High Risk For Subsequent Events Research Articles

Comparison of Machine Learning Algorithms for Predicting Hospital Readmissions and Worsening Heart Failure Events in Patients With Heart Failure With Reduced Ejection Fraction: Modeling Study.

Heart failure (HF) is highly prevalent in the United States. Approximately one-third to one-half of HF cases are categorized as HF with reduced ejection fraction (HFrEF). Patients with HFrEF are at risk of worsening HF, have a high risk of adverse outcomes, and experience higher health care use and costs. Therefore, it is crucial to identify patients with HFrEF who are at high risk of subsequent events after HF hospitalization. Machine learning (ML) has been used to predict HF-related outcomes. The objective of this study was to compare different ML prediction models and feature construction methods to predict 30-, 90-, and 365-day hospital readmissions and worsening HF events (WHFEs). We used the Veradigm PINNACLE outpatient registry linked to Symphony Health's Integrated Dataverse data from July 1, 2013, to September 30, 2017. Adults with a confirmed diagnosis of HFrEF and HF-related hospitalization were included. WHFEs were defined as HF-related hospitalizations or outpatient intravenous diuretic use within 1 year of the first HF hospitalization. We used different approaches to construct ML features from clinical codes, including frequencies of clinical classification software (CCS) categories, Bidirectional Encoder Representations From Transformers (BERT) trained with CCS sequences (BERT + CCS), BERT trained on raw clinical codes (BERT + raw), and prespecified features based on clinical knowledge. A multilayer perceptron neural network, extreme gradient boosting (XGBoost), random forest, and logistic regression prediction models were applied and compared. A total of 30,687 adult patients with HFrEF were included in the analysis; 11.41% (3184/27,917) of adults experienced a hospital readmission within 30 days of their first HF hospitalization, and nearly half (9231/21,562, 42.81%) of the patients experienced at least 1 WHFE within 1 year after HF hospitalization. The prediction models and feature combinations with the best area under the receiver operating characteristic curve (AUC) for each outcome were XGBoost with CCS frequency (AUC=0.595) for 30-day readmission, random forest with CCS frequency (AUC=0.630) for 90-day readmission, XGBoost with CCS frequency (AUC=0.649) for 365-day readmission, and XGBoost with CCS frequency (AUC=0.640) for WHFEs. Our ML models could discriminate between readmission and WHFE among patients with HFrEF. Our model performance was mediocre, especially for the 30-day readmission events, most likely owing to limitations of the data, including an imbalance between positive and negative cases and high missing rates of many clinical variables and outcome definitions. We predicted readmissions and WHFEs after HF hospitalizations in patients with HFrEF. Features identified by data-driven approaches may be comparable with those identified by clinical domain knowledge. Future work may be warranted to validate and improve the models using more longitudinal electronic health records that are complete, are comprehensive, and have a longer follow-up time.

Sequential cardiovascular magnetic resonance assessment of left ventricular ejection fraction for prediction of subsequent events in a large multicenter STEMI registry

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” Background. Cardiovascular magnetic resonance (CMR) is the best tool for left ventricular ejection fraction (LVEF) quantification, but as yet the prognostic value of sequential LVEF assessment for major adverse cardiac event (MACE) prediction after ST-segment elevation myocardial infarction (STEMI) is uncertain. Purpose. We explored the prognostic impact of sequential assessment of CMR-derived LVEF after STEMI to predict subsequent MACE. Methods. We recruited 1036 STEMI patients in a large multicenter registry. LVEF (reduced [r]: <40%; mid-range [mr]: 40-49%; preserved [p]: ≥50%) was sequentially quantified by CMR at 1 week and after >3 months of follow-up. MACE was regarded as cardiovascular death or re-admission for acute heart failure after follow-up CMR. Results. During a 5.7-year mean follow-up, 82 MACE (8%) were registered. The MACE rate was higher only in patients with LVEF < 40% at follow-up CMR (r-LVEF 22%, mr-LVEF 7%, p-LVEF 6%; p-value < 0.001). Based on LVEF dynamics from 1-week to follow-up CMR, incidence of MACE was 5% for sustained LVEF³40% (n = 783), 13% for improved LVEF (from <40 to ³40%, n = 96), 21% for worsened LVEF (from ³40% to <40%, n = 34) and 22% for sustained LVEF <40% (n = 100), p-value < 0.001. Using a Markov approach that considered all studies performed, transitions towards improved LVEF predominated and only r-LVEF (at any time assessed) was significantly related to higher incidence of subsequent MACE. Conclusions. LVEF constitutes a pivotal CMR index for simple and dynamic post-STEMI risk stratification. Detection of reduced LVEF (<40%) by CMR at any time during follow-up identifies a small subset of patients at high risk of subsequent events.

Magnetic Resonance Assessment of Left Ventricular Ejection Fraction at Any Time Post-Infarction for Prediction of Subsequent Events in a Large Multicenter STEMI Registry.

Magnetic resonance imaging (MRI) is the most accurate imaging technique for left ventricular ejection fraction (LVEF) quantification, but as yet the prognostic value of LVEF assessment at any time after ST-segment elevation myocardial infarction (STEMI) for subsequent major adverse cardiac event (MACE) prediction is uncertain. To explore the prognostic impact of MRI-derived LVEF at any time post-STEMI to predict subsequent MACE (cardiovascular death or re-admission for acute heart failure). Prospective. One thousand thirteen STEMI patients were included in a multicenter registry. 1.5-T. Balanced steady-state free precession (cine imaging) and segmented inversion recovery steady-state free precession (late gadolinium enhancement) sequences. Post-infarction MRI-derived LVEF (reduced [r]: <40%; mid-range [mr]: 40%-49%; preserved [p]: ≥50%) was sequentially quantified at 1 week and after >3 months of follow-up. Multi-state Markov model to determine the prognostic value of each LVEF state (r-, mr- or p-) at any time point assessed to predict subsequent MACE. A P-value <0.05 was considered to be statistically significant. During a 6.2-year median follow-up, 105 MACE (10%) were registered. Transitions toward improved LVEF predominated and only r-LVEF (at any time assessed) was significantly related to a higher incidence of subsequent MACE. The observed transitions from r-LVEF, mr-LVEF, and p-LVEF states to MACE were: 15.3%, 6%, and 6.7%, respectively. Regarding the adjusted transition intensity ratios, patients in r-LVEF state were 4.52-fold more likely than those in mr-LVEF state and 5.01-fold more likely than those in p-LVEF state to move to MACE state. Nevertheless, no significant differences were found in transitions from mr-LVEF and p-LVEF states to MACE state (P-value=0.6). LVEF is an important MRI index for simple and dynamic post-STEMI risk stratification. Detection of r-LVEF by MRI at any time during follow-up identifies a subset of patients at high risk of subsequent events. 2 TECHNICAL EFFICACY STAGE: 2.

Spironolactone dose in heart failure with preserved ejection fraction: findings from TOPCAT

Spironolactone up-titration may be limited by side effects that could be minimized at lower than target doses, but whether lower than target doses remain efficacious is unknown. In TOPCAT, spironolactone (or placebo) were started at 15 mg/day, and increased up to a maximum of 45 mg/day. The prognostic implications related to spironolactone dose are yet to be reported. We aimed to assess the average spironolactone/placebo doses provided during the trial, overall and within high-risk subgroups (e.g. elderly, renal dysfunction, high potassium); discontinuation rates; and the efficacy of lower than target doses in heart failure with preserved ejection fraction. Overall, 1767 patients from 'TOPCAT-Americas' were included. Linear, logistic and Cox regressions were applied. Patients randomized to spironolactone received lower doses than placebo: 22.5 (15.0-27.5)mg/day vs. 27.5 (17.5-27.5)mg/day (P < 0.001). Patients aged ≥75 years, with an estimated glomerular filtration rate ≤60 mL/min/1.73 m2 , and with potassium levels >4.5 mmol/L, received lower spironolactone doses (median ≈ 20 mg/day). This pattern of dose differences was not observed in patients taking placebo, where the between-subgroup placebo doses were similar (spironolactone-placebo by subgroup Pinteraction < 0.05). Among patients taking spironolactone, 25.4% discontinued the drug during the first year, compared with 18.3% of the patients taking placebo (P < 0.001). Discontinuation rates in the aforementioned high-risk subgroups reached 30% during the first year. Spironolactone reduced the primary outcome of heart failure hospitalization/cardiovascular death without significant heterogeneity between the study subgroups (Pinteraction > 0.1). Spironolactone discontinuation was associated with a two to fourfold higher risk of subsequent events. Spironolactone (but not placebo) was used at lower doses among the elderly, those with renal dysfunction and with higher potassium levels. The effect of spironolactone was homogeneous across these subgroups. In patients unable to tolerate target doses, a low-dose strategy should be preferred to stopping treatment.

Lipid treatment and goal attainment characteristics among persons with atherosclerotic cardiovascular disease in the United States

ObjectiveNational estimates of atherosclerotic cardiovascular disease (ASCVD) in the United States (US) are scarce, especially for patients grouped by cardiovascular risk, lipid-lowering therapy use, and low-density lipoprotein cholesterol (LDL-C) levels. The objective of this study was to estimate the size of the ASCVD population, including the subgroup at very high risk for recurrent events as defined by the 2018 Multi-Society Cholesterol Guidelines. MethodsPatient-level data from the Truven MarketScan Research Database were used and extrapolated to approximate national figures based on known national demographic and ASCVD prevalence numbers. Demographic and clinical characteristics, including LDL-C levels and lipid-lowering therapy use, were captured. ResultsThe extrapolated prevalence of ASCVD in 2014 was 18.3 million, of whom 690,524 had an acute coronary syndrome event in the past year. An estimated 41.4% of patients with ASCVD had diabetes, 44.9% had polyvascular disease, and 23.8% had multiple cardiovascular events. A third of those with ASCVD were estimated to be at very high risk for subsequent events per the 2018 Multi-Society Cholesterol Guidelines. Of those with ASCVD, 74.2% were estimated to have an LDL-C level of ≥70 ​md/dL, and more than half of these patients were neither on statins nor ezetimibe. Only 9.2% of patients with ASCVD and LDL-C ≥70 ​mg/dL were on a high-intensity statin. ConclusionsThe underutilization of lipid-lowering therapies in general, and in particular the relatively low usage of high-intensity statins among patients with uncontrolled LDL-C (including those at very high risk), suggests that eligible patients for proprotein convertase subtilisin/kexin type 9 inhibitor therapy may not be as numerous as previously estimated.

Abstract P366: Pooled Cohort Equation Performance in Primary and Secondary Prevention Subgroups of the SystolicBlood Pressure Intervention Trial (SPRINT)

Background: The Pooled Cohort Equation (PCE) estimates 10-y atherosclerotic cardiovascular disease (ASCVD) risk among adults aged 40-79 years without CVD. Recent studies applied the PCE to mixed primary (1°) and secondary (2°) prevention populations to predict risk of future CVD events. However, the PCE is not validated in 2° prevention populations. We studied the impact of prior CVD on PCE performance in a 2° prevention population of the SPRINT trial. Methods: SPRINT randomized 9,361 adults with hypertension and ≥1 CVD risk factor or prior ASCVD to standard or intensive BP control. Excluding those age &gt;79 years (n=1,158) or missing PCE covariates (n=52), we calculated 10-year ASCVD risk at baseline using the PCE. We assessed PCE discrimination with the C-statistic among all SPRINT participants and among 1° and 2° prevention subgroups. We estimated the hazard ratio (HR) for incident ASCVD events comparing the 2° to the 1° prevention group, controlling for baseline PCE-predicted 10-y risk. Results: Of the 8,151 included participants, 6,874 (84%) and 1,277 (16%) were in the 1° and 2° prevention groups, respectively. Mean (SD) age was 66 (8) years, 35% were female, 34% were black. Median (IQR) baseline predicted 10-year ASCVD risk in the 1° prevention group was lower than the 2° prevention group (P&lt;0.001; Table ). In the 3.3 years of follow-up, ASCVD events occurred more frequently in the 2° prevention group than the 1° prevention group (P&lt;0.001). The C-statistic was 0.618 (95% CI 0.589, 0.646) in the entire analytic population, and was non-significantly higher among the 1° prevention subgroup. Comparing the 2° to 1° prevention population, HR for incident ASCVD events was 2.6 (95% CI 2.1, 3.3) when controlling for baseline PCE-estimated 10-y risk. Conclusions: Adults with prior ASCVD events have a nearly 3-fold higher risk of subsequent events. This study demonstrates that the PCE underestimates risk of recurrent events in 2° prevention populations and use in mixed populations should be avoided.

Pacemaker and Defibrillation Implantation in Patients with Transposition of the Great Arteries

Transposition of the great arteries (TGA) is represented in 5% to 7% of patients with congenital heart disease. These patients face a significant burden of arrhythmia and sudden cardiac death throughout their lives, and many eventually undergo pacemaker or cardiac-defibrillator implantation. Outcomes data following device implantation in this population, however, are limited. From an electrophysiologic database at a large, tertiary care medical center, we identified 63 TGA patients (34 with dextro (d)-TGA and 29 with levo (l)-TGA) with systemic right ventricles receiving an implantable cardiac device from 1996 to 2014. Medical records were reviewed for demographic, echocardiography and device interrogation data. Overall, l-TGA patients were older than d-TGA patients when they underwent initial device implantation (35.6 ± 18.2 versus 17.3 ± 10.6 years, p<0.001), and had more concomitant cardiac defects (55% versus 12%, p<0.001). Survival following initial device implantation was similar between l-TGA and d-TGA (72% versus 74%, p = 1.00), despite the baseline difference in age. Twenty-four patients underwent implantable cardioverter-defibrillator (ICD) implantation: 18 for primary intervention (11 l-TGA and seven d-TGA), and six for secondary prevention (four l-TGA and two d-TGA). Sixty-seven percent of patients in the secondary prevention group had appropriate shocks, compared with 0% of primary prevention patients. Patients with ICD discharge were more likely to have concomitant heart defects (100% versus 30%, p = 0.011). Despite being significantly younger, d-TGA patients had similar survival rates following device implant to l-TGA patients. Patients with TGA and sustained ventricular arrhythmias are at high risk for subsequent events, and typically benefit from ICD implantation. The role of prophylactic ICD implantation in this population, however, remains uncertain.

Abstract 14217: Subsequent Sustained Ventricular Arrhythmia in Patients With Transposition of the Great Arteries Undergoing Device Implantation

Introduction: Current guidelines recommend prophylactic implantable cardioverter-defibrillator (ICD) for patients with an ejection fraction &lt;35%. Whether this applies to patients with transposition of the great arteries (TGA) and ≥moderately depressed systemic ventricular dysfunction is uncertain. Methods: From an electrophysiologic database at a large, tertiary care medical center, we identified 71 patients with TGA (40 D-TGA and 31 L-TGA) receiving an implantable cardiac device from 1996-2014. Electronic and paper medical records were fully reviewed and device interrogation data was collected to assess the frequency of sustained ventricular arrhythmia. Results: Patients were 31±15 years of age, 32% were women, 53% had ≥moderate systemic ventricular dysfunction and 38% had ≥moderate systemic atrioventricular valve regurgitation. Sixteen (23%) had an ICD placed initially. Of the 55 with a pacemaker as their first device 9 were later upgraded to an ICD for primary prevention of sudden death and 1 patient had sustained arrhythmia and an ICD was placed afterwards. Thus, of the 26 patients who eventually underwent ICD implant, 20 received it for primary prevention and 6 for secondary prevention. Interrogation follow-up data spanned 214 patient-years for primary prevention and 41 patient-years for secondary prevention. Only 2 patients received ICD discharges in the primary prevention group and both were inappropriate. In the secondary prevention group, 67% of patients underwent appropriate ICD discharge (0.39 shocks per patient-year, p&lt;0.001 compared to primary prevention). Patients with ICD discharge were older (49±5 vs. 30±15 years, p=0.011) and more likely to have concomitant heart defects (100% vs. 30%, p=0.011). Conclusion: Patients with TGA and sustained ventricular arrhythmia are at high risk for subsequent events and benefit from ICD implantation. The role of prophylactic ICD implant in this patient population, however, remains uncertain.

Abstract 17286: Reconciling Systolic and Diastolic Measures of Left Ventricular Noncompaction Cardiomyopathy in Cardiac Magnetic Resonance

Background: Previously, it was demonstrated that systolic measures identify higher levels of risk for events related to left ventricular noncompaction cardiomyopathy (LVNC) than diastolic measures. This analysis seeks to improve the ability of the diastolic measures to identify LVNC and predict associated events. Methods: Trabeculation/possible LVNC by cMRI was retrospectively observed among 122 consecutive cases. We assessed the extent of trabeculation, end-systolic noncompacted-to-compacted ratios (ESNCCR), end-diastolic noncompacted-to-compacted ratios (EDNCCR) along with myocardial thickening (MT) and ejection fraction (EF). Deaths, CHF readmissions, ventricular arrhythmias, and embolic events were pooled to increase statistical power and used to identify potential LVNC-associated events. Using logistic regression with an ESNCCR ≥ 2 to identify LVNC as the dependent variable and EDNCCR as the independent variable, analysis were performed with receiver operating curves with and without myocardial thickening as a covariate. Next, using pooled LVNC-associated events as the dependent variable, separate models were performed for ESNCCR ≥ 2 and EDNCCR ≥ 2.3, both adjusting for age, race, gender, body surface area, left ventricular ejection fraction, number of trabeculated segments, and myocardial thickening. Results: The area under the curve (AUC) for EDNCCR to identify potential LVNC was 0.84, but with adjustment for myocardial thickening, the AUC was 0.98, which was significantly increased (p-value = 0.005). Without adjusting for myocardial thickening, ESNCCR ≥ 2 was associated with LVNC-associated events, but EDNCCR ≥ 2.3 was not (p-value: 0.003 vs 0.2, respectively). With adjustment for myocardial thickening, both ESNCCR ≥ 2 and EDNCCR ≥ 2.3 were associated with LVNC-associated events (p-value: 0.03 vs 0.03, respectively). Conclusion: In using the diastolic measure to assess for possible left ventricular noncompaction cardiomyopathy, impaired function of the underlying compacted layer is important in identifying those with a higher risk of subsequent events. Further studies are needed to determine if individuals with increased trabeculations with preserved myocardial thickening are at increased risk of future events.

Breast cancer subtypes and outcome after local and regional relapse

To evaluate the outcome of breast cancer patients after locoregional recurrence (LRR) according to tumor biological features evaluated at first diagnosis and at the time of recurrence. We collected information on all consecutive breast cancer patients operated at the European Institute of Oncology between 1994 and 2005. The tumor characteristics and subsequent outcome of patients who experienced LRR were analyzed. Two hundred and seventy nine patients with LRR were identified, 197 and 82 patients with local and regional recurrence respectively. The overall discordance rate between primary cancer and LRR was 9% for estrogen receptor expression, 22% for progesterone receptor and 4% for human epidermal growth factor receptor 2. For patients with regional recurrence, the risk of distant metastasis was significantly higher compared with local relapse in case of late recurrence (hazard ratio [HR] = 2.76; 95% CI 1.31-5.85). Patients with triple-negative breast cancer at LRR experienced a higher risk of subsequent relapse (HR 2.87 [1.67-4.91]) and death (HR 2.00 [1.25-3.19]). LRR correlates with a high risk of subsequent events and death in particular in patients with triple-negative subtype.

Development and Validation of Risk Adjustment Models for Long-Term Mortality and Myocardial Infarction Following Percutaneous Coronary Interventions

Existing models for outcome after percutaneous coronary interventions (PCIs) lack assessment of long-term prognosis. Our goal was to derive 1- and 5-year mortality and mortality/myocardial infarction (MI) risk models for PCI outcomes from simple, easily obtainable clinical and laboratory variables. Using the Mayo Clinic registry, we analyzed long-term mortality and mortality/MI following PCIs on 9165 unique patients from January 1, 2001, through December 31, 2007. Cox proportional hazards regression was used to model the calculated risk score and major procedural complications. A total of 1243 patients died, and 696 had MI. Separate risk models derived from clinical, procedural, and laboratory characteristics were made for mortality and mortality/MI. Older age, comorbid conditions, low ejection fraction, acute MI, history of smoking, heart failure, hyperlipidemia, 3-vessel disease, procedural failure, ventricular arrhythmia during PCI, and low medication score were predictors of long-term mortality and mortality/MI. Simple integer scores stratified patients into low, moderate, high, and very high risk for subsequent events. Models had adequate goodness of fit, and areas under the receiver operating characteristic curve were 0.786 and 0.728 for mortality and mortality/MI, respectively, indicating good overall discrimination. Bootstrap analysis indicated that the model was not overfit to the available data set. Easily obtainable variables can be combined into a convenient risk scoring system at the time of patient dismissal following PCI to accurately predict long-term mortality and mortality/MI. This model may be useful for providing patients with individualized, evidence-based estimates of long-term risk.

Cerebrovascular Disease and its Relationship to Other Vascular Beds: A Comprehensive Review of the Literature

Atherothrombosis, ischaemic heart disease (IHD), cerebrovascular disease (CVD) and peripheral arterial dis- ease (PAD) are a major cause of mortality and are predicted to be the leading cause of death world-wide by 2020. It is now recognised that CVD is part of a family of atherothrombotic diseases such as PAD and IHD. However, despite receiving contemporary evidence-based preventative drug therapy, patients with established arterial disease and those with multiple risk factors for atherothrombosis both experience high cardiovascular (CV) event rates with a 4.7% yearly rate of hard events. People with symptomatic atherosclerosis in 1 vascular bed are at a higher risk of subsequent events in other beds, e.g. patients who suffer a stroke are at a high risk of going on to suffer a coronary event, with a 10 year CV event risk of 42.8%. These findings support the need for increased awareness among physicians and patients for the amount of vascular cross-risk that is related to the overlap between the various beds of atherothrombosis. Atherothrombosis in stroke patients should be considered as a global arterial disease. We present a systematic review of the literature relating to the risk of non-cerebral (especially sub-clinical) atherothrombotic events in ischaemic stroke pa- tients.

Annual Rates of Arterial Thromboembolic Events in Medicare Neovascular Age-Related Macular Degeneration Patients

Smoking, age, and nutrition have been associated with the development of neovascular age-related macular degeneration (AMD) and can increase the risk of arterial thromboembolic events (ATEs). This study assesses annual rates of ATEs in new-onset neovascular AMD patients compared with matched controls. Retrospective study. New-onset neovascular AMD patients and age-, race-, gender-, and database length-matched controls from the 5% Medicare database. We conducted a retrospective analysis of the 5% Medicare database from 2001 to 2003. New-onset neovascular AMD patients were included if they were > or =65 years old, had 2 diagnoses of neovascular AMD, and had at least 1 year of data before the first diagnosis of AMD within the dataset. A control group was constructed in a 3:1 ratio from those without a diagnosis of a major eye disorder and matched by age, race, gender, and length of data. Annual prevalence rates were determined for myocardial infarctions (MIs) and ischemic cerebral vascular accidents (CVAs). Rates of MIs and ischemic CVAs in new-onset neovascular AMD patients and matched controls from 2001 to 2003. There were 15771 new-onset neovascular AMD patients identified and matched with 46 408 controls. Average age was 80.5 years, with 64% > or =80; 65% were female; and 95.9% were white. Inpatient MI rates for neovascular AMD patients and controls were 2.2% and 2.2%, respectively (P = 0.74). Inpatient ischemic CVA rates for neovascular AMD patients and controls were 3.5% and 3.6%, respectively (P = 0.59). Myocardial infarction rates and ischemic CVA rates for both groups increased with age. Subgroups of patients with comorbidities known to be risk factors for ATEs (i.e., hypertension, hyperlipidemia, diabetes, and arrhythmias) had a higher rate of events. Patients with previous ATEs were also at a higher risk of subsequent events, at 7.4% for inpatient MI and 35.1% for inpatient ischemic stroke. Despite the shared risk factors associated with neovascular AMD and ATEs, Medicare beneficiaries with neovascular AMD had a rate of ATEs similar to that of matched controls. Rates of ATEs increased in patients with comorbidities and for patients with previous events.

Final Results of a Placebo-Controlled Study of Filgrastim in Small-Cell Lung Cancer: Exploration of Risk Factors for Febrile Neutropenia

BackgroundA phase III study of filgrastim as an adjunct to combination chemotherapy in previously untreated patients with limited- or extensive-stage small-cell lung cancer was conducted. This final analysis explores baseline factors that might predict febrile neutropenia and also reports the results of 463 open-label filgrastim cycles that were delivered after patients' initial episode of the primary endpoint, ie, febrile neutropenia. Patients and MethodsA total of 244 patients were randomized to receive placebo or filgrastim in ≤ 6 cycles of chemotherapy (cyclophosphamide/doxorubicin/etoposide). ResultsThe cumulative percent of patients receiving filgrastim who experienced febrile neutropenia was approximately 50% lower than those given placebo (38% vs. 74%, respectively; P < 0.0001). Significant treatment-related reductions were also seen in the incidence and duration of grade 4 neutropenia. Cycle 1 displayed the highest incidence of neutropenia with or without fever and the longest duration of neutropenia relative to later cycles. Patients crossing over to open-label filgrastim from their blinded treatment assignment displayed event rates similar to those in the blinded filgrastim group. Patients who experienced febrile neutropenia in cycle 1 were at a significantly higher risk for subsequent events compared with those who were event-free in cycle 1. Women displayed a higher risk for febrile neutropenia than men, but no other baseline risk factors were detected. ConclusionGiven the high rate of febrile neutropenia in cycle 1 and the higher risk for subsequent events in patients with a cycle 1 event, we conclude that growth factor administration starting in cycle 1 should be considered for patients receiving moderately to highly myelosuppressive chemotherapy regimens.

534 The Norris coronary prognostic index predicts increased post-infarction myocardial apoptosis at post-mortem examination in humans

11±3 ml/k/min, p 120 mg%, respectively (p=0.015), 95% vs. 75% in the patents with RAP 8 mHg (p=0.002), 93% vs. 73% in those with peak exercise SBP > and 37, respectively (p=0.001). The 2and 3-years survival rates were, respectively, of only 59% and 47% in the patients with a RAP > 8 mHg and a peak exSBP 8 mHg and a VE/VCO2slope > 37. In conclusion, simple hemodynamic parameters, which may be assessed also noninvasively, and the ventilatory response to ex may identify subgroups of patients with chronic HF at high risk of subsequent events despite long-term BB therapy.

Angiographic changes in saphenous vein grafts are predictors of clinical outcomes

Background Previous studies have suggested that angiographic evidence of disease progression in coronary arteries increases the risk of subsequent coronary clinical events. This study ascertained whether patients enrolled in the Post Coronary Artery Bypass Graft Clinical Trial (POST CABG) who had substantial progression of atherosclerosis in ≥1 saphenous vein grafts (on the basis of assessment of baseline and follow-up angiograms obtained 4-5 years after study entry), but who had not reported clinical symptoms before follow-up angiography, were at a higher risk of subsequent events than patients who did not have substantial progression of atherosclerosis (decrease ≥0.6 mm in lumen diameter at site of greatest change from baseline). Methods All 1351 patients enrolled in the trial underwent baseline angiography; only the 961 patients who had follow-up angiography and no coronary events before the follow-up study were included in this analysis. The clinical center staff contacted patients to ascertain the events that had occurred after follow-up angiography (approximately 3.4 years later). Results Sixty-nine patients had died; 870 patients or relatives were interviewed, and 22 patients could not be contacted. Univariable estimates of relative risk associated with substantial progression ranged from 2.2 (P <.001) for cardiovascular death or nonfatal myocardial infarction to 3.3 (P <.001) for revascularization. Multivariable and univariable estimates of risk were similar. Conclusions The findings provide evidence that patients who had substantial progression of atherosclerosis in vein grafts are at an increased risk for subsequent coronary events and suggest that angiographic changes in vein grafts are appropriate surrogate measures for clinical outcomes. (Am Heart J 2003;145:262-9.)

Long-term results of coronary artery bypass surgery for unstable angina: incidence of mortality, myocardial infarction, and angina resumption.

AbstractTo determine if routine treadmill testing would be helpful in identifying patients at high risk for subsequent events, the first 81 patients to undergo coronary artery bypass0 surgery for unstable angina pectoris at Stanford University Medical Center were reevaluated at four intervals after surgery. Evaluations, including assessment of angina pectoris and a treadmill test, were done at mean times of 18,40, and 72 months after surgery. At a mean time of 90 months postoperatively, angina status was determined in survivors. The prevalence of angina rose from 19% during the first year to 53% during the fourth and fifth postoperative years. Cardiac deaths and myocardial infarctions were frequent during the first postoperative year, and were more frequent in patients with three‐vessel disease and those with one or more severely narrowed coronary arteries which were not bypassed. Cardiac events were rare between 12 and 36 months after operation; clinical and treadmill variables did not predict these events. During the fourth and subsequent postoperative years, the incidence of cardiac events increased. While the presence of stable angina pectoris was the clinical variable most useful prognostically, treadmill testing added additional independent prognostic information (p&lt;0.0001). During the intervals between visits 1 and 2, and visits 2 and 3, cardiac events were ten times more frequent in persons with a maximal heart rate of 130 beats/min or less on the treadmill at 18 and 40 months.We conclude that the prevalence of angina increased steadily during the first 5 postoperative years. Myocardial infarction and cardiac death rates were high during the first postoperative year, low during the second and third postoperative years, and then began to rise thereafter. The early events were more frequent in persons with three‐vessel disease and one or more severely narrowed coronary arteries which were unbypassed. The late events were more frequent in persons with a maximal heart rate of 130 beats/min or less on treadmill exercise testing. No other clinical or treadmill variables added additional independent prognostic information.