Badira F. Makhoul

Elevated red cell distribution width predicts poor outcome in young patients with community acquired pneumonia

IntroductionCommunity acquired pneumonia (CAP) is a major cause of morbidity and mortality. While there is much data about risk factors for severe outcome in the general population, there is less focus on younger group of patients. Therefore, we aimed to detect simple prognostic factors for severe morbidity and mortality in young patients with CAP.MethodsPatients of 60 years old or younger, who were diagnosed with CAP (defined as pneumonia identified 48 hours or less from hospitalization) between March 1, 2005 and December 31, 2008 were retrospectively analyzed for risk factors for complicated hospitalization and 90-day mortality.ResultsThe cohort included 637 patients. 90-day mortality rate was 6.6% and the median length of stay was 5 days. In univariate analysis, male patients and those with co-morbid conditions tended to have complicated disease. In multivariate analysis, variables associated with complicated hospitalization included post chest radiation state, prior neurologic damage, blood urea nitrogen (BUN) > 10.7 mmol/L and red cell distribution width (RDW) > 14.5%; whereas, variables associated with an increased risk of 90-day mortality included age ≥ 51 years, prior neurologic damage, immunosuppression, and the combination of abnormal white blood cells (WBC) and elevated RDW. Complicated hospitalization and mortality rate were significantly higher among patients with increased RDW regardless of the white blood cell count. Elevated RDW was associated with a significant increase in complicated hospitalization and 90-day mortality rates irrespective to hemoglobin levels.ConclusionsIn young patients with CAP, elevated RDW levels are associated with significantly higher rates of mortality and severe morbidity. RDW as a prognostic marker was unrelated with hemoglobin levels.Trial registrationClinicalTrials.Gov NCT00845312

Relation between changes in red cell distribution width and clinical outcomes in acute decompensated heart failure

BACKGROUND Increased red blood cell distribution (RDW) has been associated with adverse outcomes in patients with heart failure. We studied the association between baseline RDW and changes in RDW during hospital course with clinical outcomes in acute decompensated heart failure (ADHF) patients. METHODS AND RESULTS We prospectively studied 614 patients with ADHF. Baseline RDW and RDW change during hospital course were determined. The relationship between RDW and clinical outcomes after hospital discharge was tested using Cox regression models, adjusting for clinical characteristics, echocardiographic findings and brain natriuretic peptide levels. During follow up (1 year), 286 patients (46.6%) died and 84 were readmitted for ADHF (13.7%). Median RDW was significantly higher among patients who died compared to patients who survived (15.6% interquartile range [14.5 to 17.1] vs. 14.9% mg/L interquartile range [14.1 to 16.1], P<0.0001). Compared with patients in the 1st RDW quartile, the adjusted hazard ratio [HR] for death or rehospitalization was 1.9 [95% CI 1.3-2.6] in patients in the 4th quartile. Changes in RDW during hospitalization were strongly associated with changes in mortality risk. Compared with patients with persistent normal RDW (<14.5%), the adjusted HR for mortality was 1.9 [95% CI 1.1-3.1] for patients in whom RDW increased above 14.5% during hospital course, similar to patients with persistent elevation of RDW (HR was 1.7, 95% CI 1.2-2.3). CONCLUSION In patients hospitalized with ADHF, RDW is a strong independent predictor of greater morbidity and mortality. An increase in RDW during hospitalization also portends adverse clinical outcome.

Pulmonary Hypertension, Right Ventricular Function, and Clinical Outcome in Acute Decompensated Heart Failure

BACKGROUND Pulmonary hypertension (PH) and right ventricular (RV) dysfunction have been associated with adverse outcome in patients with chronic heart failure. However, data are lacking in the setting of acute decompensated heart failure (ADHF). We sought to determine prognostic significance of PH in patients with ADHF and its interaction with RV function. METHODS We studied 326 patients with ADHF. Pulmonary artery systolic pressure (PASP) and RV function were determined with the use of Doppler echocardiography, with PH defined as PASP >50 mm Hg. The primary end point was all-cause mortality during 1-year follow-up. RESULTS PH was present in 139 patients (42.6%) and RV dysfunction in 83 (25.5%). The majority of patients (70%) with RV dysfunction had PH. Compared with patients with normal RV function and without PH, the adjusted hazard ratio (HR) for mortality was 2.41 (95% confidence interval [CI] 1.44-4.03; P = .001) in patients with both RV dysfunction and PH. Patients with normal RV function and PH had an intermediate risk (adjusted HR 1.78, 95% CI 1.11-2.86; P = .016). Notably, patients with RV dysfunction without PH were not at increased risk for 1-year mortality (HR 1.04, 95% CI 0.43-2.41; P = .94). PH and RV function data resulted in a net reclassification improvement of 22.25% (95% CI 7.2%-37.8%; P = .004). CONCLUSIONS PH and RV function provide incremental prognostic information in ADHF. The combination of PH and RV dysfunction is particularly ominous. Thus, the estimation of PASP may be warranted in the standard assessment of ADHF.

Interaction Between Worsening Renal Function and Persistent Congestion in Acute Decompensated Heart Failure

Worsening renal function (WRF) and congestion are inextricably related pathophysiologically, suggesting that WRF occurring in conjunction with persistent congestion would be associated with worse clinical outcome. We studied the interdependence between WRF and persistent congestion in 762 patients with acute decompensated heart failure (HF). WRF was defined as ≥0.3 mg/dl increase in serum creatinine above baseline at any time during hospitalization and persistent congestion as ≥1 sign of congestion at discharge. The primary end point was all-cause mortality with mean follow-up of 15 ± 9 months. Readmission for HF was a secondary end point. Persistent congestion was more common in patients with WRF than in patients with stable renal function (51.0% vs 26.6%, p <0.0001). Both persistent congestion and persistent WRF were significantly associated with mortality (both p <0.0001). There was a strong interaction (p = 0.003) between persistent WRF and congestion, such that the increased risk for mortality occurred predominantly with both WRF and persistent congestion. The adjusted hazard ratio for mortality in patients with persistent congestion as compared with those without was 4.16 (95% confidence interval [CI] 2.20 to 7.86) in patients with WRF and 1.50 (95% CI 1.16 to 1.93) in patients without WRF. In conclusion, persisted congestion is frequently associated with WRF. We have identified a substantial interaction between persistent congestion and WRF such that congestion portends increased mortality particularly when associated with WRF.

Procalcitonin and interleukin 6 for predicting blood culture positivity in sepsis

BACKGROUND Procalcitonin and interleukin 6 (IL-6) are well-known predictors of blood culture positivity in patients with sepsis. However, the association of procalcitonin and IL-6 with blood culture positivity was assessed separately in previous studies. This study aims to examine and compare the performance of procalcitonin and IL-6, measured concomitantly, in predicting blood culture positivity in patients with sepsis. METHODS Forty adult patients with sepsis were enrolled in the study. Blood cultures were drawn before the institution of antibiotic therapy. The area under the curve (AUC) of the receiver operating characteristic curve was estimated to assess the performance of procalcitonin and IL-6 in predicting blood culture positivity. RESULTS Positive blood cultures were detected in 10 patients (25%). The AUC of procalcitonin and IL-6 was 0.85 and 0.61, respectively. The combined performance of procalcitonin and IL-6 was similar to that of procalcitonin alone, AUC of 0.85. On univariate analysis, only procalcitonin and IL-6 were associated with blood culture positivity. Multivariate logistic regression analysis showed that only procalcitonin was associated with blood culture positivity (odds ratio, 12.15 [1.29-114.0] for levels above the median compared with levels below the median). Using procalcitonin cut points of 1.35 and 2.14 (nanogram per milliliter) enabled 100% and 90% identification of positive blood cultures and reduced the need of blood cultures by 47.5% and 57.5%, respectively. CONCLUSIONS Compared with IL-6, procalcitonin better predicts blood culture positivity in patients with sepsis. Using a predefined procalcitonin cut points will predict most positive blood cultures and reduce the need of blood cultures in almost half of patients with sepsis.

Brain natriuretic peptide at discharge as a predictor of 6-month mortality in acute decompensated heart failure

BACKGROUND Brain natriuretic peptide (BNP) is well established in detecting acute decompensation of heart failure (ADHF). The role of BNP at discharge in predicting mortality is less established. Accumulating evidence suggests that inflammatory cytokines play an important role in the development of heart failure. We aimed to examine the contribution of BNP, interleukin 6, and procalcitonin to mortality in ADHF. METHODS A cohort of 33 patients with ADHF was identified between March 2009 and June 2010 at Rambam Health Care Campus, Haifa, Israel. The cohort was followed up for all-cause mortality during 6 months after hospital discharge. Cox proportional hazard model was used to assess the association between BNP, interleukin-6 and procalcitonin and all-cause mortality. RESULTS As compared to BNP at admission, BNP at discharge was more predictive for all-cause mortality. The area under the curve for BNP at admission and discharge was 0.810 (P=.004) and 0.864 (P=.001) respectively. Eleven patients (33.3%) patients who died during the follow-up period had higher BNP levels, median 2031.4 (IQR, 1173.4-2707.2), than those who survived; median 692.5 (IQR, 309.9-1159.9), (P = .001). On multivariate analysis, BNP remained an independent predictor for 6 month all-cause mortality HR 9.58 (95% CI, 2.0-45.89) for levels above the median compared to lower levels, (P=.005). Albumin, procalcitonin and interleukin 6 were not associated with all-cause mortality. CONCLUSIONS BNP at discharge is an independent predictor for all-cause mortality in patients with ADHF. Compared with BNP at admission, BNP at discharge has slightly higher predictive accuracy with regard to 6-month all-cause mortality.

Interleukin-6 at discharge predicts all-cause mortality in patients with sepsis

PURPOSE Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a central role in the pathogenesis of sepsis. We aim to investigate the association between IL-6 and all-cause mortality in patients with sepsis. METHODS A cohort of 40 elderly patients with sepsis was identified between March 2009 and June 2010 at Rambam Health Medical Campus, Haifa, Israel. The cohort was followed up for all-cause mortality occurring during the 6 months after hospital discharge. Cox proportional hazard model was used to assess the association between IL-6 and all-cause mortality. RESULTS Iinterleukin-6 at discharge had a higher predictive accuracy for all-cause mortality when compared with IL-6 at admission. The area under the curve was 0.752 (P = .015) and 0.545 (P = .661), respectively. Eleven (27.5%) patients died during follow-up; the subjects who died have higher IL-6 levels at discharge (median, 50.6 pg/mL [interquartile range, 39.6-105.9]) compared with survivors at the end of follow-up (median, 35.4 [interquartile range, 15.8-49]; P = .014). The risk of all-cause mortality was higher in subjects with IL-6 levels above the median compared with subjects with lower IL-6 levels (log-rank P = .017). On multivariate Cox proportional analysis, adjusting for the potential confounders, IL-6 at discharge remained an independent predictor for 6 month all-cause mortality (hazard ratio, 6.05 [1.24-24.20]) for levels above the median compared with lower levels. CONCLUSIONS Iinterleukin-6 at discharge is an independent predictor of all-cause mortality in patients with sepsis. Compared with IL-6 at admission, IL-6 at discharge better predicts all-cause mortality.

Dilated cardiomyopathy: an unusual complication of clozapine therapy

Background A 42-year-old obese man presented with acute pulmonary edema. He had a history of chronic residual schizophrenia for which he had been taking clozapine for 7 years, but had no known prior cardiac disease. Echocardiography demonstrated severe biventricular systolic and diastolic dysfunction with severe left ventricular enlargement. Cardiac catheterization showed no coronary artery disease.Investigations Physical examination, chest radiography, electrocardiography, transthoracic echocardiography, laboratory testing, viral serology, cardiac catheterization, coronary angiography and abdominal and renal ultrasonography.Diagnosis Clozapine-induced dilated cardiomyopathy.Management Intravenous nesiritide, furosemide and morphine followed by oral heart-failure therapy comprising ramipril, metoprolol succinate, spironolactone, and furosemide. Clozapine therapy was withdrawn.

Hyponatraemia predicts the acute (type 1) cardio-renal syndrome

The acute (type 1) cardio‐renal syndrome (CRS) refers to an acute worsening of heart function leading to worsening renal function (WRF), and frequently complicates acute decompensated heart failure (ADHF) and acute myocardial infarction (AMI). The aim of this study was to investigate whether hyponatraemia, a surrogate marker of congestion and haemodilution and of neurohormonal activation, could identify patients at risk for WRF.

Discordance Between Hemoconcentration and Clinical Assessment of Decongestion in Acute Heart Failure

INTRODUCTION Hemoconcentration has been proposed as a surrogate for successful decongestion in acute heart failure (AHF). The aim of the present study was to evaluate the relationship between hemoconcentration and clinical measures of congestion. METHODS AND RESULTS We studied 704 patients with AHF and volume overload. A composite congestion score was calculated at admission and discharge, with a score >1 denoting persistent congestion. Hemoconcentration was defined as any increase in hematocrit and hemoglobin levels between baseline and discharge. Of 276 patient with hemoconcentration, 66 (23.9%) had persistent congestion. Conversely, of 428 patients without hemoconcentration, 304 (71.0%) had no clinical evidence of congestion. Mean hematocrit changes were similar with and without persistent congestion (0.18 ± 3.4% and -0.19 ± 3.6%, respectively; P = .17). There was no correlation between the decline in congestion score and the change in hematocrit (P = .93). Hemoconcentration predicted lower mortality (hazard ratio 0.70, 95% confidence interval 0.54-0.90; P = .006). Persistent congestion was associated with increased mortality independent of hemoconcentration (Ptrend = .0003 for increasing levels of congestion score). CONCLUSIONS Hemoconcentration is weakly related to congestion as assessed clinically. Persistent congestion at discharge is associated with increased mortality regardless of hemoconcentration. Hemoconcentration is associated with better outcome but cannot substitute for clinically derived estimates of congestion to determine whether decongestion has been achieved.