Treatment of heart failure with preserved ejection fraction

Heart failure contributes to more than 1 million hospitalizations annually and is one of the most common causes of repeat hospitalizations in the elderly. Previously, it was thought that mortality from heart failure with preserved ejection fraction (PEF) was lower than that from heart failure with reduced ejection fraction (REF), but more recent data infer similar mortality. Although the mortality rate in patients with heart failure with REF is decreasing, the mortality rate in patients with heart failure with PEF remains unchanged--possibly due to the lack of evidence-based treatment regimens or greater recognition of the disease. Without sufficient trials in patients with heart failure with PEF, clinicians are forced to extrapolate treatment from data proven to benefit patients with heart failure with REF. There is no question that clinical trials including only patients with heart failure with PEF are limited. In addition, the definition and clinical diagnosis of this syndrome are not clearly defined, and the guidelines available for treatment lack specificity in recommendations. To describe the current literature for the treatment of heart failure with PEF, we conducted a MEDLINE search of the English-language literature (1950-2009) to identify studies that pertain to the treatment of patients with heart failure with PEF. Ongoing clinical trials continue, but until data become available, clinicians must base their treatment strategies for heart failure with PEF on sparse information.     

Chlorthalidone reduces cardiovascular events compared with hydrochlorothiazide: a retrospective cohort analysis

There is significant controversy around whether chlorthalidone (CTD) is superior to hydrochlorothiazide (HCTZ) in hypertension management. The objective of this analysis was to evaluate the effects of CTD compared with HCTZ on cardiovascular event (CVE) rates. We performed a retrospective observational cohort study from the Multiple Risk Factor Intervention Trial data set from the National Heart, Lung, and Blood Institute. The Multiple Risk Factor Intervention Trial was a cardiovascular primary prevention trial where participants were men 35 to 57 years of age enrolled and followed beginning in 1973. CVEs were measured yearly, and time to event was assessed by Cox regression. Systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, potassium, glucose, and uric acid were measured yearly. The difference between groups was evaluated by repeated-measures mixed modeling, and each model was adjusted for predictors of each variable. CVEs were significantly lower in those on CTD (adjusted hazard ratio: 0.51 [95% CI: 0.43 to 0.61]; P<0.0001) and on HCTZ (adjusted hazard ratio: 0.65 [95% CI: 0.55 to 0.75]; P<0.0001) compared with those who took neither drug. When comparing the 2 drugs, CTD had significantly fewer CVEs compared with HCTZ (P=0.0016). CTD displayed significantly lower SBP (P<0.0001), lower total cholesterol (P<0.0001), lower low-density lipoprotein cholesterol (P=0.0009), lower potassium (P=0.0003), and higher uric acid (P<0.0001) over time compared with HCTZ. In conclusion, both HCTZ and CTD reduce CVEs compared with neither drug. When comparing both drugs, CTD reduces CVEs more than HCTZ, suggesting that CTD may be the preferred thiazide-type diuretic for hypertension in patients at high risk of CVEs.     

Direct cerebral oxygenation monitoring--a systematic review of recent publications

This review has been compiled to assess publications related to the clinical application of direct cerebral tissue oxygenation (PtiO2) monitoring published in international, peer-reviewed scientific journals. Its goal was to extract relevant, i.e. positive and negative information on indications, clinical application, safety issues and impact on clinical situations as well as treatment strategies in neurosurgery, neurosurgical anaesthesiology, neurosurgical intensive care, neurology and related specialties. For completeness' sake it also presents some related basic science research. PtiO2 monitoring technology is a safe and valuable cerebral monitoring device in neurocritical care. Although a randomized outcome study is not available its clinical utility has repeatedly been clearly confirmed because it adds a monitoring parameter, independent from established cerebral monitoring devices. It offers new insights into cerebral physiology and pathophysiology. Pathologic values have been established in peer-reviewed research, which are not only relevant to outcome but are treatable. The benefits clearly outweigh the risks, which remains unchallenged in all publications retrieved. It is particularly attractive because it offers continuous, real-time data and is available at the bedside.     

Diffusion tensor imaging in acquired blind humans

Prion diseases, also called transmissible spongiform encephalopathies (TSEs), are fatal neurodegenerative disorders characterized by neuronal loss, astrogliosis, and spongiform changes in the brain. It is postulated that appearance of astrogliosis may provide the neurotrophic factors to prevent or reduce neuronal cell loss in the pathogenesis of prion diseases. To investigate the role of the glial cell line-derived neurotrophic factor (GDNF), we studied the expression levels of GDNF mRNA and protein in an animal model of prion diseases. The expression levels of GDNF mRNA and protein were significantly increased in the brains of scrapie-infected mice at 100 and 160 days after inoculation with scrapie strain compared with those of control mice. In addition, we found more intensive immunoreactivity of GDNF in the brains of scrapie-infected mice, specifically in the hippocampal astrocytes, than was seen in control mice. These results suggest that GDNF participates in protection against neuronal cell loss and atrophy in neurodegenerative disorders, which may play one of the important roles in the pathogenic mechanisms of prion diseases.     

Aberrant expression of retinoic acid signaling molecules influences patient survival in astrocytic gliomas

Undifferentiated cell populations may influence tumor growth in malignant glioma. We investigated potential disruptions in the retinoic acid (RA) differentiation pathway that could lead to a loss of differentiation capacity, influencing patient prognosis. Expression of key molecules belonging to the RA differentiation pathway was analyzed in 283 astrocytic gliomas and was correlated with tumor proliferation, tumor differentiation, and patient survival. In addition, in situ concentrations of retinoids were measured in tumors, and RA signaling events were studied in vitro. Unlike other tumors, in gliomas expression of most RA signaling molecules increased with malignancy and was associated with augmented intratumoral retinoid levels in high-grade gliomas. Aberrantly expressed RA signaling molecules included i) the retinol-binding protein CRBP1, which facilitates cellular retinoid uptake; ii) ALDH1A1, capable of activating RA precursors; iii) the RA-degrading enzyme CYP26B1; and iv) the RA-binding protein FABP5, which can inhibit RA-induced differentiation. In contrast, expression of the RA-binding protein CRABP2, which fosters differentiation, was decreased in high-grade tumors. Moreover, expression of CRBP1 correlated with tumor proliferation, and FABP5 expression correlated with an undifferentiated tumor phenotype. CRBP1 and ALDH1A1 were independent prognostic markers for adverse patient survival. Our data indicate a complex and clinically relevant deregulation of RA signaling, which seems to be a central event in glioma pathogenesis.     

Primary percutaneous coronary intervention for acute ST elevation myocardial infarction--first year's experience of a tertiary referral centre in the UK

This study evaluated the first year's experience of a large interventional centre in the UK after a primary percutaneous coronary intervention (PCI) programme that runs 24 hours a day and seven days a week was started. Workload, patient outcome, length of stay, and effect on the remainder of the interventional service were analysed. The primary PCI service for a mainly urban population of 800,000 was started in April 2005. All relevant characteristics, details of procedures, outcome, and other data on quality of care were collected and entered prospectively onto a computerised database. Data were analysed with SPSS (version 13.0). Over a 12-month period, 305 patients were diagnosed with ST elevation myocardial infarction (STEMI), of whom 259 (85%) were accepted for primary PCI. Median door-to-balloon time was 98 minutes, which decreased from 106 minutes in the first six months to 93 minutes in the second six months (p < 0.005). In-hospital mortality was 4.5% and 30-day mortality was 4.9%. Median length of stay was three days, which was reduced from the six days previously reported after thrombolysis. Waiting times for other acute and elective PCI procedures did not increase after initiation of the primary PCI programme. Primary PCI can be delivered successfully in a setting in the UK with low mortality and reduced length of stay and without a negative impact on other interventional services.     

External validation, extension and recalibration of Braunwald's simple risk index in a community-based cohort of patients with both STEMI and NSTEMI

BACKGROUND: Using the simple risk index (SRI) that is based on age, heart rate and systolic blood pressure, we sought to evaluate the ability to predict outcome in AMI patients in a community-based population. METHODS AND RESULTS: We identified and evaluated 3684 consecutive patients with an admission diagnosis of possible AMI, who attended between 1st September and 30th November 1995. Two thousand one hundred fifty three patients had confirmed evidence of WHO definition AMI, of whom 1656 survived to hospital discharge. We evaluated the ability of the SRI to predict mortality over 30 days using the score generated by the equation (heart ratex[age/10]2)/systolic blood pressure. The SRI was a strong (c-statistic = 0.77 CI 0.74-0.79) predictor of 30-day mortality in both STEMI and all consecutive cases of WHO definition AMI. However, the model showed poor calibration when used on a community-based population with 30-day mortality being underestimated across all risk quintiles. Consequently we sought to recalibrate the quantitative aspects of the model for the total AMI population in the following way (Risk Index; 30-day mortality) (< or = 29.2; 9.2%), (29.3-37.8; 23.9%), (37.9-47.3; 34.6%), (47.4-61.5; 40.3%), (> or = 61.6; 65.5%). CONCLUSION: We have externally validated the SRI in an unselected cohort of consecutive WHO definition AMI patients. However, the original model consistently underestimated the likelihood of death at 30 days regardless of the calculated risk score. We have therefore suggested corrections to the risk estimates, to allow its application in an unselected community cohort.     

Trauma and grief 2–7 years after termination of pregnancy because of fetal anomalies – a pilot study

The aim of the study was to obtain information on the long-term posttraumatic stress response and grief several years after termination of pregnancy due to fetal malformation. We investigated 83 women who had undergone termination of pregnancy between 1995 and 1999 and compared them with 60 women 14 days after termination of pregnancy and 65 women after the spontaneous delivery of a full-term healthy child. Women 2–7 years after termination of pregnancy were expected to show a significantly lower degree of traumatic experience and grief than women 14 days after termination of pregnancy. Contrary to the hypothesis, however, the results showed no significant intergroup differences with respect to the degree of traumatic experience. With the exception of one subscale (fear of loss), this also applied to the grief reported by the women. However, both groups differed significantly in their posttraumatic stress response from women who had given spontaneous birth to a full-term healthy child. The results indicate that termination of pregnancy is to be seen as an emotionally traumatic major life event which leads to severe posttraumatic stress response and intense grief reactions that are still detectable some years later.