at 6 months after ASCT were eligible, after excluding patients with graft failure. Cox proportional hazards assumptions were checked and handled by stratification. The prognostic variables unevenly distributed between the two groups were statistically corrected for in the Cox analysis. 391 patients reached complete remission (CR) after ASCT (203 in the IFN group and 188 in the no-IFN group) and 501 were in partial remission (PR, IFN 270, no-IFN 231). Overall survival (OS) and progression-free survival (PFS) were significantly better in the IFN-group (OS, 78 vs 47 months, P = 0.007, and PFS, 29 vs 20 months, P = 0.006, respectively). The difference in OS and PFS was most strongly pronounced in the PR patients. 209 patients have died (IFN, 84; no-IFN, 125). Progressive myeloma was the cause of death in 94% of the IFN-treated patients and in 83% of the no-IFN group (P = NS). Thus, IFN maintenance treatment after ASCT was associated with better OS and PFS. Treatment seemed to be most beneficial in patients who did not achieve CR. The difference in median survival was as long as 2.5 years, and although part of this difference is attributable to differences in other prognostic factors, it might justify possible differences in quality-of-life due to adverse effects of interferon treatment.

Adolescent↗
PubMed2002

Arrhythmic risk stratification after myocardial infarction using ambulatory electrocardiography signal averaging.

Ambulatory ECG had been proposed to examine the amplified high resolution signal-averaged electrocardiogram (SAECG). Clinical investigations are required to confirm the predictive value of such a high resolution technique in arrhythmic risk stratification. The prognostic value of ambulatory Holter SAECG was evaluated in 108 postinfarction patients for the purpose of predicting the occurrence of serious arrhythmic (SARR) events (sudden cardiac death [SCD], VT, or VF) in comparison with classical real-time SAECG. During the 42+/-8 months of follow-up, the sudden cardiac death mortality was 4.6% (five deaths), six (5.6%) patients had VT, and one (0.9%) VF. QRSd was found to be the most predictive parameter using ROC curves analysis for SAAR + outcome (W = 0.833 and W = 0.803 for 25-250 Hz and 40-250 Hz filters, respectively) followed by RMS (W = 0.766 and W = 0.721) and LAS (W = 0.759, W = 0.709) (all P < 0.01). Abnormal Holter SAECG for 25 and 40-Hz LP filter were significant predictors of SARR+ by log-rank test (P < 0.01, P < 0.05, respectively). This study confirms that valuable prognostic information can be obtained from the ambulatory high resolution ECG technique and that Holter SAECG may predict arrhythmic risk in a postinfarction population.

Action Potentials↗
PubMed2000

Outcome of acute renal failure following surgical repair of ruptured abdominal aortic aneurysms.

OBJECTIVES: to establish the mortality of ARF following surgical repair of ruptured abdominal aortic aneurysms (AAAs) and to identify clinical variables which might assist in predicting outcome. DESIGN, MATERIALS AND METHODS: all cases of ARF complicating repair of ruptured AAAs treated at Leicester General Hospital between 1984 and 1996 were identified in a retrospective study based on review of clinical records. The main outcome measures were overall mortality, duration of hospital treatment and renal function in survivors. RESULTS: in 65 cases identified, overall hospital mortality was 75%. Six patients did not receive RRT, since their clinical state was judged irreversible; all died. Of the 16 survivors, 11 were left with irreversible renal impairment and one patient required maintenance dialysis. Over half of the survivors had died at 5 years>> follow-up. Non-survivors had more vascular disease (p=0.048), required more surgery during AAA repair (p=0.042) and were more likely to have developed multiple organ failure (p=0.01). A clinical severity score based on these three variables allowed stratification into prognostic groups. CONCLUSIONS: ARF following surgical repair of ruptured AAA has an overall hospital mortality of 75%. A clinical severity score, calculated at the time dialysis was considered, may assist in prediction of outcome.

APACHE↗
PubMed1995

Identification of subsets of neuroblastomas by combined histopathologic and N-myc analysis.

BACKGROUND: Neuroblastomas show different histopathologic phenotypes, and the tumor cells can carry normal or multiple copies of the N-myc proto-oncogene (MYCN). Studies of the N-myc gene and histopathology of untreated primary neuroblastomas have demonstrated that both these factors are important in risk assessment. PURPOSE: Our purpose was to determine if there are any associations between N-myc gene copy number, histopathologic features, clinical stage, and progression-free survival (PFS) and if joint analyses of histopathology and N-myc gene copy number improve risk assessment. METHODS: The histopathologic phenotype and N-myc gene copy number were determined for 232 biopsy/surgery specimens obtained from untreated primary neuroblastoma patients. Tumors were classified as having favorable or unfavorable histology on the basis of Schwannian stroma (rich versus poor), neuroblastic differentiation (differentiating versus undifferentiated), and mitosis-karyorrhexis (fragmenting nucleus) index (MKI; high, intermediate, or low) in the context of age at diagnosis (Shimada classification). N-myc gene amplification was considered significant when the gene copy number was at least 10-fold higher than normal as determined by Southern blot analysis. Otherwise, tumors were classified as nonamplified for N-myc. RESULTS: Among 19 stroma-rich tumors, 11 had grossly visible neuroblastic nodules, and two of these had N-myc amplification. Of 213 stroma-poor tumors, 51 had N-myc amplification, all of which were undifferentiated, and 45 (88% of 51) had high MKI. This histologic phenotype was present in less than 10% of tumors with nonamplified N-myc. Of 162 stroma-poor tumors that showed nonamplified N-myc, 45 (28%) were differentiating and 121 (75%) had low MKI. Neuroblastomas of clinical stages I, II, and IV-S nearly always had favorable histology and no amplification of N-myc. Stage III (regional) and particularly stage IV (metastatic) tumors, however, frequently had unfavorable histologic features with or without N-myc amplification. The estimated PFS at the end of 4 years after diagnosis was 83% for patients whose tumors had favorable histology and no N-myc amplification. The estimated PFS for the patients whose neuroblastomas had unfavorable histology, however, was 29% without and 13% with N-myc amplification, respectively. Subsets of patients with stage II, III, or IV disease were identified by both histologic evaluation and N-myc analysis. Multivariate Cox regression analysis indicated that both the histologic and N-myc-based stratifications provided prognostic information that was independent of staging. CONCLUSIONS: Neuroblastomas with N-myc amplification have a characteristic histopathologic phenotype and an aggressive clinical course. In contrast, neuroblastomas without N-myc amplification exhibit a wide range of histologic features that can define prognostic subsets.

Chi-Square Distribution↗
PubMed1988

Implementation of the group sequential methodology in a randomized trial in metastatic colorectal carcinoma.

A prospective randomized trial using the group sequential statistical method with frequent planned interim analyses was initiated in patients with metastatic colorectal adenocarcinoma comparing methotrexate and 5 fluorouracil (MTX-FU) to methyl CCNU, vincristine, FU, and streptozotocin (MOF-Strep). As a requirement of the group sequential design, a p value of 0.0125 was necessary to stop the trial at the first analysis. The first analysis was done after 17 patients were entered in each study arm and revealed six partial responses to MOF-Strep (35%) and one partial response to MTX-FU (6%) (p = 0.017). As a result, patient accrual continued. Problems encountered with the implementation of the group sequential methodology and the importance of stratification for prognostic variables are discussed.

Adult↗
PubMed2004

Pathologically and biologically distinct types of epithelium in intraductal papillary mucinous neoplasms: delineation of an "intestinal" pathway of carcinogenesis in the pancreas.

Although general characteristics of intraductal papillary mucinous neoplasms (IPMNs) and their delineation from other pancreatic tumors have been well established, several issues regarding their biology and management remain unresolved. It has been noted briefly by us and other authors that there are different types of papillae in IPMNs; however, their frequency, biologic significance, and clinical relevance are unknown. In this study, the association of different papillary patterns with clinical, pathologic, and biologic parameters was studied in 74 IPMNs, and the expression profile of CDX2 (a specific marker and one of the key determinants of intestinal "programming," and a tumor suppressor) was determined immunohistochemically in addition to MUC1 (a marker of an "aggressive" phenotype in pancreatic neoplasia) and MUC2 ("intestinal type mucin," a marker of the "indolent" phenotype, and a tumor suppressor). The patterns of papillae identified and their association with these parameters were as follows: 1) The intestinal-type (Yonezawa's dark-cell type), similar to villous adenomas, was seen in 26 of 74 (35%) cases. The majority harbored carcinoma in situ (85%) or borderline atypia (15%). They tended to be large (mean, 5.5 cm). Most expressed CDX2 (95%) and MUC2 (92%) but not MUC1 (8%). This type was more commonly associated with colloid-type invasion (14 of 16 invasive carcinomas were of colloid type). 2) The pancreatobiliary type, characterized by arborizing papillae lined by cuboidal cells resembling papillary neoplasms of the biliary tract, was present in 22% of the cases. These were mostly graded as carcinoma in situ (94%); they rarely expressed CDX2 (6%) or MUC2 (19%) but often showed MUC1 labeling (44%). This pattern was more commonly associated with the tubular type of invasive carcinoma and had a slight tendency for a more aggressive clinical course. 3) The null type was characterized by abundant apical mucin and basally located nuclei, similar to the gastric foveolar epithelium. Thirty-one percent of IPMNs had this type of papillae, but this pattern was also present in the background of other IPMNs and in the cystic components of most cases as well. Most pure null-type IPMNs were devoid of complexity and consequently classified as adenoma (48%). They tended to be small (mean, 2.6 cm), were often negative for CDX2, MUC1, and MUC2, and were rarely associated with invasive carcinoma. 4) Some IPMNs (12%) exhibited features that were difficult to classify, and 2 cases had a mixture of pancreatobiliary and intestinal types of papillae. In conclusion, IPMNs include pathologically and biologically distinct epithelial patterns. CDX2 and MUC2 expression is relatively specific for the intestinal type papillae, confirming that these IPMNs indeed exhibit intestinal differentiation. Their close association with colloid carcinoma, which also shows consistent MUC2 and CDX2 expression, supports the existence of an intestinal pathway of carcinogenesis. This "metaplastic" pathway may reflect different genetic events in the development of these IPMNs, and the presence of intestinal differentiation may potentially be used in prognostication and stratification of patients into appropriate treatment categories.

Adenocarcinoma, Mucinous↗
PubMed2005

Postoperative surveillance protocol for patients with localized and locally advanced renal cell carcinoma based on a validated prognostic nomogram and risk group stratification system.

PURPOSE: We created an evidence based postoperative surveillance protocol for patients with localized and locally advanced renal cell carcinoma (RCC) based on a risk group stratification system. MATERIALS AND METHODS: 559 patients undergoing surgery for localized and ocally advanced RCC were stratified into low risk (LR), intermediate risk (IR) and high risk (HR) groups based on the University of California-Los Angeles Integrated Staging System (UISS). Tumor recurrences were identified and categorized according to time and location. RESULTS: Patients with localized disease had a lower 5-year recurrence rate than patients with locally advanced (nodal) disease (27.6% vs 64%, p <0.0001). Patients in the LR, IR, and HR groups following nephrectomy demonstrated 5-year recurrence-free rates of 90.4%, 61.8%, and 41.9%, respectively (p <0.0001), and median times to recurrence of 28.9, 17.8 and 9.5 months, respectively (p <0.0001). Chest and abdomen recurrences comprised of 75% and 37.5%, 77.4% and 58.1%, and 45.2% and 67.7% of recurrences in the LR, IR and HR groups, respectively. In patients with node positive disease, chest and abdomen comprised of 58.8% and 76.5% of recurrences, respectively. Patients undergoing partial nephrectomy did not demonstrate a greater rate of local or distant recurrence compared with patients undergoing radical nephrectomy. CONCLUSIONS: Significant differences in incidence and time to recurrence following surgical resection for RCC mandates unique surveillance protocols for patients in each of the UISS risk groups. LR group patients should be followed for at least 5 years, whereas IR and HR group patients require longer surveillance. HR group patients require more stringent abdominal surveillance, whereas LR group patients should emphasize the chest. Patients with nodal disease also require stringent followup. Patients undergoing partial nephrectomy for localized disease can be followed according to the same UISS risk group based protocol.

Adult↗
PubMed1981

Methodological aspects in the design of secondary prevention trials.

The aim of a secondary preventive trial is to produce results that may serve as a basis for therapeutic recommendations to other patients. The natural history of a disease studied including the mortality and reinfarction rate must be known and taken into consideration. The patients should be recruited without selection. By comparing the placebo mortality with expected levels the representativeness of patients can be assessed. One type of treatment can be expected to give different results in different groups of patients with the same disease, thus, prognostic prospective stratification may increase the value of comparisons and conclusions. The registration of end-points should preferably be done by a separate independent organization. Carefully classified specific mortality may be used as a major end-point in addition to total mortality. Similarly, different modes of deaths, e.g. sudden death, may be used if reliable definitions are used. Confounding factors are often difficult to isolate and identify and may have profound effects on the interpretation of a study. In all studies it is mandatory that the patient characteristics on entry do not differ between the different treatment groups. Concomitant treatment should be administered according to standardized criteria. The drop-out rate should be kept at a minimum. The possibility of generalization decreases with increasing drop-out rate. If the follow-up time becomes too long it is likely that at some time the relative benefit becomes less. Since the proportion of non-cardiovascular deaths increases with follow-up and age it may be critical to decide on the relevant follow-up time.

Adult↗
PubMed1996

Prognostic value of noninvasive risk stratification in younger and older patients referred for evaluation of suspected coronary artery disease.

OBJECTIVES: The purpose of this investigation is to explore the relationship of patient gender and age on coronary artery disease diagnostic evaluation and to assess the impact of noninvasive testing results on coronary revascularization rates and cardiac event-free survival. STUDY DESIGN: Retrospective observational cohort. PARTICIPANTS: From a series of 5322 consecutively tested patients from a Midwestern university tertiary medical center, a hospital cohort of 1345 patients with clinically suspected coronary artery disease was enrolled from 1988 through 1989. MEASUREMENTS AND RESULTS: Cardiac risk factor and symptom profiles were worse in women, whereas rates of positive test results were similar in both sexes. Multivariable-adjusted risk for follow-up diagnostic testing was 1.8 and 1.9 times greater, respectively, for men < or = and > 65 years of age than for women (P < .01). Younger women were 4.9 times (P = .001) more likely to experience a cardiac event than younger men, with no differences between younger and older women (relative risk = 1.1; P > .20). Overall cardiac event rates were 2.3, 7.4, 16.7, and 20.2% for young men, young women, older women, and older men, respectively. Initial screening was delayed 2 to 7 times longer for older and younger women compared with men (P < .001); the greatest delays were observed for younger women. Diagnostic follow-up and subsequent cost of total care from initial evaluation through 2 years of follow-up were higher for men than for women (P < .0001), with older women having the lowest rate of subsequent diagnostic and interventional follow-up. In the highest risk patients, subsequent utilization rates were 40 and 20% higher for younger and older men than for similarly aged women. In particular, diabetics were less likely to undergo follow-up diagnostic testing and revascularization (67% younger women). CONCLUSIONS: Age appears to significantly and differently influence decisions regarding noninvasive and invasive medical service utilization in men and women and may partially account for variable outcomes in this and previous gender-based comparisons.

Adult↗
PubMed1998

Can postal prompts from general practitioners improve the uptake of breast screening? A randomised controlled trial in one east London general practice.

OBJECTIVE: To determine the effect on the uptake of breast screening of a personalized letter from the general practitioner recommending mammography, sent to coincide with an invitation from the NHS breast screening programme. DESIGN: Randomised control trial with stratification of prognostic variables. SETTING: A group practice in Hackney, east London. SUBJECTS: 473 women invited for breast screening by the City and East London Breast Screening Service. OUTCOME MEASURE: Attendance for mammography. RESULTS: All women in the randomised trial were followed up; 134 of 236 (57%) randomly allocated to receive the prompting letter attended for mammography compared with 120 of 234 (51%) controls This difference was not significant (chi 2 = 1.43, p = 0.23) CONCLUSION: Personal recommendation by a letter prompting attendance for mammography from the general practitioner known best to women due to be screened did not improve uptake of breast screening in this east London practice. Other strategies are needed to increase uptake of mammography in inner cities.

Family Practice↗
PubMed2004

Outcome prediction in patients at high risk for coronary artery disease: comparison between 99mTc tetrofosmin and 99mTc sestamibi.

PURPOSE: To determine if there was any difference in the ability of physicians to predict prognosis with technetium 99m ((99m)Tc) sestamibi or (99m)Tc tetrofosmin in a large consecutive series of patients at high risk for coronary artery disease who underwent coronary angiography. MATERIALS AND METHODS: This study included 1,818 consecutive patients who underwent a rest and stress single photon emission computed tomographic (SPECT) examination with either (99m)Tc sestamibi (n = 915) or (99m)Tc tetrofosmin (n = 903) and cardiac catheterization. A clinical index was generated and consisted of clinical and demographic variables. Information concerning death, cardiovascular death, and nonfatal myocardial infarction was 93% complete during the 1.5-year study period. Cox proportional hazards models were generated to help determine the incremental contribution of SPECT sum stress score (SSS) and the imaging agent variable to the clinical index. RESULTS: Exercise was used for stress testing in 473 (52%) patients who received (99m)Tc tetrofosmin and 519 (57%) patients who received (99m)Tc sestamibi (P =.06). Cardiovascular death or myocardial infarction occurred in 130 patients. Resulting P values for chi(2) differences between models for the end points of (a) death from any cause, (b) cardiovascular death, and (c) cardiovascular death or myocardial infarction showed that SSS combined with clinical index was a significantly better model than adjusting for only baseline characteristics (P =.001, P <.001, P =.004, respectively). Incremental addition of either (99m)Tc tetrofosmin or (99m)Tc sestamibi to those models containing SSS and the clinical index did not show further significant improvement (P =.87, P =.88, and P =.26 for death from any cause, cardiovascular death, and cardiovascular death or myocardial infarction, respectively). CONCLUSION: This study shows that the type of clinically available (99m)Tc-labeled myocardial perfusion agents should not affect interpretation of results for risk stratification and prognostic assessment.

Adenosine↗
PubMed2005

Targeted inhibition of the KLF6 splice variant, KLF6 SV1, suppresses prostate cancer cell growth and spread.

Prostate cancer is a leading cause of cancer death in men. Risk prognostication, treatment stratification, and the development of rational therapeutic strategies lag because the molecular mechanisms underlying the initiation and progression from primary to metastatic disease are unknown. Multiple lines of evidence now suggest that KLF6 is a key prostate cancer tumor suppressor gene including loss and/or mutation in prostate cancer tumors and cell lines and decreased KLF6 expression levels in recurrent prostate cancer samples. Most recently, we identified a common KLF6 germ line single nucleotide polymorphism that is associated with an increased relative risk of prostate cancer and the increased production of three alternatively spliced, dominant-negative KLF6 isoforms. Here we show that although wild-type KLF6 (wtKLF6) acts as a classic tumor suppressor, the single nucleotide polymorphism-increased splice isoform, KLF6 SV1, displays a markedly opposite effect on cell proliferation, colony formation, and invasion. In addition, whereas wtKLF6 knockdown increases tumor growth in nude mice >2-fold, short interfering RNA-mediated KLF6 SV1 inhibition reduces growth by approximately 50% and decreases the expression of a number of growth- and angiogenesis-related proteins. Together, these findings begin to highlight a dynamic and functional antagonism between wtKLF6 and its splice variant KLF6 SV1 in tumor growth and dissemination.

Alternative Splicing↗
PubMed1993

A randomized controlled trial on the treatment for acute partial ischemic stroke with acupuncture.

The effectiveness of acupuncture in acute stroke remains largely untested and unproved. A randomized, controlled trial was carried out to study the feasibility of acupuncture in combination with conventional supportive treatment for acute stroke patients. A total of 30 patients, aged 46-74, with the onset of symptoms within 36 h were enrolled into the study after appropriate screening. All patients gave informed consent. Basing on the same supportive treatment, patients were randomly assigned to a treatment with or without acupuncture. The procedure and acupoint selection were discussed and decided through several meetings of a group of senior acupuncture doctors in Taiwan. Acupuncture was applied 3 times/week for 4 weeks. During the study period, there were no problems in conducting this trial in terms of patient availability and acceptance, and physician cooperation. A significantly better neurologic outcome was observed in the acupuncture group on day 28 and day 90. The improvement in neurologic status was greatest in patients with a poor neurologic score at baseline. There were no important side effects except for one episode of dizziness related to acupuncture treatment. The data and results of this study will be used as a guideline for planning a full-scale clinical trial, e.g. sample size calculation, method of randomization with stratification of prognostic factors, choosing acupuncture points and technique of acupuncture.

Acupuncture Points↗
PubMed1997

An introduction to the statistical design of phase III cancer clinical trials.

Unless a phase III clinical trial is properly designed, it may be impossible to draw valid conclusions concerning the relative efficacy of the treatments being studied. The purpose of this paper is to present the basic principles of trial design as related to treatment assignment by randomization, the stratification for prognostic factors, the number of treatments to be compared and the determination of the sample size. Emphasis is placed on the distinction between the number of events and the number of patients required in time to event analyses and between trials designed to detect a difference and trials attempting to show treatment equivalence.

Clinical Trials, Phase III as Topic↗
PubMed2006

B-type natriuretic peptide concentrations and myocardial dysfunction in critical illness.

B-type natriuretic peptide (BNP) is the first biomarker of proven value in screening for left ventricular dysfunction. The availability of point-of-care testing has escalated clinical interest and the resultant research is defining a role for BNP in the investigation and treatment of critically ill patients. This review was undertaken with the aim of collecting and assimilating current evidence regarding the use of BNP assay in the evaluation of myocardial dysfunction in critically ill humans. The information is presented in a format based upon organ system and disease category. BNP assay has been studied in a spectrum of clinical conditions ranging from acute dyspnoea to subarachnoid haemorrhage. Its role in diagnosis, assessment of disease severity, risk stratification and prognostic evaluation of cardiac dysfunction appears promising, but requires further elaboration. The heterogeneity of the critically ill population appears to warrant a range of cut-off values. Research addressing progressive changes in BNP concentration is hindered by infrequent assay and appears unlikely to reflect the critically ill patient's rapidly changing haemodynamics. Multi-marker strategies may prove valuable in prognostication and evaluation of therapy in a greater variety of illnesses. Scant data exist regarding the use of BNP assay to alter therapy or outcome. It appears that BNP assay offers complementary information to conventional approaches for the evaluation of cardiac dysfunction. Continued research should augment the validity of BNP assay in the evaluation of myocardial function in patients with life-threatening illness.

Biomarkers↗