QT prolongation is associated with increased mortality in end stage liver disease.

AIM: To determine the prevalence of QT prolongation in a large series of end stage liver disease (ESLD) patients and its association to clinical variables and mortality. METHODS: The QT interval was measured and corrected for heart rate for each patient, with a prolonged QT cutoff defined as QT > 450 ms for males and QT > 470 ms for females. Multiple clinical variables were evaluated including sex, age, serum sodium, international normalized ratio, creatinine, total bilirubin, beta-blocker use, Model for End-Stage Liver Disease (MELD), MELD-Na, and etiology of liver disease. RESULTS: Among 406 ESLD patients analyzed, 207 (51.0%) had QT prolongation. The only clinical variable associated with QT prolongation was male gender (OR = 3.04, 95%CI: 2.01-4.60, P < 0.001). During the study period, 187 patients (46.1%) died. QT prolongation was a significant independent predictor of mortality (OR = 1.69, 95%CI: 1.03-2.77, P = 0.039). In addition, mortality was also associated with viral etiology of ESLD, elevated MELD score and its components (P < 0.05 for all). No significant reversibility in the QT interval was seen after liver transplantation. CONCLUSION: QT prolongation was commonly encountered in an ESLD population, especially in males, and served as a strong independent marker for increased mortality in ESLD patients.

The Patient-Centered Discharge-An Electronic Discharge Process Is Associated With Improvements in Quality and Patient Satisfaction.

In this retrospective cohort study, 100 records were randomly selected from the intervention period (April 2012) and the control period (April 2011). The hospital's institutional database was queried to compare mortality, length of stay, and patient satisfaction, in the year prior to and the year after the integration of the new process. A chart review was performed to determine if the reengineered process was associated with an improvement in documentation. A scoring system was developed to gauge the quality and timeliness of the process. Institutional data regarding length of stay, mortality, patient satisfaction, and core measures compliance were compared for the pre- and postimplementation of the new process. The reengineered discharge process was associated with an improvement in patient satisfaction and in the quality of the discharge materials as measured by the "patient-centered transitions of care (PCTC) score." These improvements occurred without a significant increase in the time to complete a discharge.A redesigned discharge process resulted in system-wide improvements in the quality of information provided to the patient and their outpatient providers. This intervention was associated with an improvement in compliance with core measures, improvements in patient satisfaction and timeliness of discharge summary preparation.

Salivary Biomarkers, Oral Inflammation, and Functional Status in Patients With Heart Failure.

AIMS: To describe correlations and agreement between salivary and serum B-type natriuretic peptide (BNP), C-reactive protein (CRP), interleukin (IL)-6, and IL-10 and determine which biomarkers predict worse functional class in patients with heart failure (HF). METHODS: Serum and saliva were collected from 75 hospitalized patients with HF (57 ± 12 years, 43% female, New York Heart Association [NYHA] Classes I [4%], II [43%], and III [53%]). Oral inflammation was rated as good, fair, or poor. Spearman's ρ and Bland-Altman were used to determine correlations and agreement of the salivary and serum forms of each biomarker. Logistic regressions were used to determine which biomarkers predicted worse NYHA functional class, controlling for depression, body mass index, smoking, and oral inflammation. RESULTS: Median biomarker concentrations were as follows: BNP (serum 361 pg/ml, saliva 9 pg/ml), CRP (serum 13 ng/ml, saliva 25.6 ng/ml), IL-6 (serum 19.3 pg/ml, saliva 10.5 pg/ml), and IL-10 (serum 64.1 pg/ml, saliva 4.7 pg/ml). There was a moderate-to-strong correlation for serum-salivary CRP, weak correlation for serum-salivary IL-6, and no correlations for serum-salivary BNP and IL-10. The Bland-Altman test showed good salivary-serum agreement for all biomarkers, but as serum concentrations rose, salivary measures underestimated serum levels. Visible oral inflammation was the only predictor of worse NYHA class.

Early Prognosticators for Induction of Therapeutic Hypothermia Following Cardiac Arrest.

The American Heart Association recommends therapeutic hypothermia for comatose patients with return of spontaneous circulation after out-of-hospital ventricular fibrillation cardiac arrest. While there is a growing body of evidence for the general efficacy of therapeutic hypothermia, the individualized benefit of therapy is not currently predictable. Ninety-one consecutive patients, from April 2011 to July 2014, were treated at the University of Kentucky Medical Center with the therapeutic hypothermia protocol. Medical records were reviewed retrospectively. Data, such as preexisting comorbidities, cardiac arrest characteristics, and hospital course, were used to compose a multivariate logistic regression with mortality serving as the primary endpoint. The overall in-hospital mortality was 64% (n = 58) in this group. The arrest was considered cardiac etiology in 84% (n = 76) of patients, of which 49% (n = 45) were classed as ventricular fibrillation and 9% (n = 8) as ventricular tachycardia. The presence of a shockable rhythm, as well as shorter duration of cardiac arrest, was associated with increased survival, whereas time to target temperature was not. The presence of a preexisting neurologic disease was associated with a 10-fold increase in estimated odds of mortality. Age, serum lactate, ionized calcium, arterial pH, estimated glomerular filtration rate, and APACHE score were all predictors of mortality. Cardiac arrest is a devastating condition with a high mortality rate. Given the limited resources of the resuscitation community, the ability to predict survivors based on routinely obtained measures upon admission would be of tremendous value. In this study, we show a series of admission parameters that demonstrate predictive ability in identifying patients more likely to survive with therapeutic hypothermia.

The effect of rosuvastatin on thromboinflammation in the setting of acute coronary syndrome.

In patients with acute coronary syndromes (ACS), early therapy with high-dose statins may reduce short-term adverse clinical outcomes. The mechanisms responsible are not known but could involve anti-inflammatory or anti-thrombotic effects. Compelling evidence from experimental models and clinical studies suggests that the interplay between inflammatory and thrombotic systems, typified by platelet-monocyte and platelet-neutrophil interactions, might be a key regulator of ischemic vascular events. The study sought to determine if early, high-dose administration of the HMG-CoA reductase inhibitor rosuvastatin in the setting of ACS exerts beneficial vascular effects by reducing, and inhibiting biomarkers of thromboinflammation, such as platelet-monocyte and platelet-neutrophil interactions, and biomarkers of myocardial necrosis. A total of 54 patients presenting with ACS within 8 h of symptom onset were randomized to rosuvastatin 40 mg or placebo. Rosuvastatin significantly reduced interactions between platelets and circulating neutrophils (P = 0.015) and monocytes (P = 0.009) within 24 h. No significant effects were observed on platelet aggregation or plasma levels of PF4, sP-selectin, or sCD40L, whereas significant reductions of RANTES occurred over time in both treatment groups. Plasma levels of myeloperoxidase (MPO) declined more rapidly with rosuvastatin therapy than placebo. In a subset of patients with normal cardiac necrosis biomarkers at randomization, rosuvastatin therapy was associated with less myocardial damage as measured by troponin-I or CK-MB. Early administration of high-dose statin therapy in patients with ACS appears to improve biomarkers of inflammation within 8 h, which may translate into fewer ischemic events.

Biomarkers of acute myocardial infarction in the elderly: troponin and beyond.

In the broadest context, biological markers, or biomarkers, are molecules that characterize a biological system or process. In the setting of cardiovascular disease, a number of biomarkers have become an integral part of diagnostic and risk stratification strategies. In this review, we will discuss classic and emerging biomarkers of cardiovascular disease and the role of these biomarkers in the diagnosis and prognosis of elderly patients presenting with acute myocardial infarction.

QRS duration predicts death and hospitalization among patients with atrial fibrillation irrespective of heart failure: evidence from the AFFIRM study.

AIMS: The association of QRS duration (QRSd) with morbidity and mortality is understudied in patients with atrial fibrillation (AF). We sought to assess any association of prolonged QRS with increased risk of death or hospitalization among patients with AF. METHODS AND RESULTS: QRS duration was retrieved from the baseline electrocardiograms of patients enroled in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study and divided into three categories: <90, 90-119, ≥120 ms. Cox models were applied relating the hazards of mortality and hospitalizations to QRSd. Among 3804 patients with AF, 593 died and 2305 were hospitalized. Compared with those with QRS < 90 ms, patients with QRS ≥ 120 ms, had an increased mortality [hazard ratio (HR) 1.61, 95% confidence interval (CI): 1.29-2.03, P < 0.001] and hospitalizations (HR 1.14, 95% CI: 1.07-1.34, P = 0.043) over an average follow-up of 3.5 years. Importantly, for patients with QRS 90-119 ms, mortality and hospitalization were also increased (HR 1.31, P = 0.005 and 1.11, P = 0.026, respectively). In subgroup analysis based on heart failure (HF) status (previously documented or ejection fraction <40%), mortality was increased for QRS ≥ 120 ms patients with (HR 1.87, P < 0.001) and without HF (HR 1.63, P = 0.02). In the QRS 90-119 ms group, mortality was increased (HR 1.38, P = 0.03) for those with HF, but not significantly among those without HF (HR 1.23, P = 0.14). CONCLUSION: Among patients with AF, QRSd ≥ 120 ms was associated with a substantially increased risk for mortality (all-cause, cardiovascular, and arrhythmic) and hospitalization. Interestingly, an increased mortality was also observed among those with QRS 90-119 ms and concomitant HF.

Fibrinolytic therapy versus primary percutaneous coronary interventions for ST-segment elevation myocardial infarction in Kentucky: time to establish systems of care?

BACKGROUND: Fibrinolytic therapy is recommended for ST-segment myocardial infarctions (STEMI) when primary percutaneous coronary intervention (PPCI) is not available or cannot be performed in a timely manner. Despite this recommendation, patients often are transferred to PPCI centers with prolonged transfer times, leading to delayed reperfusion. Regional approaches have been developed with success and we sought to increase guideline compliance in Kentucky. METHODS: A total of 191 consecutive STEMI patients presented to the University of Kentucky (UK) Chandler Medical Center between July 1, 2009 and June 30, 2011. The primary outcome was in-hospital mortality and the secondary outcomes were major adverse cardiovascular events, extent of myocardial injury, bleeding, and 4) length of stay. Patients were analyzed by presenting facility-the UK hospital versus an outside hospital (OSH)-and treatment strategy (PPCI vs fibrinolytic therapy). Further analyses assessed primary and secondary outcomes by treatment strategy within transfer distance and compliance with American Heart Association guidelines. RESULTS: Patients presenting directly to the UK hospital had significantly shorter door-to-balloon times than those presenting to an OSH (83 vs 170 minutes; P < 0.001). This did not affect short-term mortality or secondary outcomes. By comparison, OSH patients treated with fibrinolytic therapy had a numeric reduction in mortality (4.0% vs 12.3%; P = 0.45). Overall, only 20% of OSH patients received timely reperfusion, 13% PPCI, and 42% fibrinolytics. In a multivariable model, delayed reperfusion significantly predicted major adverse cardiovascular events (odds ratio 3.87, 95% confidence interval 1.15-13.0; P = 0.02), whereas the presenting institution did not. CONCLUSIONS: In contemporary treatment of STEMI in Kentucky, ongoing delays to reperfusion therapy remain regardless of treatment strategy. For further improvement in care, acceptance of transfer delays is necessary and institutions should adopt standardized protocols in association with a regional system of care.

Increased mortality among patients taking digoxin--analysis from the AFFIRM study.

AIMS: Digoxin is frequently used for rate control of atrial fibrillation (AF). It has, however, been associated with increased mortality. It remains unclear whether digoxin itself is responsible for the increased mortality (toxic drug effect) or whether it is prescribed to sicker patients with inherently higher mortality due to comorbidities. The goal of our study was to determine the relationship between digoxin and mortality in patients with AF. METHODS AND RESULTS: The association between digoxin and mortality was assessed in patients enrolled in the AF Follow-Up Investigation of Rhythm Management (AFFIRM) trial using multivariate Cox proportional hazards models. Analyses were conducted in all patients and in subsets according to the presence or absence of heart failure (HF), as defined by a history of HF and/or an ejection fraction <40%. Digoxin was associated with an increase in all-cause mortality [estimated hazard ratio (EHR) 1.41, 95% confidence interval (CI) 1.19-1.67, P < 0.001], cardiovascular mortality (EHR 1.35, 95% CI 1.06-1.71, P = 0.016), and arrhythmic mortality (EHR 1.61, 95% CI 1.12-2.30, P = 0.009). The all-cause mortality was increased with digoxin in patients without or with HF (EHR 1.37, 95% CI 1.05-1.79, P = 0.019 and EHR 1.41, 95% CI 1.09-1.84, P = 0.010, respectively). There was no significant digoxin-gender interaction for all-cause (P = 0.70) or cardiovascular (P = 0.95) mortality. CONCLUSION: Digoxin was associated with a significant increase in all-cause mortality in patients with AF after correcting for clinical characteristics and comorbidities, regardless of gender or of the presence or absence of HF. These findings call into question the widespread use of digoxin in patients with AF.

Atomoxetine does not alter cocaine use in cocaine dependent individuals: double blind randomized trial.

BACKGROUND: Cocaine abuse continues to be a significant public health problem associated with morbidity and mortality. To date, no pharmacotherapeutic approach has proven effective for treating cocaine use disorders. Preclinical and clinical evidence suggests that noradrenergic activity may play a role in mediating some effects of cocaine and may be a rational target for treatment. METHODS: This double blind, placebo-controlled randomized, parallel group, 12-week outpatient clinical trial enrolled cocaine dependent individuals seeking treatment to examine the potential efficacy of the selective norepinephrine reuptake inhibitor, atomoxetine (80 mg/day; p.o.; n = 25), compared to placebo (n = 25). Subjects were initially stratified on cocaine use (< 15 days or ≥ 15 days of the last 30), age and race using urn randomization. Attendance, medication adherence and study compliance were reinforced with contingency management, and weekly counseling was offered. An array of measures (vital signs, laboratory chemistries, cognitive and psychomotor tests, cocaine craving and urine samples for drug testing) was collected throughout the study and at follow-up. RESULTS: Survival analysis revealed no differences in study retention between the two groups, with approximately 56% of subjects completing the 12-week study (Cox analysis χ(2) = .72; p = .40; Hazard Ratio 1.48 [95% CI 0.62-3.39]). GEE analysis of the proportion of urine samples positive for benzoylecgonine, a cocaine metabolite, revealed no differences between the atomoxetine and placebo groups (χ(2) = 0.2, p = .66; OR = 0.89 [95% CI 0.41-1.74]). Atomoxetine was generally well tolerated in this population. CONCLUSIONS: These data provide no support for the utility of atomoxetine in the treatment of cocaine dependence.

Salivary biomarkers associated with myocardial necrosis: results from an alcohol septal ablation model.

OBJECTIVE: To determine if salivary biomarkers demonstrate utility for identifying aspects of myocardial necrosis. METHODS: Twenty-one patients undergoing alcohol septal ablation (ASA) for treatment of hypertrophic cardiomyopathy provided serum and unstimulated whole saliva at baseline and incremental time points post-ASA. Samples were analyzed for seven biomarkers related to myocardial damage, inflammation, and tissue remodeling using immunosorbent assays. Levels were compared with baseline and levels observed in 97 healthy controls. RESULTS: Biomarkers of myocardial damage and inflammation (ie, troponin I, creatine kinase-MB, myoglobin, C-reactive protein) rose in serum 2- to 812-fold after ASA (P < .01). Significant elevations of 2.0- to 3.5-fold were observed with C-reactive protein and troponin I in saliva (P < .02). Significant correlations between levels in serum and saliva were observed for C-reactive protein, matrix metalloproteinase-9, and myeloperoxidase (P < .001). CONCLUSIONS: Select salivary biomarkers reflect changes that occur during, and subsequent to, myocardial necrosis caused by ASA.

Oral fluids that detect cardiovascular disease biomarkers.

OBJECTIVE: The aim of this study was to determine the utility of oral fluids for assessment of coronary and cardiovascular (CV) health. STUDY DESIGN: Twenty-nine patients with preexisting CV disease underwent an invasive cardiac procedure (alcohol septal ablation or percutaneous coronary intervention) and provided unstimulated whole saliva (UWS), sublingual swabs (LS), gingival swabs (GS) and serum at 0, 8, 16, 24, and 48 hours. Concentrations of 13 relevant biomarkers were determined and correlated with levels in serum and the oral fluids. RESULTS: Concentrations of the majority of biomarkers were higher in UWS than in LS and GS. Coronary and CV disease biomarkers in UWS correlated better with serum than with LS and GS based on group status and measures of time effect. Seven biomarkers demonstrated time effect changes consistent with serum biomarkers, including C-reactive protein and troponin I. CONCLUSIONS: Changes in serum biomarker profiles are reflected in oral fluids suggesting that oral fluid biomarkers could aid in the assessment of cardiac ischemia/necrosis.

Oral antiplatelet therapy for acute coronary syndromes: aspirin, P2Y12 inhibition and thrombin receptor antagonists.

The platelet is central to the pathophysiology of acute coronary syndromes (ACS) via its direct participation in the formation of the thrombotic occlusion and its participation in the coagulation cascade that results in the formation of thrombin. Antiplatelet therapy is a cornerstone of therapy in the setting of ACS. Unfortunately, many patients who receive intensive antiplatelet therapy remain at high risk for recurrent events. Current efforts to reduce this "residual risk" include lifestyle modifications, cardiac rehabilitation, and intensive therapy for dyslipidemia. Also being investigated are methods of individualizing and intensifying antiplatelet therapy. Novel compounds that promise to reduce recurrent ischemic events without an increase in bleeding events are being evaluated in clinical trials. This review summarizes ongoing efforts to improve the effectiveness of antiplatelet therapy among patients with ACS.

Plasma levels of sphingosine 1-phosphate are strongly correlated with haematocrit, but variably restored by red blood cell transfusions.

Anaemia and RBC (red blood cell) transfusion may be associated with worse clinical outcomes, especially with longer blood storage duration prior to transfusion. The mechanisms underlying these harmful effects are unknown. RBCs have been proposed to buffer plasma S1P (sphingosine 1-phosphate), a lysophospholipid essential for the maintenance of endothelial integrity and important in the regulation of haematopoietic cell trafficking. The present study examined the effect of anaemia, RBC transfusion and RBC storage duration on plasma S1P levels. Plasma S1P from 30 individuals demonstrated a linear correlation with Hct (haematocrit; R2 = 0.51, P < 0.001) with no evidence for a plateau at Hct values as low as 19%. RBC transfusion in 23 anaemic patients with baseline mean Hct of 22.2 ± 0.34% (value is the mean ± S.D.) increased Hct to 28.3 ± 0.6% at 72 h. Despite an Hct increase, RBC transfusion failed to elevate plasma S1P consistently. A trend towards an inverse correlation was observed between RBC storage duration and the post-transfusion increase in plasma S1P. After 30 days of storage, RBC S1P decreased to 19% of that observed in fresh (3-7-day-old) RBC segments. RBC membranes contain low levels of both S1P phosphatase and S1P lyase activities that may account for the decline in S1P levels with storage. Our results support a role for RBCs in buffering plasma S1P and identify a disturbance in the capacity after transfusion. Changes in S1P content may contribute to an RBC storage lesion. Further studies should investigate the clinical significance of alterations in circulating S1P levels and the potential value of enriching stored RBCs with S1P.