High Risk Of Subsequent Death Research Articles

Impact of Comorbid Sleep-Disordered Breathing and Atrial Fibrillation on the Long-Term Outcome After Ischemic Stroke.

Sleep-disordered breathing (SDB) and atrial fibrillation (AF) are highly prevalent in patients with stroke and are recognized as independent risk factors for stroke. Little is known about the impact of comorbid SDB and AF on long-term outcomes after stroke. In this prospective cohort study, 353 patients with acute ischemic stroke or transient ischemic attacks were analyzed. Patients were screened for SDB by respiratory polygraphy during acute hospitalization. Screening for AF was performed using a 7-day ECG up to 3× in the first 6 months. Follow-up visits were scheduled at 1, 3, 12, 24, and 36 months poststroke. Cox regression models adjusted for various factors (age, sex, body mass index, hypertension, diabetes, dyslipidemia, and heart failure) were used to assess the impact of comorbid SDB and AF on subsequent death or cerebro-cardiovascular events. Among 353 patients (299 ischemic stroke and 54 transient ischemic attacks), median age, 67 (interquartile range, 57-74) years with 63% males. Moderate-to-severe SDB (apnea-hypopnea index score, ≥15/h) was present in 118 (33.4%) patients. Among the 56 (15.9%) patients with AF, 28 had comorbid moderate-to-severe SDB and AF. Over 36 months, there were 12 deaths and 67 recurrent cerebro-cardiovascular events. Patients with comorbid moderate-to-severe SDB and AF had a higher risk of subsequent death or cerebro-cardiovascular events compared with those with only moderate-to-severe SDB without AF (hazard ratio, 2.49 [95% CI, 1.18-5.24]) and to those without moderate-to-severe SDB or AF (hazard ratio, 2.25 [95% CI, 1.12-4.50]). However, no significant difference was found between the comorbid moderate-to-severe SDB and AF group and the group with only AF without moderate-to-severe SDB (hazard ratio, 1.64 [95% CI, 0.62-4.36]). Comorbid moderate-to-severe SDB and AF significantly increase the risk of long-term mortality or recurrent cerebro-cardiovascular events after acute ischemic stroke. Considering both conditions as cumulative and modifiable cerebro-cardiovascular risk factors is of interest for the management of acute stroke. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02559739.

Abstract 12307: Machine Learning Model Predicting Bleeding Risk in Patients With Coronary Artery Disease

Background: Bleeding complication during antiplatelet therapy for coronary artery disease (CAD) is an adverse issue due to high risk of subsequent death and cardiovascular events. Although many bleeding risk scores have been proposed, simple and personalized risk assessment in routine clinical practice is challenging because of the heterogeneous and multifactorial pathophysiological condition. We aimed to develop a machine learning-based risk prediction for bleeding events in CAD patients treated with antiplatelet therapy. Methods: This study was a retrospective, observational cohort study using the Japanese nationwide electronic medical record database. Data from 49,324 CAD patients who underwent revascularization and received antiplatelet therapy between July 2008 through July 2022 were randomly assigned to the model derivation and validation sets. Data balancing technique: synthetic minority over-sampling technique was used to process the imbalanced data. Risk prediction model was developed using random forest (RF) after feature selection by the Boruta algorithm. Outcome was defined as bleeding events requiring hospitalization. Results: Of all, 1,684 (3.4%) bleeding events were observed during study period. The area under the curves of receiver operator characteristics of RF (95% confidence intervals) for bleeding were 0.977 (0.976-0.978) in derivation and 0.975 (0.972-0.977) in validation set. The performance metrics of the model were well acceptable (accuracy, 0.939; precision, 0.990; recall, 0.887; F1-score 0.936, respectively) in validation set. The sigmoid calibrated RF models resulted in well approximating observed bleeding events in the calibration plot and the Brier score of 0.042. Conclusions: This machine learning model could predict bleeding risk for CAD patients treated with antiplatelet therapy in real-world setting.

Prevalence and prognostic impact of left ventricular systolic dysfunction or pulmonary congestion after acute myocardial infarction.

The aim was to describe the prevalence, characteristics, and outcome of patients with acute myocardial infarction (MI) developing left ventricular (LV) systolic dysfunction or pulmonary congestion by applying different criteria to define the population. In patients with MI included in the Swedish web-system for enhancement and development of evidence-based care in heart disease (SWEDEHEART) registry, four different sets of criteria were applied, creating four not mutually exclusive subsets of patients: patients with MI and ejection fraction (EF)<50% and/or pulmonary congestion (subset 1); EF<40% and/or pulmonary congestion (subset 2); EF<40% and/or pulmonary congestion and at least one high-risk feature (subset 3, PARADISE-MI like); and EF<50% and no diabetes mellitus (subset 4, DAPA-MI like). Subsets 1, 2, 3, and 4 constituted 31.6%, 15.0%, 12.8%, and 22.8% of all patients with MI (n=87177), respectively. The age and prevalence of different co-morbidities varied between subsets. For median age, 70 to 77, for diabetes mellitus, 22 to 33%; for chronic kidney disease, 22 to 38%, for prior MI, 17 to 21%, for atrial fibrillation, 7 to 14%, and for ST-elevations, 38 to 50%. The cumulative incidence of death or heart failure hospitalization at 3years was 17.4% (95% CI: 17.1-17.7%) in all MIs; 26.9% (26.3-27.4%) in subset 1; 37.6% (36.7-38.5%) in subset 2; 41.8% (40.7-42.8%) in subset 3; and 22.6% (22.0-23.2%) in subset 4. Depending on the definition, LV systolic dysfunction or pulmonary congestion is present in 13-32% of all patients with MI and is associated with a two to three times higher risk of subsequent death or HF admission. There is a need to optimize management and improve outcomes for this high-risk population.

Contemporary outpatient management of patients with worsening heart failure with reduced ejection fraction: Rationale and design of the CHART-HF study

Patients with heart failure with reduced ejection fraction (HFrEF) and worsening HF events (WHFE) represent a distinct subset of patients with a substantial comorbidity burden, greater potential for intolerance to medical therapy, and high risk of subsequent death, hospitalization and excessive healthcare costs. Although multiple therapies have been shown to be efficacious and safe in this high-risk population, there are limited real-world data regarding factors that impact clinical decision-making when initiating or modifying therapy. Likewise, prior analyses of US clinical practice support major gaps in medical therapy for HFrEF and few medication changes during longitudinal follow-up, yet granular data on reasons why clinicians do not initiate or up-titrate guideline-directed medication are lacking. We designed the CHART-HF study, an observational study of approximately 1,500 patients comparing patients with and without WHFE (WHFE defined as receipt of intravenous diuretics in the inpatient, outpatient, or emergency department setting) who had an index outpatient visit in the US between 2017 and 2019. Patient-level data on clinical characteristics, clinical outcomes, and therapy will be collected from 2 data sources: a single integrated health system, and a national panel of cardiologists. Furthermore, clinician-reported rationale for treatment decisions and the factors prioritized with selection and optimization of therapies in real-world practice will be obtained. To characterize elements of clinician decision-making not documented in the medical record, the panel of cardiologists will review records of patients seen under their care to explicitly note their primary reason for initiating, discontinuing, and titrating medications specific medications, as well as the reason for not making changes to each medication during the outpatient visit. Results from CHART-HF have the potential to detail real-world US practice patterns regarding care of patients with HFrEF with versus without a recent WHFE, to examine clinician-reported reasons for use and non-use of guideline-directed medical therapy, and to characterize the magnitude and nature of clinical inertia toward evidence-based medication changes for HFrEF.

New-onset atrial fibrillation in patients with worsening heart failure and coronary artery disease: an analysis from the COMMANDER-HF trial.

Atrial fibrillation (AF) in the presence of heart failure (HF) is associated with poor outcomes including a high-risk of stroke and other thromboembolic events. Identifying patients without AF who are at high-risk of developing this arrhythmia has important clinical implications. To develop a risk score to identify HF patients at high risk of developing AF. The COMMANDER-HF trial enrolled 5022 patients with HF and a LVEF ≤ 40%, history of coronary artery disease, and absence of AF at baseline (confirmed with an electrocardiogram). Patients were randomized to either rivaroxaban (2.5mg bid) or placebo. New-onset AF was confirmed by the investigator at study visits. 241 (4.8%) patients developed AF during the follow-up (median 21months). Older age (≥ 65years), LVEF < 35%, history of PCI or CABG, White race, SBP < 110mmHg, and higher BMI (≥ 25kg/m2) were independently associated with risk of new-onset AF, whereas the use of DAPT was associated with a lower risk of new-onset AF. We then built a risk score from these variables (with good accuracy C-index = 0.71) and calibration across observed and predicted tertiles of risk. New-onset AF events rates increased steeply by increasing tertiles of the risk-score. Compared to tertile 1, the risk of new-onset AF was 2.5-fold higher in tertile 2, and 6.3-fold higher in tertile 3. Rivaroxaban had no effect in reducing new-onset AF. In time-updated models, new-onset AF was associated with a higher risk of subsequent all-cause death: HR (95%CI) 1.38 (1.11-1.73). A well-calibrated risk-score identified patients at risk of new-onset AF in the COMMANDER-HF trial. Patients who developed AF had a higher risk of subsequent death. Risk of new-onset atrial fibrillation in patients with HFrEF and coronary artery disease.

Prevalence and prognostic value of elevated troponins in patients hospitalised for coronavirus disease 2019: a systematic review and meta-analysis

BackgroundThe clinical significance of cardiac troponin measurement in patients hospitalised for coronavirus disease 2019 (covid-19) is uncertain. We investigated the prevalence of elevated troponins in these patients and its prognostic value for predicting mortality.MethodsStudies were identified by searching electronic databases and preprint servers. We included studies of hospitalised covid-19 patients that reported the frequency of troponin elevations above the upper reference limit and/or the association between troponins and mortality. Meta-analyses were performed using random-effects models.ResultsFifty-one studies were included. Elevated troponins were found in 20.8% (95% confidence interval [CI] 16.8–25.0 %) of patients who received troponin test on hospital admission. Elevated troponins on admission were associated with a higher risk of subsequent death (risk ratio 2.68, 95% CI 2.08–3.46) after adjusting for confounders in multivariable analysis. The pooled sensitivity of elevated admission troponins for predicting death was 0.60 (95% CI 0.54–0.65), and the specificity was 0.83 (0.77–0.88). The post-test probability of death was about 42% for patients with elevated admission troponins and was about 9% for those with non-elevated troponins on admission. There was significant heterogeneity in the analyses, and many included studies were at risk of bias due to the lack of systematic troponin measurement and inadequate follow-up.ConclusionElevated troponins were relatively common in patients hospitalised for covid-19. Troponin measurement on admission might help in risk stratification, especially in identifying patients at high risk of death when troponin levels are elevated. High-quality prospective studies are needed to validate these findings.Systematic review registrationPROSPERO CRD42020176747

Prevalence and prognostic impact of left ventricular systolic dysfunction after acute myocardial infarction

Abstract Background Left ventricular dysfunction after an acute myocardial infarction (MI) is associated with poor outcome. The PARADISE-MI trial is examining whether an angiotensin receptor-neprilysin inhibitor reduces the risk of cardiovascular death or worsening heart failure (HF) in this population. The aim of this study was to examine the prevalence and prognosis of different subsets of post-MI patients in a real-world setting. Additionally, the prognostic importance of some common risk factors used as risk enrichment criteria in the PARADISE-MI trial were specifically examined. Methods In a nationwide myocardial infarction registry (SWEDEHEART), including 87 177 patients with type 1 MI between 2011–2018, 3 subsets of patients were identified in the overall MI cohort (where patients with previous HF were excluded); population 1 (n=27 568 (32%)) with signs of acute HF or an ejection fraction (EF) &amp;lt;50%, population 2 (n=13 038 (15%)) with signs of acute HF or an EF &amp;lt;40%, and population 3 (PARADISE-MI like) (n=11 175 (13%)) with signs of acute HF or an EF &amp;lt;40% and at least one risk factor (Age ≥70, eGFR &amp;lt;60, diabetes mellitus, prior MI, atrial fibrillation, EF &amp;lt;30%, Killip III-IV and STEMI without reperfusion therapy). Results When all MIs, population 1 (HF or EF &amp;lt;50%), 2 (HF or EF &amp;lt;40%) and 3 (HF or EF &amp;lt;40% + additional risk factor (PARADISE-MI like)) were compared, the median (IQR) age increased from 70 (61–79) to 77 (70–84). Also, the proportion of diabetes (22% to 33%), STEMI (38% to 50%), atrial fibrillation (10% to 24%) and Killip-class &amp;gt;2 (1% to 7%) increased. After 3 years of follow-up, the cumulative probability of death or readmission because of heart failure in the overall MI population and in population 1 to 3 was 17.4%, 26.9%, 37.6% and 41.8%, respectively. In population 2, all risk factors were independently associated with death or readmission because of HF (Age ≥70 (HR (95% CI): 1.80 (1.66–1.95)), eGFR &amp;lt;60 (1.62 (1.52–1.74)), diabetes mellitus (1.35 (1.26–1.44)), prior MI (1.16 (1.07–1.25)), atrial fibrillation (1.35 (1.26–1.45)), EF &amp;lt;30% (1.69 (1.58–1.81)), Killip III-IV (1.34 (1.19–1.51)) and STEMI without reperfusion therapy (1.34 (1.21–1.48))) in a multivariable Cox regression analysis. The risk increased with increasing number of risk factors (Figure 1). Conclusion Depending on definition, post MI HF is present in 13–32% of all MI patients and is associated with a high risk of subsequent death or readmission because of HF. The risk increases significantly with every additional risk factor. There is a need to optimize management and improve outcomes for this high risk population. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novartis

Prognostic value of NT-proBNP, and echocardiographic indices of diastolic function, in hospitalized patients with acute heart failure and preserved left ventricular ejection fraction

BackgroundSeveral parameters have proven useful in assessing prognosis in outpatients with heart failure with preserved ejection fraction (HFpEF). In contrast, prognostic determinants in HFpEF hospitalized for an acute event are poorly investìgated. AimTo determine the predictive value of NT-proBNP, and diastolic function (assessed by E/e’), in patients with HFpEF hospitalized for acute heart failure. Methods and resultsWe evaluated 205 consecutive HFpEF patients admitted for acute heart failure (median age: 76[53,81], 36% male, median EF: 61 [54,77]). We assessed clinical, echocardiographic, and NT-proBNP values, on admission and at discharge. Primary end-point was the composite of all-cause death and/or HF rehospitalization.After a mean follow up of 28±10 months, 82 patients met the primary end-point; there were 30 deaths (14.6%), and 72 patients (35%) were rehospitalized for HF. By multivariable analysis, predictors of the composite end-point were: discharge E/e´ ≥14 (HR: 4.63 CI 95%: 2.71-18.2, p<0.0001), discharge NT-proBNP ≥1500 pg/ml (HR: 5.23, CI 95%: 2.87–17.8, p < 0.0001), ≥50% NT-proBNP decrease between admission and discharge (HR: 0.62, CI 95%: 0.25-0.79, p = 0.019). Combining E/e´ and NT-proBNP values at discharge further and significantly improved discrimination power compared to each variable analyzed separately (AUC, NT-proBNP at discharge: 0.80; E/e´ at discharge: 0.77; E/e´ + NT-proBNP: 0.88; p < 0.01). ConclusionsIn HFpEF patients hospitalized with acute heart failure, assessment of E/e´ ratio and NT-proBNP at discharge provides prognostic information on top of other variables, and allows to easily identify a population at higher risk of subsequent death or rehospitalization for heart failure, during a medium-term follow up.

Incidence, predictors and prognosis of new-onset cancer after hospital discharge for acute coronary syndrome

Introduction and objectivesThe concurrence of cancer and ischemic heart disease is a controversial issue, given the confluence of risk factors for both diseases. The aim of this study is to analyze the incidence, predictors, and prognosis of new-onset cancer after an acute coronary syndrome (ACS). MethodsRetrospective multicenter registry that includes 3867 consecutive patients discharged for ACS without a known history of cancer, from 2011 to 2015. The association between clinical variables and cancer occurrence was assessed by Fine-Gray proportional hazards regression analysis, and its prognostic impact was evaluated using Cox and Fine-Gray regression models. ResultsThe cumulative incidence of cancer was 2.47 per 100 patient/years. Four independent predictors of follow-up cancer were identified: age, male sex, smoking, and human immunodeficiency virus infection. We have constructed a simple risk score, based on the coefficients of these variables in the final multivariable model. Using this score, we stratified our population according to the risk of developing cancer: low (1.03% per year), moderate (2.35% per year), and high-risk (10.51% per year) groups. Post-discharge cancer was independently associated with an increased risk of non-cardiovascular death (HR, 17.65; 95%CI, 10.47–29.76) and bleeding (sHR, 2.54; 95%CI, 1.21–5.34), but not with reinfarction (sHR, 0.50; 95%CI, 0.16–1.56). ConclusionsCancer occurrence after hospital discharge for ACS is relatively low, but it could be predicted by the combination of 4 easily available clinical risk factors: age, male sex, smoking, and human immunodeficiency virus infection. Post-discharge cancer is associated with a higher risk of subsequent death and bleeding events.

Association of global and disease-specific health status with outcomes following continuous-flow left ventricular assist device implantation

BackgroundThe prognostic value of heart failure specific and global health status before and after left ventricular assist device (LVAD) implantation in the usual care setting is not well studied.MethodsWe included 3,836 continuous-flow LVAD patients in the INTERMACS registry. Health status was measured pre-operatively and 3 months post-LVAD using the Kansas City Cardiomyopathy Questionnaire (KCCQ) and EuroQol visual analog scale (VAS). Primary outcomes were mortality/rehospitalization. Inverse propensity weighting was used to minimize bias from missing data.ResultsPre-operative global and heart failure-specific health status were very poor: KCCQ median 34.6 (IQR 21.4-50.5); VAS median 43 (interquartile range (IQR) 25–65). Health status measures improved 3 months after LVAD placement: KCCQ median 69.3 (IQR 54.2-82.3); VAS median 75 (IQR 60–85). Pre-operative health status was not associated with death (unadjusted HR for lowest vs. highest score quartiles: 1.09 (0.85-1.41) KCCQ; 1.12 (0.85-1.49) VAS) or rehospitalization (unadjusted HR 0.83 (0.72-0.96) KCCQ; 0.99 (0.85-1.16) VAS). Three-month KCCQ was associated with mortality (unadjusted HR 2.17 (1.47-3.21); VAS was not (1.43 (0.94-2.17). Three-month KCCQ added incremental discriminatory value to the HeartMate II Risk Score for death (c-stat 0.60 to 0.66); VAS did not (c-stat 0.59 to 0.60). Three-month health status was associated with rehospitalization (unadjusted HR 1.31 (1.15-1.57) KCCQ; 1.24 (1.05-1.46) VAS), but did not add incremental discriminatory value (c-stat 0.52 to 0.55 and 0.54, respectively).ConclusionsThese real-world data suggest that pre-operative health status has limited association with outcomes after LVAD. However, persistently low health status after surgery may independently signal higher risk for subsequent death. Further study is needed to determine the clinical utility of routinely collected health status data after LVAD implantation.

The Hospitalization Burden and Post-Hospitalization Mortality Risk in Heart Failure With Preserved Ejection Fraction: Results From the I-PRESERVE Trial (Irbesartan in Heart Failure and Preserved Ejection Fraction)

ObjectivesThe aim of this study was to investigate prognosis in patients with heart failure (HF) with preserved ejection fraction and the causes of hospitalization and post-hospitalization mortality. BackgroundAlthough hospitalizations in patients with HF with preserved ejection fraction are common, there are limited data from clinical trials on the causes of admission and the influence of hospitalizations on subsequent mortality risk. MethodsPatients (n = 4,128) with New York Heart Association functional class II to IV HF and left ventricular ejection fractions >45% were enrolled in I-PRESERVE (Irbesartan in Heart Failure and Preserved Ejection Fraction). A blinded events committee adjudicated cardiovascular hospitalizations and all deaths using predefined and standardized definitions. The risk for death after HF, any-cause, or non-HF hospitalization was assessed using time-dependent Cox proportional hazard models. ResultsA total of 2,278 patients had 5,863 hospitalizations during the 49 months of follow-up, of which 3,585 (61%) were recurrent hospitalizations. For any-cause hospitalizations, 26.5% of patients died during follow-up, with an incident mortality rate of 11.1 deaths per 100 patient-years (PYs) and an adjusted hazard ratio of 5.32 (95% confidence interval: 4.21 to 6.23). Overall, 53.6% of hospitalizations were classified as cardiovascular and 43.7% as noncardiovascular, with 2.7% not classifiable. HF was the largest single cause of initial (17.6%) and overall (21.1%) hospitalizations, although, after HF hospitalization, a substantially higher proportion of readmissions were due to primary HF causes (40%). HF hospitalization occurred in 685 patients, with 41% deaths during follow-up, an incident mortality rate of 19.3 deaths per 100 PYs. The adjusted hazard ratio was 2.93 (95% confidence interval: 2.40 to 3.57) relative to patients who were not hospitalized for HF and was greater in those with longer durations of hospitalization. There were 1,593 patients with only non-HF hospitalizations, 21% of whom died during follow-up, with an incident mortality rate of 8.7 deaths per 100 PYs and an adjusted hazard ratio of 4.25 (95% confidence interval: 3.27 to 5.32). The risk for death was highest in the first 30 days and declined over time for all hospitalization categories. Patients not hospitalized for HF or for any cause had observed incident mortality rates of 3.8 and 1.3 deaths per 100 PYs, respectively. ConclusionsIn I-PRESERVE, HFpEF patients hospitalized for any reason, and especially for HF, were at high risk for subsequent death, particularly early. The findings support the need for careful attention in the post-discharge time period including attention to comorbid conditions. Among those hospitalized for HF, the high mortality rate and increased proportion of readmissions due to HF (highest during the first 30 days), suggest that this group would be an appropriate target for investigation of new interventions.

High sensitivity C-reactive protein and cardfiac resynchronization therapy in patients with advanced heart failure.

BackgroundThe data on the prognostic values of high sensitivity C-reactive protein (hsCRP) levels in patients with advanced symptomatic heart failure (HF) receiving cardiac resynchronization therapy (CRT) are scarce. The aim of present study was to investigate the association of serum hsCRP levels with left ventricle reverse remodeling after six months of CRT as well as long-term outcome.MethodsA total of 232 CRT patients were included. The assessment of hsCRP values, clinical status and echocardiographic data were performed at baseline and after six months of CRT. Long-term follow-up included all-cause mortality and hospitalizations for HF.ResultsDuring the mean follow-up periods of 31.3 ± 31.5 months, elevated hsCRP (> 3 mg/L) prior to CRT was associated with a significant 2.39-fold increase (P = 0.006) in the risk of death or HF hospitalizations. At 6-month follow-up, patients who responded to CRT showed significant reductions or maintained low in hsCRP levels (–0.5 ± 4.1 mg/L reduction) compared with non-responders (1.7 ± 6.1 mg/L increase, P = 0.018). Compared with patients in whom 6-month hsCRP levels were reduced or remained low, patients in whom 6-month hsCRP levels were increased or maintained high experienced a significantly higher risk of subsequent death or HF hospitalizations (Log-rank P < 0.001). The echocardiographic improvement was also better among patients in whom 6-month hsCRP levels were reduced or remained low compared to those in whom 6-month hsCRP levels were raised or maintained high.ConclusionsOur findings demonstrated that measurement of baseline and follow-up hsCRP levels may be useful as prognostic markers for timely potential risk stratification and subsequent appropriate treatment strategies in patients with advanced HF undergoing CRT.

Does plasma transfusion portend pulmonary dysfunction? A tale of two ratios

An unresolved concern regarding resuscitation in the setting of massive hemorrhage is potential lung injury from the transfusion of relatively more plasma-rich components. However, the association between plasma-to-packed red blood cell (PRBC) ratio and subsequent pulmonary dysfunction remains unclear. The purpose of this study was to evaluate the impact of plasma/PRBC on PaO2-to-FIO2 (P/F) ratio in the setting of massive transfusion (MT). During a 5.5-year period, prospective data were collected on trauma patients who underwent MT, defined as 10 or more units of PRBC transfusion by completion of hemorrhage control. Deaths within 48 hours of arrival were excluded. Acute lung injury (ALI) and adult respiratory distress syndrome (ARDS) were defined as P/F ratio of less than 300 and less than 200 at 48 hours, respectively. Stepwise multiple regression analysis was performed to determine variables significantly associated with P/F ratio. A total of 199 patients met inclusion criteria; 159 (80%) developed ALI, and 105 (53%) developed ARDS. ALI and ARDS were both associated with subsequent mortality: ARDS at 24% versus no ARDS at 10% (p < 0.05) and ALI at 21% versus no ALI at 2.5% (p < 0.05). Paradoxically, patients with P/F ratio of 300 or greater were found to have received more plasma (5.6 U vs. 4.3 U, p < 0.05) and higher plasma-to-PRBC ratio (1:2 vs. 1:3, p < 0.05) at completion of hemorrhage control. Stepwise multiple regression analysis, however, identified age (p < 0.001) and chest Abbreviated Injury Scale (AIS) score (p = 0.04), but not plasma/PRBC (p = 0.10), to be independent determinants of P/F ratio at 48 hours. In this cohort of MT patients who survived beyond the first 48 hours, pulmonary dysfunction developed in the majority and was associated with a 10-fold higher risk of subsequent death. However, plasma-to-RBC ratio achieved during hemorrhage control had neither a positive nor a negative impact on subsequent P/F ratio. In fact, only unalterable patient factors including age and severity of thoracic injury were associated with subsequent P/F ratio. Prognostic study, level III.

Abstract 18607: Prevalence, Outcome, and Predictors of Cardio-Renal Syndrome in Children with Dilated Cardiomyopathy

Background: Cardio-renal syndrome (CRS) describes variety of acute or chronic conditions where the primary failing organ can be either the heart or kidney. The prevalence, predictors and outcome of CRS has not been reported in children with dilated cardiomyopathy (DCM). Methodology: Data from patients &gt; 1 year of age with DCM enrolled in the Pediatric Cardiomyopathy Registry (PCMR) was assessed. CRS was defined as glomerular filtration rate &lt;90 ml/min/1.73m 2 estimated by modified Schwartz formula (eGFR). Patients with eGFR&gt;150 ml/min/1.73m 2 were excluded. CRS prevalence was determined by cross-sectional design in patients newly diagnosed with DCM using the baseline PCMR data. Survival analysis compared patients with vs. without CRS using annual PCMR data. Regression models were applied on both baseline and annual data to study the interactions between eGFR and different echocardiographic measures. Results: The baseline data had 484 children with DCM. Serum Cr data to calculate eGFR were available for 92 patients. Fifty six (62.0%) patients had eGFR &lt; 90 ml/min/1.73m 2 , which is greater than the 48% prevalence published in 3256 healthy historical controls (P&lt;0.001). CRS patients had a mean eGFR of 61 (±22.6) vs. 108 (±14) (P&lt;0.001). Death occurred in 8 (14%) of CRS patients compared to no deaths in patients without CRS (P=0.052) after 7 years follow-up. Univariate regression models showed a significant positive correlation between fractional shortening (FS) and eGFR (P= 0.0013, r 2 = 0.09). No correlation was observed between eGFR and ejection fraction (EF), left ventricular end-diastolic dimension (LVEDD) and LVEDD Z-scores. Conclusion: This is the first study to show that CRS is common in children newly diagnosed with DCM and is associated with higher risk of subsequent death. Worsening FS was associated with decreasing eGFR which suggests that patients with poor FS might have significant CRS. We suggest kidney functions should be evaluated systematically in children with DCM to assess for chronic kidney disease and direct potential management.

Factors associated with infant death after apparent life-threatening event (ALTE)

To detect factors associated with greater risk of death in infants after an apparent life-threatening event (ALTE). This cross-sectional, retrospective, descriptive and analytic study evaluated infants younger than 12 months who had a sudden event of cyanosis, pallor, hypotonia or apnea and were seen in the emergency department of a tertiary university hospital. Forward stepwise logistic regression (Wald) was used to calculate and adjust odds ratios to evaluate associations. Mean age of the 145 patients included in the study was 105 days (median = 65 days). Eleven (7.6%) died, and their mean age was 189 days (median = 218 days). Mean age of survivors was 98 days (median = 62 days) (p = 0.003). Activity before the event, prematurity and number of events were not associated with death. A significant association was found with pallor. Of the 11 infants, 3 had spontaneous resolution of ALTE, whereas 8 patients [27.6%; p < 0.001; OR = 14.3 (95%CI 3.51-58.3)] did not. The associations with respiratory or cardiovascular disease were also significant. In multivariate analysis, immediate spontaneous resolution [p = 0.015; OR = 6.06 (95%CI 1.02-35.94)] and diagnosis of cardiovascular disease [p = 0.047; OR = 164.27 (95%CI 7.34-3.673.78)] remained statistically significant. Infants who experienced an ALTE had a higher risk of subsequent death when their age was greater than 6 months and the event had a long duration, particularly when ALTE was associated with cardiovascular disease.

Risk prediction by heart rate turbulence and deceleration capacity in postinfarction patients with preserved left ventricular function retrospective analysis of 4 independent trials

Background and aim In the Improved Stratification of Autonomic Regulation–Risk trial, postinfarction patients with severe autonomic failure (SAF)—defined as abnormal heart rate turbulence in the presence of abnormal deceleration capacity (DC)—were at high risk of subsequent death, even if left ventricular function was not particularly compromised. The aim of this study was to investigate SAF as a risk predictor in independent postinfarction cohorts. Methods and results The data of 3 postinfarction trials (ie, St George's Hospital Medical School Postinfarction Survey, Holter substudy of the European Myocardial Infarction Amiodarone Trial with both the placebo and the amiodarone arms, and Multiple Risk Factor Analysis Trial) were reanalyzed in a blinded fashion. The populations included a total of 2534 postinfarction patients. Heart rate turbulence and DC were obtained from 24-hour Holter recordings. Patients with both abnormal heart rate turbulence (slope ≤2.5 ms/R-R and onset ≥0%) and abnormal DC (≤4.5 milliseconds) were considered suffering from SAF and prospectively classified as high risk. Primary end point was all-cause mortality. During follow-up, 291 of 2534 patients died. In all populations, SAF was a highly significant predictor of death in the subgroups of patients with preserved left ventricular ejection fraction (LVEF; >30%). The mortality risk of these patients was not statistically different from that of patients with impaired LVEF (≤30%). The combined use of the criteria, LVEF of 30% or less and LVEF of more than 30% as well as SAF lead to a significant increase of sensitivity in all populations, whereas the positive predictive accuracies were preserved. Conclusion In postinfarction patients with preserved left ventricular function, SAF identifies a subgroup with increased mortality risk equivalent to patients with LVEF of 30% or less.

Abstract 2036: Severe Autonomic Failure in Diabetic Postinfarction-Patients

Background: Diabetic post-infarction patients are at high risk of subsequent death. Deceleration Capacity (DC) and Heart Rate Turbulence (HRT) are a risk predictors that quantify different aspects of autonomic performance (tone and reflex function). Sever Autonomic Failure (SAF) was assumed if DC and HRT were compromised. This study investigates the predictive value SAF in diabetic post-infarction patients. Patients: 416 consecutive diabetic post-infarction patients, age &lt; &lt;26&gt; 75 years, in sinus rhythm were enrolled. Primary endpoint was total mortality at 5 years. Mean follow-up period was 4.4 years. Methods: DC and HRT were determined according to the published methodology. Severe autonomic failure (SAF) was defined as DC &lt; &lt;26&gt; 4.5 ms and HRT category 2. Cox-proportional hazards analyses were performed with respect to age, history of previous myocardial infarction, mean heart rate, HRV index and arrhythmia count during 24-h Holter monitoring, QRS duration and LVEF, all with prospectively defined dichotomies. Results: During follow-up, 61 patients died. There were 36 cardiac deaths, out of which 23 occurred suddenly. 24 patients presented with SAF, 13 patients with LVEF &lt; &lt;26&gt; 30%. Five-year all-cause mortality rates of patients with and without SAF were 63% and 11%, respectively (Figure , left panel). For LVEF 30%, these figures were 51% and 15% (Figure , right panel). Similar figures were observed for cardiac mortality. In multivariable analysis, presence of SAF indicated a hazard ratio of 5.1 (LVEF 4.2; age 3.5, mean heart rate 1.9). Conclusion: Diabetic post-infarction patients with SAF have a poor outcome, whereas mortality rates of patients without SAF were low.

Impact of Relapse after Allogeneic Hematopoietic Stem Cell Transplant on Subsequent Outcome in Patients with Chronic Myeloid Leukemia: A Better Understanding through Multi-State Modeling.

Donor lymphocyte infusions and imatinib have been the mainstay of treatment for chronic myeloid leukemia (CML) patients relapsing after allogeneic hematopoietic stem cell transplantation (alloSCT) in recent years. Improvements in transplant related mortality and a reduction of lethal infections have been documented. No comprehensive data are yet available about the impact of relapse (REL) itself on survival and a possible improvement over calendar time.We analyzed 13418 patients with CML transplanted between 1980 and 2003 (60% male, median age 36 years [range 0–71]) from an allogeneic donor (65% HLA identical sibling, 1% twin, 7% other related, and 27% unrelated). Of those, 2558 (19%) were reported with REL.We investigated the impact of REL on death rate in 4 periods: A [1980–92], B [1993–96], C [1997–99] and D [2000–03], adjusting for other factors. We applied a series of Cox models where REL was used as a time-depending covariate and where we used an integrated approach in the framework of multi-state models, with REL representing an intermediate event in a patient's post-transplantation history. We used the EBMT risk score as a propensity score to adjust for intrinsic differences in survival over calendar time and Calendar time as categorical factor to assess trends.REL increased death rate over the whole observation period. However, there was a significant improvement over the years: death hazard ratio (HR) decreased from 4.5 to 3.2, 2.7 and 2.4 for the periods A, B, C and D, respectively. The impact of REL on death rate was also influenced by the EBMT risk score [HR 1, 1.9, and 3.5 for low, intermediate, and high risk score, respectively]. We investigated, with the same methodology used above, the impact of REL on death rate in a subset of 1977 patients transplanted after 1992 and with known information on the type of relapse at its first evidence (molecular/cytogenetic [M-REL] or hematological [H-REL]). The M-REL/H-REL ratio increases over the years (1.1, 1.2, and 2.5 in periods B, C, and D, respectively). Results confirmed that the impact of REL on death rate decreases over the years, but hardly and not significantly for H-REL (HRs around 6 in periods B, C, D) and more pronounced and significantly for the M-REL (HRs 0.68, 0.52, and 0.12 in periods B, C, and D, respectively). It is notable that H-REL was associated with higher death rate, M-REL with lower.We have shown that:REL after alloSCT for CML is associated with a higher risk for subsequent death;the effect of REL on death rate is decreasing in more recent years;the effect of REL on death rate depends on the type of REL (H-REL or M-REL) and the EBMT risk score;an integrated approach like multi-state modeling is flexible and allows clinically relevant interpretations.Our findings suggest that the effect of REL on death rate is decreasing in more recent years, mainly because of the increasing proportion of patients in whom REL is first detected at pre-clinical level (ie. molecular/cytogenetic relapse). Our results will form the basis for future description and characterization of patient groups in comparative retrospective analyses and prospective trials.

P5-32: Impact of gender on the predictive power of heart rate turbulence

Heart Rate Turbulence (HRT) is a strong ECG based risk predictor after acute myocardial infarction (MI). HRT quantifies the baroreflex-mediated oscillation of heart rate following singular ventricular premature complexes (VPC). Blunted HRT indicates high risk for subsequent death. Aim of this study was to search for gender-related differences in HRT.

Valsartan

Valsartan (Diovan) is an oral angiotensin II-receptor antagonist with specificity for the angiotensin II type 1 receptor subtype. It demonstrates antihypertensive activity and slows the progression of chronic heart failure (CHF). Recently it has been evaluated in comparison with an ACE inhibitor regimen in patients with heart failure or left ventricular systolic dysfunction (LVSD) after an acute myocardial infarction (MI), a population known to be at high risk of subsequent death or other major cardiovascular events. In the VALIANT (VALsartan In Acute myocardial iNfarcTion) trial, valsartan was as effective as captopril at reducing mortality and cardiovascular morbidity in patients who developed heart failure and/or LVSD after surviving an MI. It was also generally well tolerated in this population. Treatment with a combination of valsartan plus captopril provided no additional therapeutic benefit over treatment with captopril and was less well tolerated. Valsartan has a potential role as a new treatment for high-risk patients in the post-MI setting.