Prognostic Value Of Serial Measurements Research Articles

Clinical significance of time-varying on-treatment platelet reactivity after percutaneous coronary intervention

Abstract Objectives This study aimed to determine the prognostic value of serial measurement of platelet reactivity (PR) using the VerifyNow, P2Y12 reaction unit (PRU) assay following percutaneous coronary intervention (PCI) during antiplatelet therapy. Background On-treatment PR changes over time, but the prognostic value of serial PR measurements has not been defined. Methods We enrolled 3204 patients who had PCI and who were measured at PCI and 1 month. We constructed regular and time-dependent Cox proportional hazard models to compare the prognostic value between baseline and serial FU of PR on a primary endpoint of cardiovascular death, myocardial infarction (MI) or stroke over a three-year period. Results Time-varying PR and baseline PR were both associated with an increased risk of the primary endpoint, but the duration of association with primary endpoint differed. The prognostic value of time-varying PR (adjusted hazard ratio (HR) 1.008, 95% confidence interval (CI) 1.005–1.011, p=0.001) was rapidly decreased until 3 month and no prognostic value of time-varying PR after 3 month (adjusted HR 0.999, 95% CI 0.997–1.002, p=0.683). Baseline PR was associated with an increased risk of primary endpoint upto 1 year (adjusted HR 1.005, 95% CI 1.003–1.008, p<0.001) and no prognostic value of baseline PR after 1 year (adjusted HR 0.999, 95% CI 0.997–1.002, p=0.827) was not noted, which showed more slow reduction of the prognostic value of baseline PR. Conclusions Time-varying on-treatment PR reflects more real-world clinical practice. The prognostic value of PR decreased rapidly after PCI and we have to be cautious to use of single time point for the prediction of clinical event using on-treatment PR. Funding Acknowledgement Type of funding sources: None.

Dynamic risk stratification using serial measurements of plasma concentrations of natriuretic peptides in patients with heart failure

BackgroundPrognostic models for patients with chronic heart failure are generally based on a single assessment but treatment is often given with the intention of changing risk; re- evaluation of risk is an important aspect of care. The prognostic value of serial measurements of natriuretic peptides for the assessment of changes in risk is uncertain. AimsTo evaluate the prognostic value of serial measurements of plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP) during follow-up of out-patients with chronic heart failure (CHF). MethodsPatients diagnosed with CHF between 2001 and 2014 at a single out-patient clinic serving a local community were included in this analysis. NT-proBNP was measured at the initial visit and serially during follow-up. Only patients who had one or more measurements of NT-proBNP after baseline, at 4, 12 and/or 24 months were included. ResultsAt baseline, amongst 1998 patients enrolled, the median age was 73 (IQR: 64–79) years, 70% were men, 31% were in NYHA class III/IV, and 77% had NT-proBNP >400 pg/mL. Median follow-up was 4.8 (IQR: 2.5–8.6) years. Serial measurements of NT-proBNP improved prediction of all-cause mortality at 3 years (c- statistic = 0.71) compared with using baseline data only (c-statistic = 0.67; p < 0.001) but a model using only the most recent NT-proBNP had an even higher c-statistic (0.72; p < 0.001). Similar results were obtained based on long-term prediction of mortality using all available follow-up data. ConclusionsSerial measurement of NT-proBNP in patients with CHF improves prediction of all-cause mortality. However, using the most recent value of NT-proBNP has similar predictive power as using serial measurements.

The reproducibility and prognostic value of serial measurements of heart rate response to regadenoson during myocardial perfusion imaging.

The heart rate response (HRR, percentage change from baseline) to regadenoson during myocardial perfusion imaging (MPI) can provide incremental prognostic value in patients with known or suspected coronary artery disease. Our purpose was to evaluate the variability and prognostic value of HRR on serial measurements. We studied 648 consecutive patients (61 ± 11years, 48% with diabetes) who underwent two regadenoson MPI studies (16 ± 9months between studies). HRR <30% was defined as abnormal. All-cause mortality was determined by chart review and verified using the US Social Security Death Master File. HRR was well correlated between the two studies (intraclass correlation coefficient 0.72, 95% CI 0.67 - 0.76) with no systematic bias (mean difference 0.88%, p = 0.2) or proportional bias (p = 0.5) by Bland-Altman analysis in all patients and in those with normal MPI on both studies. Of the 308 patients (48%) with normal baseline HRR (HRR-1), 33% had developed a blunted HRR on the second MPI study (HRR-2). Older age, male gender, end-stage renal disease, and abnormal baseline left ventricular ejection fraction were independent predictors of a new-onset abnormal HRR. During a mean follow-up of 2.4 ± 1.2years, 55 patients (8.5%) died. Patients with a blunted HRR-1 had increased mortality risk irrespective of their HRR-2 (p = 0.9, log-rank test). Among patients with normal HRR-1, a blunted HRR-2 was an independent predictor of all-cause mortality beyond clinical and traditional MPI data (hazard ratio 2.83, 95% CI 1.14 - 7.03). Finally, patients with a normal HRR-1 and HRR-2 had the lowest event rate, while those with any abnormal HRR had an increased risk of death (hazard ratio 2.5, 95% CI 1.2 - 5.4). There was good correlation in the HRR to regadenoson on serial measurements without systematic or proportional biases. Patients with consistently normal HRR had the best prognosis.

Plasma HMGB-1 and Nucleosome Concentrations in Horses with Colic and Healthy Horses.

BackgroundAcute gastrointestinal disease occurs commonly in horses. Novel biomarkers might improve the understanding of SIRS and aid diagnosis and determination of prognosis.HypothesesIncreased plasma concentrations of the biomarkers HMGB‐1 and nucleosomes are associated with severity of gastrointestinal lesions in horses; concentrations of these biomarkers will be greater in horses with lesions more likely to cause SIRS; and will provide additional information compared with standard biomarkers fibrinogen and SAA.AnimalsThirty horses with gastrointestinal disease, 22 healthy horses.MethodsProspective study. Plasma samples taken on admission were used for measurement of HMGB‐1, nucleosomes, fibrinogen, and SAA. Values were compared between healthy horses and those with gastrointestinal disease, and between horses with gastrointestinal disease grouped by lesion type (inflammatory, strangulating, and nonstrangulating). Correlations between biomarkers were assessed.ResultsPlasma concentrations of all biomarkers were significantly higher in horses with gastrointestinal disease compared to healthy horses (P ≤ .001). HMGB‐1 and nucleosomes were significantly higher in inflammatory and strangulating groups compared to healthy horses (3.5‐fold and 5.4‐fold increases, respectively, for HMGB‐1 (P < .05) and 4.8‐fold and 5.6‐fold increases for nucleosomes (P < .05)), but concentrations in the group with nonstrangulating disease did not differ from healthy horses. There was significant correlation between HMGB‐1 and nucleosomes (Spearman's r = 0.623; P < .001), and fibrinogen and SAA (Spearman's r = 0.801; P < .001) but not between other biomarkers.Conclusions and Clinical ImportanceHigh mobility group box‐1 and nucleosomes might have use as biomarkers for horses with gastrointestinal disease. Further studies are required to determine kinetics and prognostic value of serial measurements of these biomarkers in horses.

Prognostic Value of Serial Measurements of Soluble Suppression of Tumorigenicity 2 and Galectin-3 in Ambulatory Patients With Chronic Heart Failure

BackgroundB-Type natriuretic peptides (BNP) and cardiac troponin T (cTnT) predict cardiovascular events in heart failure (HF) patients, but additional refinement in risk stratification may be possible by targeting pathways leading to fibrosis. We aimed to assess the value of serial measurements of soluble suppression of tumorigenicity 2 (sST2) and galectin-3 to identify risk for adverse pathophysiologic processes. MethodsNew York Heart Association (NYHA) functional class III–IV HF patients (n = 180; LVEF ≤40%) were prospectively evaluated with biomarkers collected every 3 months over 2 years and analyzed regarding a primary end point of death/cardiac transplantation and a secondary end point of HF-related hospitalization or death/transplantation. ResultsTime-dependent univariate analyses demonstrated that elevations of sST2 (≥49.3 ng/mL male, ≥33.5 ng/mL female) and galectin-3 (≥22.1 ng/mL) were predictive of the primary and secondary end points. In multivariate models adjusted for BNP, cTnT, and clinical variables, sST2 but not galectin-3 remained an independent predictor (hazard ratio 3.22, 95% confidence interval 1.76–5.89; P < .001). With serial measurements, only sST2 demonstrated incremental value in reclassifying patients to higher risk. ConclusionsSerial monitoring of sST2 (indicating myocardial fibrosis and remodeling) and cTnT (reflecting myocardial injury) identifies highest-risk HF outpatients and may be valuable to guide patient tailored therapy during follow-up evaluations. Serial galectin-3 monitoring in ambulatory HF patients may not be of benefit.

Liver Function, In-Hospital, and Post-Discharge Clinical Outcome in Patients With Acute Heart Failure—Results From the Relaxin for the Treatment of Patients With Acute Heart Failure Study

BackgroundElevated plasma concentrations of liver function tests are prevalent in patients with chronic heart failure (HF). Little is known about liver function in patients with acute HF. We aimed to assess the prevalence and prognostic value of serial measurements of liver function tests in patients admitted with acute decompensated HF. MethodsWe investigated liver function tests from all 234 patients from the Relaxin for the Treatment of Patients With Acute Heart Failure study at baseline and during hospitalization. The end points were worsening HF through day 5, 60-day mortality or rehospitalization, and 180-day mortality. ResultsMean age was 70 ± 10 years, 56% were male, and most patients were in New York Heart Association functional class III/IV (73%). Abnormal liver function tests were frequently found for alanine transaminase (ALT; 12%), aspartate transaminase (AST; 21%), alkaline phosphatase (12%), and total bilirubin (19%), and serum albumin (25%) and total protein (9%) were decreased. In-hospital changes were very small. On a continuous scale, baseline ALT and AST were associated with 180-day mortality (hazard ratios [HRs; per doubling] 1.52 [P = .030] and 1.97 [P = .013], respectively) and worsening HF through day 5 (HRs [per doubling] 1.72 [P = .005] and 1.95 [P = .008], respectively). Albumin was associated with 180-day mortality (HR 0.86; P = .001) but not with worsening HF (HR 0.95; P = .248). Total protein was associated with only worsening HF (HR 0.91; P = .004). ConclusionsAbnormal liver function tests are often present in patients with acute HF and are associated with an increased risk for mortality, rehospitalization, and in-hospital worsening HF.

Prognostic value of procalcitonin, C-reactive protein and leukocytes in septic shock

ObjectivesThis study evaluates the potential prognostic value of serial measurements of different biomarkers (procalcitonin [PCT], C-reactive protein and leukocytes [CRP]) in septic shock patients. DesignProspective observational study. SettingIntensive care unit of a third-level University Hospital. PatientsThe study comprised a total of 88 septic shock patients defined using the 2001 Consensus Conference SCCM/ESICM/ACCP/ATS/SIS criteria. The PCT, CRP and leukocytes were recorded on admission to the ICU and again 72h after admission. InterventionsNone. ResultsThose patients with increasing procalcitonin levels showed higher hospital mortality than those with a decreasing levels (58.8% vs 15.4%, p<0.01). No such effect was observed in relation to C-reactive protein or leukocytes. The best area under the curve for prognosis was for procalcitonin clearance (0.79). A procalcitonin clearance of 70% or higher offered a sensitivity and specificity of 94.7% and 53%, respectively. ConclusionsSerial procalcitonin measurements are more predictive of the prognosis of septic shock patients than single measurements of this parameter. The prognostic reliability of the latter is also better than in the case of C-reactive protein and leukocytes. The application of serial procalcitonin measurements may allow the identification of those septic patients at increased mortality risk, and help improve their treatment.

Prognostic value of serial measurements of highly sensitive cardiac troponin I in stable outpatients with nonischemic chronic heart failure

Prognostic value of serial measurements of highly sensitive cardiac troponin I in stable outpatients with nonischemic chronic heart failure

Valor pronóstico del aclaramiento de procalcitonina, PCR y leucocitos en el shock séptico

ObjetivesThis study evaluates the potential prognostic value of serial measurements of different biomarkers (procalcitonin [PCT], C-reactive protein and leukocytes [CRP]) in septic shock patients. DesignProspective observational study. SettingIntensive care unit of a third-level University Hospital. PatientsThe study comprised a total of 88 septic shock patients defined using the 2001 Consensus Conference SCCM/ESICM/ACCP/ATS/SIS criteria. The PCT, CRP and leukocytes were recorded on admission to the ICU and again 72hours after admission. InterventionsNone. ResultsThose patients with increasing procalcitonin levels showed higher hospital mortality than those with a decreasing levels (58.8% vs. 15.4%, P<0.01). No such effect was observed in relation to C-reactive protein or leukocytes. The best area under the curve for prognosis was for procalcitonin clearance (0.79). A procalcitonin clearance of 70% or higher offered a sensitivity and specificity of 94.7% and 53%, respectively. ConclusionsSerial procalcitonin measurements are more predictive of the prognosis of septic shock patients than single measurements of this parameter. The prognostic reliability of the latter is also better than in the case of C-reactive protein and leukocytes. The application of serial procalcitonin measurements may allow the identification of those septic patients at increased mortality risk, and help improve their treatment.

Prognostic value of serial measurements of highly sensitive cardiac troponin I in stable outpatients with nonischemic chronic heart failure

Cardiac troponin I (cTnI) is a useful biomarker in patients with chronic heart failure (CHF), and a highly sensitive cTnI (hs-cTnI) commercial assay has become available. However, the prognostic role of serial measurements of hs-cTnI in stable outpatients with CHF remains unknown. At entry to the study, we evaluated 95 stable outpatients with nonischemic CHF showing a serum hs-cTnI (Centaur TnI-Ultra [Siemens Medical Solution Diagnostics, New York, NY], lower limit of detection 0.006 ng/mL) value ≥0.006 ng/mL. To evaluate the role of repetitive measurements of hs-cTnI, we performed echocardiography and measured serum levels of cTnI and N-terminal proBNP at baseline and 6 months later and then prospectively followed up these patients for 4.25 years. During long-term follow-up, there were 27 cardiac deaths. On multivariate analyses, high plasma N-terminal pro-brain natriuretic peptide (≥711 pg/mL, P = .0008), high serum hs-cTnI at baseline (≥0.03 ng/mL, P = .0011), and an increase in hs-cTnI (Δhs-cTnI ≥0 ng/mL, P = .022) after 6 months were independent significant prognostic predictors. The hazard ratio for mortality of patients with high hs-cTnI (≥0.03 ng/mL) and an increase in hs-cTnI (Δhs-cTnI ≥0 ng/mL) was 3.59 (95% CI 1.3-9.9, P = .014) compared with that of those with high hs-cTnI (≥0.03 ng/mL) and a decrease in hs-cTnI (Δhs-cTnI <0 ng/mL). These findings indicated that not only the serum concentration of hs-cTnI at baseline but also an increase in hs-cTnI were independent and useful prognostic predictors in patients with nonischemic CHF.

505: Prognostic Value of Serial Measurements of NT-proBNP in Children with Heart Failure

505: Prognostic Value of Serial Measurements of NT-proBNP in Children with Heart Failure

Association of improvement of brachial artery flow-mediated vasodilation with cardiovascular events

The aim of this pilot study was to test the prognostic value of serial measurements of peripheral endothelial function, assessed by brachial artery flow-mediated dilation (FMD), in patients with angiographically proven coronary artery disease. In 68 patients, FMD was measured on the day after coronary angiography and again after a mean of 14 +/- 12 months. Patients were divided into two groups: absolute improvement in FMD > or = 3% (FMD-improver = FMD-i) and < 3% (FMD-non-improver = FMD-ni). After a mean follow-up of 44 +/- 12 months, cardiovascular events were recorded. Baseline characteristics were similar between groups, except the number of risk factors which was smaller in FMD-i (1.6 +/- 0.7 vs 2.1 +/- 0.9, p < 0.02). Cardiovascular events were more frequent in FMD-ni (9 vs 1 event; p < 0.05). In Kaplan-Meier analysis, a trend towards a better outcome in patients with improved FMD was found using the log-rank test (p = 0.08). The single baseline FMD showed no relationship with late cardiovascular events. Thus, 'delta-FMD' may be more closely related to prognosis than a single FMD measurement.

Serum phosphate is an early predictor of outcome in severe acetaminophen-induced hepatotoxicity

Hypophosphatemia is frequently observed in acetaminophen-induced hepatotoxicity and may be involved in the pathogenesis of hepatic failure. The aim of the study was to evaluate the prognostic value of serial measurements of serum phosphate in patients with severe acetaminophen poisoning. Prospectively, serial measurements of serum phosphate were performed in 125 patients with severe acetaminophen poisoning. The optimum threshold value of serum phosphate to discriminate nonsurvivors was identified. Prognostic value and speed of identification were compared with those of the King's College Hospital (KCH) criteria. Phosphate concentrations were significantly higher in nonsurvivors than in survivors at 48 to 72 hours after overdose (mean 2.65 ± 1.18 mmol/L vs. 0.68 ± 0.22 mmol/L, P < .001) as well as 72 to 96 hours after overdose (2.12 ± 0.22 mmol/L vs. 0.59 ± 0.23 mmol/L, P < .001). A threshold phosphate concentration of 1.2 mmol/L at 48 to 96 hours after overdose had sensitivity 89%, specificity 100%, accuracy 98%, positive predictive value 100%, and negative predictive value 98%. The phosphate criteria had higher sensitivity, accuracy, and positive and negative predictive values than the KCH criteria, and it identified patients significantly earlier after transferal [median 1 hour (range 1-38 hours) vs. 12 hours (2-192 hours), P < .05, respectively]. In nonsurvivors, the degree of hyperphosphatemia correlated with renal dysfunction ( R = .55; P = .02). In conclusion, hyperphosphatemia after acetaminophen overdose is seen exclusively in nonsurvivors, which makes it a highly specific as well as sensitive predictor of nonsurvival. We propose that hyperphosphatemia is caused by renal dysfunction in the absence of hepatic regeneration, as the latter appears to be associated with lowering of serum phosphate. (H EPATOLOGY 2002;36:659-665.)

The prognostic value of serial measurements of serum albumin concentration in patients admitted to an intensive care unit

The prognostic value of serial measurements of serum albumin concentration in patients admitted to an intensive care unit

The prognostic value of serial measurements of serum albumin concentration in patients admitted to an intensive care unit.

The prognostic value of serial measurements of serum albumin concentration during the first 72 h after admission to a general adult intensive care unit was retrospectively reviewed in 348 consecutive critically ill patients over a one year period. The accuracy of the admission APACHE II (Acute Physiology And Chronic Health Evaluation) score in correctly predicting patient outcome was compared with the serum albumin concentration measured at different times after intensive care unit admission. Multiple logistical regression analyses were performed to evaluate whether combining APACHE II and serum albumin into a unified risk index improved prognostic accuracy. Serum albumin concentration on admission was lower in non-survivors than in survivors and decreased more rapidly in non-survivors (p < 0.001). The admission serum albumin concentration was found to be an insensitive prognostic indicator. However, serum albumin measured after 24 h was as accurate as the admission APACHE II score in correctly classifying patients according to outcome. There was a good correlation between the admission APACHE II score and serum albumin measured after 24 h but not between the admission APACHE II and the admission serum albumin. Combining the APACHE II score and serial albumin concentrations into a unified risk of death equation did not improve the accuracy of outcome prediction.

Prognostic value of serial determinations of circulating immune complex levels in malignant melanoma.

A total of 50 melanoma patients free of distant metastatic disease and 54 healthy controls were analyzed for circulating immune complexes (cIC) and complement split product (C3d), using solid-phase Clq-anti-IgG radioimmunoassay (RIA), Clq-protein A RIA, and anti-C3d anti-IgG RIA for cIC detection. No significant differences in cIC and C3d levels could be demonstrated between the controls and the 31 patients with primary malignant melanoma analyzed before surgery. To evaluate the prognostic value of serial measurements, samples from the 50 patients were taken at regular intervals for 4 to 27 months (median, 20 months). Surgery was the only treatment given. Significant changes in the cIC and C3d levels were defined by reference to the changes that occurred in 23 of the 54 healthy controls observed for a period of 6 to 55 months (median, 23 months). During the period of serial sampling, recurrent disease developed in 8 of the patients. In only 3 of these 8 patients (versus 10 of 42 patients without recurrence) did significant changes occur, and the changes occurred either at the same time or after the clinical diagnosis of recurrence. During the entire clinical observation period of 6 years, a total of 11 patients developed recurrences. Significant changes were only observed in 4 of these 11 patients versus 8 of 37 patients without recurrence. In conclusion, changes in cIC and/or C3d levels were not found to be indicative of early or long-term recurrence of malignant melanoma.

Prognostic value of serial measurements of leukocyte thymidine uptake in well-controlled chronic myelocytic leukemia

Twenty-nine patients with well-controlled Ph 1-positive CML were followed with peripheral blood and bone marrow thymidine uptake determinations ( 3H-TdR) at approx. six-month intervals over periods of eight to 48 months (median 30 months). Median peripheral blood 3H-TdR of individual patients varied considerably, ranging from 0.6 to 18 dpm/10 3 WBC. However, increases in sequential studies of individual patients were usually less than two-fold. More than four-fold increases (4.1-16-fold, median 7.5-fold) in blood 3H-TdR were recorded in 11 patients. At the time of 3H-TdR increase, there was no or minimal evidence of clinical or hematologic deterioration; chromosome analysis showed new abnormalities in four out of 10 patients. Ten of these 11 patients exhibited criteria of the terminal phase of CML two to six months after the increase in 3H-TdR; the eleventh died of another cause at five months. In contrast, only two of 18 patients without such change in 3H-TdR entered the terminal stage at five and six months and three at seven to 12 months ( p < 0.002). The bone marrow 3H-TdR did not provide significant prognostic information in these patients. Periodic measurement of thymidine uptake by circulating leukocytes may be useful in the follow-up of patients with well-controlled CML, to provide early warning of disease progression.