Trastuzumab prolongs survival in patients with human epidermal growth factor receptor type 2-positive breast cancer. Sequential left ventricular (LV) ejection fraction (EF) assessment has been mandated to detect myocardial dysfunction because of the risk of heart failure with this treatment. Myocardial deformation imaging is a sensitive means of detecting LV dysfunction, but this technique has not been evaluated in patients treated with trastuzumab.

The aim of this study was to investigate whether changes in tissue deformation, assessed by myocardial strain and strain rate (SR), are able to identify LV dysfunction earlier than conventional echocardiographic measures in patients treated with trastuzumab.

METHODS:
Sequential echocardiograms (n = 152) were performed in 35 female patients (51 +/- 8 years) undergoing trastuzumab therapy for human epidermal growth factor receptor type 2-positive breast cancer.

Left ventricular EF was measured by 2- and 3-dimensional (2D and 3D) echocardiography, and myocardial deformation was assessed using tissue Doppler imaging and 2D-based (speckle-tracking) strain and SR. Change over time was compared every 3 months between baseline and 12 months.

RESULTS:
There was no overall change in 3D-EF, 2D-EF, myocardial E-velocity, or strain. However, there were significant reductions seen in tissue Doppler imaging SR (P < .05), 2D-SR (P < .001), and 2D radial SR (P < .001). A drop > or =1 SD in 2D longitudinal SR was seen in 18 (51%) patients; 13 (37%) had a similar drop in radial SR. Of the 18 patients with reduced longitudinal SR, 3 had a concurrent reduction in EF > or =10%, and another 2 showed a reduction over 20 months follow-up.

CONCLUSIONS:
Myocardial deformation identifies preclinical myocardial dysfunction earlier than conventional measures in women undergoing treatment with trastuzumab for breast cancer.


"Use of myocardial deformation imaging to detect preclinical myocardial dysfunction before conventional measures in patients undergoing breast cancer treatment with trastuzumab."
Am Heart J. 2009 Aug; 158(2): 294-301Hare JL, Brown JK, Leano R, Jenkins C, Woodward N, Marwick

This observational study used repeated measures over 24 hr to investigate ambulatory blood pressure (BP) and physical activity (PA) profiles in community-based individuals with heart failure (HF).

The aims were to (a) compare BP dipping and PA between two groups of HF patients with different functional statuses, and (b) determine whether the strength of the association between ambulatory BP and PA varies by functional status in Heart Failure.

Ambulatory BP was measured every 30 min with a SpaceLabs 90207; a Basic Motionlogger actigraph was used to measure PA minute-by-minute. Fifty-six participants (54% female, age 66.96 +/- 12.35 years) completed data collection. Functional status was based on New York Heart Association (NYHA) ratings.

Twenty-seven patients had no limitation of PA (NYHA Class I HF), whereas 29 had some limitation of PA but no discomfort at rest (NYHA Class II or III HF). Patients with Class I Heart Failure had a significantly greater degree of BP dipping than those with Class II/III HF after controlling for left ventricular ejection fraction.

In a mixed-model analysis, PA was significantly related to ambulatory systolic and diastolic BP and mean arterial pressure. The strength of the association between PA and BP was not significantly different for the two groups of patients.

These findings demonstrate differences between Class I and Class II/II HF in BP dipping status and ambulatory BP but not PA. Longitudinal research is recommended to improve understanding of the influence of disease progression on changes in 24-hr PA and BP profiles of patients with Heart Failure.


Ambulatory Blood Pressure and Physical Activity in Heart Failure
Biol Res Nurs. 2009 Jul 17; Tai MK, Meininger J, Frazier L, Chan W (Hubmed)


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J Gen Physiol. 2009 Jul 13; Brunet S, Scheuer T, Catterall WAL-type Ca(2+) currents conducted by Ca(v)1.2 channels initiate excitation-contraction coupling in cardiac myocytes. Intracellular Mg(2+) (Mg(i)) inhibits the ionic current of Ca(v)1.2 channels. Because Mg(i) is altered in ischemia and heart failure, its regulation of Ca(v)1.2 channels is important in understanding cardiac pathophysiology. Here, we studied the effects of Mg(i) on voltage-dependent inactivation (VDI) of Ca(v)1.2 channels using Na(+) as permeant ion to eliminate the effects of permeant divalent cations that engage the Ca(2+)-dependent inactivation process. We confirmed that increased Mg(i) reduces peak ionic currents and increases VDI of Ca(v)1.2 channels in ventricular myocytes and in transfected cells when measured with Na(+) as permeant ion. The increased rate and extent of VDI caused by increased Mg(i) were substantially reduced by mutations of a cation-binding residue in the proximal C-terminal EF-hand, consistent with the conclusion that both reduction of peak currents and enhancement of VDI result from the binding of Mg(i) to the EF-hand (K(D) approximately 0.9 mM) near the resting level of Mg(i) in ventricular myocytes. VDI was more rapid for L-type Ca(2+) currents in ventricular myocytes than for Ca(v)1.2 channels in transfected cells. Coexpression of Ca(v)beta(2b) subunits and formation of an autoinhibitory complex of truncated Ca(v)1.2 channels with noncovalently bound distal C-terminal domain (DCT) both increased VDI in transfected cells, indicating that the subunit structure of the Ca(v)1.2 channel greatly influences its VDI. The effects of noncovalently bound DCT on peak current amplitude and VDI required Mg(i) binding to the proximal C-terminal EF-hand and were prevented by mutations of a key divalent cation-binding amino acid residue. Our results demonstrate cooperative regulation of peak current amplitude and VDI of Ca(v)1.2 channels by Mg(i), the proximal C-terminal EF-hand, and the DCT, and suggest that conformational changes that regulate VDI are propagated from the DCT through the proximal C-terminal EF-hand to the channel-gating mechanism.

Medicine (Baltimore). 2009 Jul; 88(4): 236-43Neumann T, Manger B, Schmid M, Kroegel C, Hansch A, Kaiser WA, Reinhardt D, Wolf G, Hein G, Mall G, Schett G, Zwerina JCardiac disease is a major contributor to disease-related death in Churg-Strauss syndrome (CSS). We conducted the current study to determine the prevalence and clinical impact of cardiac involvement in CSS patients. We performed a multicenter, cross-sectional analysis of patients diagnosed with CSS. Cardiac workup included electrocardiography, echocardiography, cardiac magnetic resonance imaging (MRI), and endomyocardial biopsy.We analyzed 49 patients with CSS: 22 patients had clinical evidence of cardiac involvement. A negative antineutrophil cytoplasmic antibodies (ANCA) test and much higher eosinophil counts (9947 vs. 3657/microL, respectively, p < 0.001) distinguished patients with cardiac involvement from those without. Impaired left ventricular function (50%), mild to severe valvular insufficiencies (73%), and pericardial effusions (41%) were common findings in these patients. Endomyocarditis was found in 13 patients (59%) as detected by cardiac MRI, cardiac thrombus formation, and endomyocardial biopsy, and was associated with impaired cardiac function. After a mean follow-up of 47 months, most patients had regained or maintained good cardiac function. However, patients with endomyocarditis had a more severe outcome. Two patients died (61 and 99 mo after diagnosis, respectively), both due to severe cardiomyopathy and heart failure.Cardiac involvement is common in patients with CSS and is associated with the absence of ANCA and high eosinophil counts. Endomyocarditis may represent the most severe manifestation eventually causing fatal outcome. A structured clinical assessment incorporating cardiac imaging with echocardiography and MRI can identify impaired cardiac function and endomyocardial abnormalities.

Exp Physiol. 2009 Jul 10; Boyett MThe Cardiac Conduction System (CCS), consisting of the sinoatrial node, atrioventricular node and His-Purkinje system, is responsible for the initiation and coordination of the heart beat. In the last decade, our understanding of the CCS has been transformed. Immunohistochemistry used in conjunction with anatomical techniques has transformed our understanding of its anatomy: arguably, we now understand the position of the sinoatrial node (not the same as in medical textbooks) and our new understanding of the atrioventricular node anatomy means that we can compute its physiological and pathophysiological behaviour. Ion channel expression in the CCS has been shown to be fundamentally different to that in the working myocardium. Dysfunction of the CCS has previously been attributed to fibrosis, but it is now clear that remodelling of ion channels plays an important role in dysfunction during ageing, heart failure and atrial fibrillation. Differences in ion channel expression may even be responsible for the bradycardia in the athlete and differences in heart rate among different species (such as human and mouse). Recent work has highlighted less well known components of the CCS, including tricuspid, mitral and aortic rings and even a third (retroaortic) node. These additional tissues do not participate in the initiation and coordination of the heart beat and instead they are likely to be the source of various life-threatening arrhythmias. During embryological development, all parts of the CCS have been shown to develop from the primary myocardium of the linear heart tube partly under the action of the transcription factor, Tbx3.

Am J Physiol Lung Cell Mol Physiol. 2009 Jul 10; Maron MB, Luther DJ, Pilati CF, Ohanyan V, Li T, Koshy S, Horne WI, Meszaros JG, Walro JM, Folkesson HGThe alveolar epithelium plays a critical role in resolving pulmonary edema. We thus hypothesized that its function might be upregulated in rats with heart failure, a condition that severely challenges the lungs' ability to maintain fluid balance. Heart failure was induced by left coronary artery ligation. Echocardiographic and cardiovascular hemodynamics confirmed its development at 16 weeks post-ligation. At that time, alveolar fluid clearance was measured by an increase in protein concentration over 1 h of a 5% albumin solution instilled into the lungs. Baseline alveolar fluid clearance was similar in heart failure and age-matched control rats. Terbutaline was added to the instillate to determine whether heart failure rats responded to beta-adrenoceptor stimulation. Alveolar fluid clearance in heart failure rats was increased by 194% after terbutaline stimulation compared to 153% increase by terbutaline in control rats. To determine the mechanisms responsible for this accelerated alveolar fluid clearance, we measured ion transporter expression (ENaC, Na,K-ATPase, CFTR). No significant upregulation was observed for these ion transporters in the heart failure rats. Lung morphology showed significant alveolar epithelial type II cell hyperplasia in heart failure rats. Thus, alveolar epithelial type II cell hyperplasia is the likely explanation for the increased terbutaline-stimulated alveolar fluid clearance in heart failure rats. These data provide evidence for previously unrecognized mechanisms that can protect against or hasten resolution of alveolar edema in heart failure. Key words: ENaC, ATII cell hyperplasia, alveolar epithelium, pulmonary edema.

Epidemiology. 2009 Jul 10; Lin S, Luo M, Walker RJ, Liu X, Hwang SA, Chinery RBACKGROUND:: Although the association of high temperatures with mortality is well-documented, the association with morbidity has seldom been examined. We assessed the potential impact of hot weather on hospital admissions due to cardiovascular and respiratory diseases in New York City. We also explored whether the weather-disease relationship varies with socio-demographic variables. METHOD:: We investigated effects of temperature and humidity on health by linking the daily cardiovascular and respiratory hospitalization counts with meteorologic conditions during summer, 1991-2004.We used daily mean temperature, mean apparent temperature, and 3-day moving average of apparent temperature as the exposure indicators. Threshold effects for health risks of meteorologic conditions were assessed by log-linear threshold models, after controlling for ozone, day of week, holidays, and long-term trend. Stratified analyses were used to evaluate temperature-demographic interactions. RESULTS:: For all 3 exposure indicators, each degree C above the threshold of the temperature-health effect curve (29 degrees C-36 degrees C) was associated with a 2.7%-3.1% increase in same-day hospitalizations due to respiratory diseases, and an increase of 1.4%-3.6% in lagged hospitalizations due to cardiovascular diseases. These increases for respiratory admissions were greater for Hispanic persons (6.1%/ degrees C) and the elderly (4.7%/ degrees C). At high temperatures, admission rates increased for chronic airway obstruction, asthma, ischemic heart disease, and cardiac dysrhythmias, but decreased for hypertension and heart failure. CONCLUSIONS:: Extreme high temperature appears to increase hospital admissions for cardiovascular and respiratory disorders in New York City. Elderly and Hispanic residents may be particularly vulnerable to the temperature effects on respiratory illnesses.

Am J Physiol Heart Circ Physiol. 2009 Jul 10; Parrish DC, Alston EN, Rohrer H, Hermes SM, Aicher SA, Nkadi P, Woodward WR, Stubbusch J, Gardner RT, Habecker BAInflammatory cytokines that act through gp130 are elevated in the heart after myocardial infarction and in heart failure. These cytokines are potent regulators of neurotransmitter and neuropeptide production in sympathetic neurons, but are also important for the survival of cardiac myocytes following damage to the heart. To examine the effect of gp130 cytokines on cardiac nerves we used gp130(DBH-Cre/lox) mice, which have a selective deletion of the gp130 cytokine receptor in neurons expressing dopamine beta hydroxylase (DBH). Basal sympathetic parameters including norepinephrine (NE) content, tyrosine hydroxylase expression, NE transporter expression, and sympathetic innervation density appeared normal in gp130(DBH-Cre/lox) compared to wild type mice. Likewise, basal cardiovascular parameters measured under isoflurane anesthesia were similar in both genotypes including mean arterial pressure, left ventricular peak systolic pressure, dP/dtMAX and dP/dtMIN. However, pharmacological interventions revealed autonomic imbalance in gp130(DBH-Cre/lox) mice that was correlated with increased incidence of premature ventricular complexes after reperfusion. Stimulation of NE release with tyramine and infusion of the beta agonist dobutamine revealed blunted adrenergic transmission that correlated with decreased beta receptor expression in gp130(DBH-Cre/lox) hearts. Due to the developmental expression of the DBH-Cre transgene in parasympathetic ganglia, gp130 was eliminated. Cholinergic transmission was impaired in gp130(DBH-Cre/lox) hearts due to decreased parasympathetic drive, but tyrosine hydroxylase immunohistochemistry in the brainstem revealed that catecholaminergic nuclei appeared grossly normal. Thus, apparently normal basal parameters in gp130(DBH-Cre/lox) mice mask autonomic imbalance that includes alterations in sympathetic and parasympathetic transmission. Key words: cardiac, sympathetic, parasympathetic, ischemia-reperfusion.

Stroke. 2009 Jul 9; Putaala J, Curtze S, Hiltunen S, Tolppanen H, Kaste M, Tatlisumak TBACKGROUND AND PURPOSE: Data on mortality and its prognostic factors after an acute ischemic stroke in young adults are scarce and based on relatively small heterogeneous patient series. METHODS: We analyzed 5-year mortality data of all consecutive patients aged 15 to 49 with first-ever ischemic stroke treated at the Department of Neurology, Helsinki University Central Hospital, from January 1994 to September 2003. We followed up the patients using data from the mortality registry of Statistics Finland. We used life table analyses for calculating mortality risks. Kaplan-Meier method allowed comparisons of survival between clinical subgroups. We used the Cox proportional hazard model for identifying predictors of mortality. Stroke severity was measured using the National Institutes of Health Stroke Scale and the Glasgow Coma Scale. RESULTS: Among the 731 patients (mean age, 41.5+/-7.4 years; 62.8% males) followed, 78 died. Cumulative mortality risks were 2.7% (95% CI, 1.5% to 3.9%) at 1 month, 4.7% (3.1% to 6.3%) at 1 year, and 10.7% (9.9% to 11.5%) at 5 years with no gender difference. Those >/=45 years of age had lower probabilities of survival. Among the 30-day survivors (n=711), stroke caused 21%, cardioaortic and other vascular causes 36%, malignancies 12%, and infections 9% of the deaths. Malignancy, heart failure, heavy drinking, preceding infection, type 1 diabetes, increasing age, and large artery atherosclerosis causing the index stroke independently predicted 5-year mortality adjusted for age, gender, relevant risk factors, stroke severity, and etiologic subtype. CONCLUSIONS: Despite the overall low mortality after an ischemic stroke in young adults, several recognizable subgroups had substantially increased risk of death in the long term.

Eur J Cardiothorac Surg. 2009 Jul 7; Westaby S, Siegenthaler M, Beyersdorf F, Masseti M, Pepper J, Khayat A, Hetzer R, Frazier OHObjective: We tested the hypothesis that a miniaturised axial flow pump with infection-resistant power delivery could improve longevity and quality of life (QOL) in advanced heart failure patients deemed unsuitable for transplantation. Methods: The study included all non-United States Jarvik 2000 patients (n=46), where a skull-pedestal-based power line was employed with the intention of long-term support. Patient age ranged from 29 to 80 years. Of the 46 patients, 42 were male. All were New York Heart Association (NYHA) IV predominantly with idiopathic dilated (n=22) or ischaemic (n=18) cardiomyopathy. The experience (2000-2008) included the learning curve of 10 centres. Results: The internal components are imperceptible. The power/control system is user friendly, allowing excellent QOL. There has been no pump malfunction. The Kaplan-Meier survival analysis is shown. The longest event-free survival is 7.5 years. Support exceeded 3 years in five cases. The cumulative experience exceeds 50 years. Three patients were transplanted, and two pumps were replaced at 90 and 203 days. Nineteen cases are ongoing (mean: 663 days), while 22 died during support (mean survival: 402 days), of which five from non-device-related diseases. Temporary local infection occurred in three pedestals, and there has been no pump infection. Incidence of thrombo-embolic events showed wide variation between centres. Conclusions: From this learning-curve experience, both left ventricular assist device (LVAD) and power delivery are reliable and promising for destination therapy. Early mortality is similar to other studies and relates to the severity of illness. Pump infection has not occurred and prolonged event-free survival is clearly possible with expert medical management.

J Am Coll Cardiol. 2009 Jul 14; 54(3): 234-41Sorajja P, Nishimura RA, Gersh BJ, Dearani JA, Hodge DO, Wiste HJ, Ommen SROBJECTIVES: The purpose of this study was to characterize the prognosis of minimally symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM). BACKGROUND: Recent data have suggested that obstruction may be present in the majority of HCM patients, irrespective of cardiac symptoms. The prognosis of minimally symptomatic obstructive HCM remains poorly defined. METHODS: We examined 544 consecutive adult patients (age 59 +/- 16 years; 55% men) with obstructive HCM documented by Doppler echocardiography who were free of severe cardiac symptoms, and we performed clinical follow-up (median 9.3 years). RESULTS: There was only a slight excess mortality of the cohort in comparison to the expected survival of a similar U.S. general population (10-year observed vs. expected survival, 69.3% vs. 71.9%; p = 0.04) and 46% of the deaths were attributable to noncardiac causes. However, there was a clear relation between increasing severity of the left ventricular outflow tract (LVOT) gradient and outcome. For patients with high resting gradients (Doppler peak velocity >4 m/s), survival was significantly impaired (53% at 10 years; p = 0.001 vs. expected), and death or severe symptoms occurred in 68% of these patients within 10 years after the initial evaluation. Conversely, there was no impairment of long-term survival for patients with less-severe resting obstruction. Independent predictors of mortality in the entire cohort were age, prior stroke, and LVOT gradient severity. CONCLUSIONS: Patients with obstructive HCM and mild or no symptoms have only slight excess mortality. However, patients with markedly elevated resting LVOT gradients are at a high risk of heart failure and death. These findings may have important implications for therapy, including the timing of septal reduction therapy.

Eur Heart J. 2009 Jul 8; Sinnaeve PR, Ezekowitz JA, Bogaerts K, Droogne W, Jarai R, Huber K, Granger CB, Desmet WJ, Armstrong PW, Van de Werf FJ, Aims N-terminal pro-brain natriuretic peptide (NT-proBNP) levels predict outcomes in ST-elevation myocardial infarction patients treated with fibrinolysis or primary percutaneous coronary intervention (PCI). However, its role in facilitated PCI has not yet been assessed; it may be a tool to evaluate the lower event rates with primary PCI in ASSENT-4. Methods and results In ASSENT-4, 1667 patients were randomized to tenecteplase (TNK) followed by PCI or primary PCI alone. Baseline, discharge/Day 7, and 90-day NT-proBNP levels were available for 1008, 971, and 813 patients. Increasing quartiles of baseline NT-proBNP levels were associated with a higher risk of the combined endpoint of death, heart failure, and shock at 90 days and 1-year mortality (P < 0.001). Events were more common with TNK + PCI, regardless of baseline NT-proBNP quartile. When analysing baseline NT-proBNP as a continuous variable, no treatment interaction was observed for the primary endpoint (P = 0.17) or 1-year mortality (P = 0.08). Overall, NT-proBNP levels at Day 7 or 90 were not different between the two treatments. In patients with TIMI 2-3 flow before PCI, NT-proBNP at Day 90 was lower in PCI-only patients (P = 0.01), although no interaction was observed (P = 0.14). In TNK-pre-treated patients without reperfusion (TIMI 0-1) after PCI, NT-proBNP levels at Day 7 or 90 were not significantly higher than in PCI patients. Conclusion Baseline NT-proBNP predicts outcome at 90 days and 1 year in patients undergoing PCI with or without facilitation with TNK. A higher rate of reperfusion in lytic-pre-treated patients did not result in lower NT-proBNP during follow-up. Thus, baseline and subsequent NT-proBNP levels do not explain the lower mortality rate with PCI alone seen in this trial.

J Clin Apher. 2009 Jul 9; Doesch AO, Konstandin M, Celik S, Kristen A, Frankenstein L, Hardt S, Goeser S, Kaya Z, Katus HA, Dengler TJOBJECTIVES:: The objective of this study was to investigate functional effects of immunoadsorption (IA) in severely limited study patients with chronic nonfamilial dilated cardiomyopathy (DCM), and to analyze the prevalence of Troponin I (TNI) autoantibodies. BACKGROUND:: Immunoadsorption (IA) has been shown to induce early hemodynamic improvement in patients with nonfamilial DCM. METHODS:: We performed IA using Immunosorba columns on five consecutive days in 27 patients with chronic DCM, congestive heart failure of NYHA class >/=II, left ventricular ejection fraction below 40%, and mean time since initial diagnosis of 7.2 +/- 6.8 years. RESULTS:: Immediately after IA, IgG decreased by 87.7% and IgG3 by 58.5%. Median NT-pro BNP was reduced from 1740.0 ng/L at baseline to 1504.0 ng/L after 6 months (P = 0.004). Mean left ventricular ejection fraction (LVEF) was not significantly improved overall (24.1 +/- 7.8% to 25.4 +/- 10.4% after 6 months, P = 0.38), but LVEF improved >/=5% (absolute) in 9 of 27 (33%) patients. Bicycle spiroergometry showed a significant increase in exercise capacity from 73.7 +/- 29.4 Watts to 88.8 +/- 31.1 Watts (P = 0.003) after 6 months while VO2max rose from 13.7 +/- 3.8 to 14.9 +/- 3.0 mL/min kg after 6 months (P = 0.09). Subgroup analysis revealed a higher NT-pro BNP reduction in patients with shorter disease duration (P = 0.03) and without TNI autoantibodies at baseline (P = 0.05). All 9 patients with an absolute increase of LVEF of >/=5.0% were diabetic (P = 0.0001). CONCLUSIONS:: In this study, on severely limited heart failure patients with nonfamilial DCM, IA therapy moderately improved markers of heart failure severity in a limited subgroup of patients. This may be due to the selected study population with end-stage heart failure patients and the lower reduction of IgG3 compared to previous studies. Future blinded multicenter studies are necessary to identify those patients that benefit most. J. Clin. Apheresis 2009. (c) 2009 Wiley-Liss, Inc.

Ultrasound Obstet Gynecol. 2009 Jul 8; Ghosh GS, Fu J, Olofsson P, Gudmundsson SOBJECTIVES: Under physiological conditions the blood flow velocity waveform in the umbilical vein (UV) has an even non-pulsating pattern. Pulsations in the UV have been described in human fetuses exposed to chronic hypoxia and heart failure. Current techniques for fetal surveillance during labor and delivery involve a risk of both over- and underestimation of fetal hypoxia. We aimed to examine whether pulsations in the UV appear in the human fetus during suspected intrapartum hypoxia, and if so whether they are associated with increased risk of operative delivery for fetal distress (ODFD). METHODS: This was a prospective double blind study including 52 normal pregnancies. A Doppler examination of the UV was performed on 26 fetuses with pathological and 26 fetuses with normal cardiotocography (CTG) during labor. Presence or absence of pulsations in the UV were noted and related to perinatal outcome. RESULTS: Pulsations in the UV were seen in eight (30.8%) of the fetuses with pathological CTG, of which six (75%) underwent ODFD. No pulsations were seen in the other 18 (69.2%) fetuses with pathological CTG and these were all delivered without ODFD. No pulsations were seen in the UV in the fetuses with normal CTG and these were all delivered without ODFD. Among the fetuses with pathological CTG, there was an increased risk of ODFD in fetuses with vs. those without pulsations in the UV (P < 0.0001). CONCLUSIONS: Pulsations in the UV can be observed in human fetuses during suspected intrapartum hypoxia and these pulsations are associated with an increased risk of ODFD. Doppler examination of the UV might give important additional information on fetal condition during labor and delivery. Copyright (c) 2009 ISUOG. Published by John Wiley & Sons, Ltd.

Infect Control Hosp Epidemiol. 2009 Jul 7; Eagye KJ, Kuti JL, Nicolau DPObjective. To determine risk factors and outcomes for patients with meropenem high-level-resistant Pseudomonas aeruginosa (MRPA) (minimum inhibitory concentration [Formula: see text] mug/mL). Design. Case-control-control. Setting. An 867-bed urban, teaching hospital. Patients. Fifty-eight MRPA case patients identified from an earlier P. aeruginosa study; 125 randomly selected control patients with meropenem-susceptible P. aeruginosa (MSPA) ([Formula: see text] mug/mL), and 57 control patients without P. aeruginosa (sampled by case date/location). Methods. Patient data, outcomes, and costs were obtained via administrative database. Cases were compared to each control group while controlling for time at risk (days between admission and culture, or entire length of stay [LOS] for patients without P. aeruginosa). Results. A multivariable model predicted risks for MRPA versus MSPA (odds ratio [95% confidence interval]): more admissions (in the prior 12 months) (1.41 [1.15, 1.74]), congestive heart failure (2.19 [1.03, 4.68]), and Foley catheter (2.53 [1.18, 5.45]) (adj. [Formula: see text]). For MRPA versus no P. aeruginosa, risks were age (in 5-year increments) (1.17 [1.03, 1.33]), more prior admissions (1.40 [1.08, 1.81]), and more days in the intensive care unit (1.10 [1.03, 1.18]) (adj. [Formula: see text]). Other invasive devices (including mechanical ventilation) and previous antibiotic use (including carbapenems) were nonsignificant. MRPA mortality (31%) did not differ from that of MSPA (15%) when adjusted for time at risk ([Formula: see text]) but did from mortality without P. aeruginosa (9%) ([Formula: see text]). Median LOS and costs were greater for MRPA patients versus MSPA patients and patients without P. aeruginosa: 30 days versus 16 and 10 ([Formula: see text]) and $88,425 versus $28,620 and $22,605 ([Formula: see text]). Conclusions. Although antibiotic use has been shown to promote resistance, our data found that prior antibiotic use was not associated with MRPA acquisition. However, admission frequency and Foley catheters were, suggesting that infection control measures are essential to reducing MRPA transmission.

J Natl Med Assoc. 2009 Jun; 101(6): 536-40Williams RAOBJECTIVES: To review the current status of cardiovascular disease (CVD) in African American women compared to Caucasian women in regards to 4 categories of CVD: coronary artery disease (CAD), hypertension, stroke, and congestive heart failure (CHF), and to call attention to the need to place more emphasis on the need to increase awareness of CVD as the greatest killer of African American females in the United States. METHODS: A review of the recent literature on the subject of CVD in women over the past several years was conducted with a focus on CVD in African American women. Statistical data on incidence, prevalence, morbidity and mortality of CAD, hypertension, stroke, and CHF in black and white women were compared. RESULTS: Statistical data gathered over the past several years indicate that African American women have greater mortality than Caucasian women from CAD, hypertension, stroke, and CHF. The mortality rate from CAD is 69% higher in black women than in white women. Mortality for black females from hypertension is 352% higher than for white females. Age-adjusted stroke death rates are 54% higher in African American than in Caucasian women, and the age-adjusted mortality rate per 100,000 is 113.4 vs. 97.5 for black and white women, respectively. Incidence, prevalence, and morbidity figures for CAD, hypertension, stroke, and CHF are all higher for African American females than for Caucasian females. CONCLUSIONS: African American women are at exceptional risk for CVD, and more recognition of this fact as well as greater awareness of the problem should be promulgated and distributed by means of public education programs. Physicians who treat black patients also need to be encouraged to be more aggressive in their efforts to detect patients at risk and to initiate therapy early on in the course of CVD in this sub-population.

Cochrane Database Syst Rev. 2009; CD004434Liu C, Chen J, Gao Y, Deng B, Liu KBACKGROUND: Pulmonary arterial hypertension is a devastating disease, which leads to right heart failure and premature death. Recent evidence suggests that endothelin receptor antagonists may be promising drugs in the treatment of pulmonary arterial hypertension. OBJECTIVES: To evaluate the efficacy of endothelin receptor antagonists in pulmonary arterial hypertension. SEARCH STRATEGY: We searched CENTRAL (Cochrane Central Register of Controlled Trials), MEDLINE, EMBASE, and the reference section of retrieved articles. Searches are current as of Februray 2008. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-randomised controlled trials involving patients with pulmonary arterial hypertension. DATA COLLECTION AND ANALYSIS: Five review authors independently selected studies, assessed study quality and extracted data. MAIN RESULTS: Five new studies have been added to this updated review, which now includes 11 randomised controlled trials involving 1457 patients. All the trials were of relatively short duration (12 weeks to 6 months). After treatment, patients treated with endothelin receptor antagonists could walk on average 33.7 metres (95% confidence interval [CI] 24.9 to 42.5 metres) further than those treated with placebo in a 6 minute walk test. Endothelin receptor antagonists improved more patients' World Health Organization/New York Heart Association (WHO/NYHA) functional class status than placebo (odds ratio [OR] 1.6; 95% confidence interval [CI] 1.2 to 2.1), and reduced the odds of functional class deterioration compared to placebo (OR 0.26; 95% CI 0.16 to 0.42 ). There was a trend for endothelin receptor antagonists to reduce mortality (OR 0.48; 95% CI 0.21 to 1.09), and limited data suggest that endothelin receptor antagonists improve Borg dyspnoea score and cardiopulmonary haemodynamics in symptomatic patients. Hepatic toxicity was not common, and endothelin receptor antagonists were well tolerated in this population. AUTHORS' CONCLUSIONS: Endothelin receptor antagonists can increase exercise capacity, improve WHO/NYHA functional class, prevent WHO/NYHA functional class deterioration, reduce dyspnoea and improve cardiopulmonary haemodynamic variables in patients with pulmonary arterial hypertension with WHO/NYHA functional class II and III. However, there was only a trend towards endothelin receptor antagonists reducing mortality in patients with pulmonary arterial hypertension. Efficacy data are strongest in those with idiopathic pulmonary hypertension.

Cochrane Database Syst Rev. 2009; CD002865Hapangama D, Neilson JPBACKGROUND: The steroid hormone, progesterone, inhibits contractions of the pregnant uterus at all gestations. Antiprogestins (including mifepristone) have been developed to antagonise the action of progesterone, and have a recognised role in medical termination of early or mid-trimester pregnancy. Animal studies have suggested that mifepristone may also have a role in inducing labour in late pregnancy. OBJECTIVES: To determine the effects of mifepristone for third trimester cervical ripening or induction of labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and reference lists of relevant papers (May 2009). SELECTION CRITERIA: Clinical trials comparing mifepristone used for third trimester cervical ripening or labour induction with placebo/no treatment or other labour induction methods. DATA COLLECTION AND ANALYSIS: A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. For this update, two review authors independently assessed trial quality and extracted data. MAIN RESULTS: Ten trials (1108 women) are included. Compared to placebo, mifepristone treated women were more likely to be in labour or to have a favourable cervix at 48 hours (risk ratio (RR) 2.41, 95% confidence intervals (CI) 1.70 to 3.42) and this effect persisted at 96 hours (RR 3.40, 95% CI 1.96 to 5.92). They were less likely to need augmentation with oxytocin (RR 0.80, 95% CI 0.66 to 0.97). Mifepristone treated women were less likely to undergo caesarean section (RR 0.74, 95% CI 0.60 to 0.92) but more likely to have an instrumental delivery (RR 1.43, 95% CI 1.04 to 1.96). Women receiving mifepristone were less likely to undergo a caesarean section as a result of failure to induce labour (RR 0.40, 95% CI 0.20 to 0.80). There is insufficient evidence to support a particular dose but a single dose of 200 mg mifepristone appears to be the lowest effective dose for cervical ripening (increased likelihood of cervical ripening at 72 hours (RR 2.13, 95% CI 1.15 to 3.97). Abnormal fetal heart rate patterns were more common after mifepristone treatment (RR 1.85, 95% CI 1.17 to 2.93), but there was no evidence of differences in other neonatal outcomes. There is insufficient information on the occurrence of uterine rupture/dehiscence in the reviewed studies. AUTHORS' CONCLUSIONS: There is insufficient information available from clinical trials to support the use of mifepristone to induce labour. However, the studies suggest that mifepristone is better than placebo in reducing the likelihood of caesarean sections being performed for failed induction of labour; therefore, this may justify future trials comparing mifepristone with the routine cervical ripening agents currently in use. There is little information on effects on the baby.

Health Technol Assess. 2009 Jul; 13(32): 1-232Mant J, Doust J, Roalfe A, Barton P, Cowie M, Glasziou P, Mant D, McManus R, Holder R, Deeks J, Fletcher K, Qume M, Sohanpal S, Sanders S, Hobbs FOBJECTIVES: To assess the accuracy in diagnosing heart failure of clinical features and potential primary care investigations, and to perform a decision analysis to test the impact of plausible diagnostic strategies on costs and diagnostic yield in the UK health-care setting. DATA SOURCES: MEDLINE and CINAHL were searched from inception to 7 July 2006. 'Grey literature' databases and conference proceedings were searched and authors of relevant studies contacted for data that could not be extracted from the published papers. REVIEW METHODS: A systematic review of the clinical evidence was carried out according to standard methods. Individual patient data (IPD) analysis was performed on nine studies, and a logistic regression model to predict heart failure was developed on one of the data sets and validated on the other data sets. Cost-effectiveness modelling was based on a decision tree that compared different plausible investigation strategies. RESULTS: Dyspnoea was the only symptom or sign with high sensitivity (89%), but it had poor specificity (51%). Clinical features with relatively high specificity included history of myocardial infarction (89%), orthopnoea (89%), oedema (72%), elevated jugular venous pressure (70%), cardiomegaly (85%), added heart sounds (99%), lung crepitations (81%) and hepatomegaly (97%). However, the sensitivity of these features was low, ranging from 11% (added heart sounds) to 53% (oedema). Electrocardiography (ECG), B-type natriuretic peptides (BNP) and N-terminal pro-B-type natriuretic peptides (NT-proBNP) all had high sensitivities (89%, 93% and 93% respectively). Chest X-ray was moderately specific (76-83%) but insensitive (67-68%). BNP was more accurate than ECG, with a relative diagnostic odds ratio of ECG/BNP of 0.32 (95% CI 0.12-0.87). There was no difference between the diagnostic accuracy of BNP and NT-proBNP. A model based upon simple clinical features and BNP derived from one data set was found to have good validity when applied to other data sets. A model substituting ECG for BNP was less predictive. From this a simple clinical rule was developed: in a patient presenting with symptoms such as breathlessness in whom heart failure is suspected, refer directly to echocardiography if the patient has a history of myocardial infarction or basal crepitations or is a male with ankle oedema; otherwise, carry out a BNP test and refer for echocardiography depending on the results of the test. On the basis of the cost-effectiveness analysis carried out, such a decision rule is likely to be considered cost-effective to the NHS in terms of cost per additional case detected. The cost-effectiveness analysis further suggested that, if likely benefit to the patient in terms of improved life expectancy is taken into account, the optimum strategy would be to refer all patients with symptoms suggestive of heart failure directly for echocardiography. CONCLUSIONS: The analysis suggests the need for important changes to the NICE recommendations. First, BNP (or NT-proBNP) should be recommended over ECG and, second, some patients should be referred straight for echocardiography without undergoing any preliminary investigation. Future work should include evaluation of the clinical rule described above in clinical practice.

Ann Thorac Surg. 2009 Jul; 88(1 Suppl): S43-62Shahian DM, O'Brien SM, Filardo G, Ferraris VA, Haan CK, Rich JB, Normand SL, DeLong ER, Shewan CM, Dokholyan RS, Peterson ED, Edwards FH, Anderson RP, BACKGROUND: Since 1999, The Society of Thoracic Surgeons (STS) has published two risk models that can be used to adjust the results of valve surgery combined with coronary artery bypass graft surgery (CABG). The most recent was developed from data for patients who had surgery between 1994 and 1997 using operative mortality as the only endpoint. Furthermore, this model did not specifically consider mitral valve repair plus CABG, an increasingly common procedure. Consistent with STS policy of periodically updating and improving its risk models, new models for valve surgery combined with CABG have been developed. These models specifically address both perioperative morbidity and mitral valve repair, and they are based on contemporary data. METHODS: The final study population consisted of 101,661 procedures, including aortic valve replacement (AVR) plus CABG, mitral valve replacement (MVR) plus CABG, or mitral valve repair (MVRepair) plus CABG between January 1, 2002, and December 31, 2006. Model outcomes included operative mortality, stroke, deep sternal wound infection, reoperation, prolonged ventilation, renal failure, composite major morbidity or mortality, prolonged postoperative length of stay, and short postoperative length of stay. Candidate variables were screened for frequency of missing data, and imputation techniques were used where appropriate. Stepwise variable selection was employed, supplemented by advice from an expert panel of cardiac surgeons and biostatisticians. Several variables were forced into models to insure face validity (eg, atrial fibrillation for the permanent stroke model, sex for all models). Based on preliminary analyses of the data, a single model was employed for valve plus CABG, with indicator variables for the specific type of procedure. Interaction terms were included to allow for differential impact of predictor variables depending on procedure type. After validating the model in the 40% validation sample, the development and validation samples were then combined, and the final model coefficients were estimated using the overall 100% combined sample. The final logistic regression model was estimated using generalized estimating equations to account for clustering of patients within institutions. RESULTS: The c-index for mortality prediction for the overall valve plus CABG population was 0.75. Morbidity model c-indices for specific complications (permanent stroke, renal failure, prolonged ventilation > 24 hours, deep sternal wound infection, reoperation for any reason, major morbidity or mortality composite, and prolonged postoperative length of stay) for the overall group of valve plus CABG procedures ranged from 0.622 to 0.724, and calibration was excellent. CONCLUSIONS: New STS risk models have been developed for heart valve surgery combined with CABG. These are the first valve plus CABG models that also include risk prediction for individual major morbidities, composite major morbidity or mortality, and short and prolonged length of stay.

Eur J Echocardiogr. 2009 Jul; 10(5): 732-5Iriart X, Jalal Z, Derval N, Latrabe V, Thambo JBA 13-year-old boy was admitted to our department after an out-of-hospital cardiac arrest during physical exertion. Transitory ST-segment elevation in the anterior chest leads was noted after defibrillation. At 48 h, initial evaluation was performed. Twelve-lead EKG and telemetry were normal. Transthoracic echocardiography showed normal left ventricle (LV) size and global function. Segmental two-dimensional (2D) longitudinal strain of the anterior wall was significantly decreased when compared with the other segments, and was associated with post-systolic shortening. Coronary angiography and 64-slice computed tomography revealed an anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). ALCAPA is a rare congenital malformation. The usual clinical course is a severe left-sided heart failure and mitral valve insufficiency presenting during the first months of life. In some cases, collateral blood supply from the right coronary artery is sufficient and symptoms may be subtle or even absent. However, ventricular arrhythmias or sudden cardiac death during exercise may be the first clinical presentation in patients with ALCAPA. Indirect evidence suggests that myocardial ischaemia is the underlying aetiology of cardiac ventricular ischaemia in patients with ALCAPA. Post-systolic shortening and altered longitudinal strain have recently been described as potential useful markers of ischaemic dysfunction in patients with ischaemic heart disease. In this case report, we demonstrate the usefulness of 2D strain as a non-invasive tool to assess subclinical myocardial ischaemia in patients with an ALCAPA. This provides further supportive evidence for the role of cardiac ischaemia in aetiology of ventricular arrhythmia in this rare condition.

Pacing Clin Electrophysiol. 2009 Jul; 32(7): 879-87Foo D, Walker BD, Kuchar DL, Thorburn CW, Tay A, Hayward CS, Macdonald P, Keogh A, Kotlyar E, Spratt P, Jansz PBackground: Nonpulsatile left ventricular assist devices (LVADs) are increasingly used for treatment of refractory heart failure. A majority of such patients have implanted cardiac devices, namely implantable cardioverter-defibrillators (ICDs) or cardiac resynchronization therapy-pacemaker (CRT-P) or cardiac resynchronization therapy-defibrillator (CRT-D) devices. However, potential interactions between LVADs and cardiac devices in this category of patients remain unknown. Methods: We reviewed case records and device logs of 15 patients with ICDs or CRT-P or CRT-D devices who subsequently had implantation of a VentrAssist LVAD (Ventracor Ltd., Chatswood, Australia) as destination therapy or bridge to heart transplantation. Pacemaker and ICD lead parameters before and after LVAD implant were compared. In addition, ventricular tachyarrhythmia event logs and potential electromagnetic interference reports were evaluated. Results: Right ventricular (RV) sensing decreased in the first 6 months post-LVAD. Mean R-wave amplitude preimplant was 10.9 +/- 5.25 mV compared with 7.2 +/- 3.4 mV during follow-up (P = 0.02). RV impedance also decreased from 642 +/- 240 ohms at baseline to 580 +/- 212 ohms at follow-up (P = 0.007). There was a significant increase in RV stimulation threshold following implantation of the LVAD from 0.8 +/- 0.6 V at baseline to 1.4 +/- 1.0 V in the first 6 months postimplant (P = 0.01). A marked increase in ventricular tachyarrhythmia burden was observed in three patients. One patient displayed electromagnetic interference between the LVAD and defibrillator, resulting in inappropriate defibrillation therapy. Conclusions: LVADs have a definite impact on cardiac devices in respect with alteration of lead parameters, ventricular tachyarrhythmias, and electromagnetic interference.

Chest. 2009 Jun 30; Khayat RN, Abraham WT, Patt B, Pu M, Jarjoura DBackground Treatment of obstructive sleep apnea (OSA) in outpatients with systolic heart failure improves cardiac function. We evaluated the impact of immediate inpatient diagnosis and treatment of OSA in hospitalized patients with acutely decompensated heart failure (ADHF) on in-hospital cardiac outcomes. Methods A pilot randomized controlled trial conducted in an academic heart hospital. Patients with ADHF underwent an attended in-hospital sleep study within two days of admission to establish the diagnosis of Sleep Disordered Breathing. Participants were 46 consecutive ADHF patients who had OSA (apnea-hypopnea index >/=15 events/h). Participants were randomized to either intervention arm (n = 23) with in-hospital treatment of OSA using auto-adjusting positive airway pressure along with standard treatment of ADHF, or to a control arm (n = 23) which received only standard treatment for ADHF. The primary outcome was the change in left ventricular ejection fraction (LVEF) three nights post randomization. Results The change in LVEF from baseline to three days post randomization in the intervention arm was significantly superior to the control group. The difference in LVEF improvement was 4.6% (p = 0.03). LVEF increased in the intervention group by 4.5% (se = 1.7). LVEF change in the control arm was -0.3% (se = 1.5). The difference in LVEF improvement between the two groups persisted after adjustment for baseline LVEF, type of cardiomyopathy, body mass index, AHI, and sex. Conclusions An approach of early identification and in-hospital treatment of OSA in patients with ADHF is feasible and resulted in improvement in systolic function. The impact of this approach on out of hospital outcomes requires further investigation.

PLoS One. 2009; 4(7): e6117Palpant NJ, Szatkowski ML, Wang W, Townsend D, Bedada FB, Koch LG, Britton SL, Metzger JMOxygen metabolism is a strong predictor of the general health and fitness of an organism. In this study, we hypothesized that a divergence in intrinsic aerobic fitness would co-segregate with susceptibility for cardiovascular dysfunction. To test this hypothesis, cardiac function was assessed in rats specifically selected over nineteen generations for their low (LCR) and high (HCR) intrinsic aerobic running capacity. As an integrative marker of native aerobic capacity, run time to exhaustion between LCR and HCR rats had markedly diverged by 436% at generation nineteen of artificial selection. In vivo assessment of baseline cardiac function by echocardiography and catheter-based conductance micromanometry showed no marked difference in cardiac performance. However, when challenged by exposure to acute hypoxia, cardiac pump failure occurred significantly earlier in LCR rats compared to HCR animals. Acute cardiac decompensation in LCR rats was exclusively due to the development of intractable irregular ventricular contractions. Analysis of isolated cardiac myocytes showed significantly slower sarcomeric relaxation and delayed kinetics of calcium cycling in LCR myocytes compared to HCR myocytes. This study also revealed that artificial selection for low native aerobic capacity is a novel pathologic stimulus that results in myosin heavy chain isoform switching in the heart as shown by increased levels of beta-MHC in LCR rats. Together, these results provide evidence that alterations in sub-cellular calcium handling and MHC isoform composition are associated with susceptibility to compensatory cardiac remodeling and hypoxia induced pump failure in animals with low intrinsic aerobic capacity.

Wien Klin Wochenschr. 2009; 121(9-10): 309-13Lainscak M, Hodoscek LM, Düngen HD, Rauchhaus M, Doehner W, Anker SD, von Haehling SOBJECTIVES: Like chronic heart failure, chronic obstructive pulmonary disease (COPD) is an enormous public health problem in industrialized countries. Our aim was to determine the prevalence and clinical impact of COPD among patients hospitalized for heart failure in a community hospital serving a population of 125,000 people. METHODS: Between 2001 and 2003 a total of 638 patients (73 +/- 10 years, 48% men, 74% NYHA class III) were identified with a discharge diagnosis of heart failure. Medical charts were reviewed and vital status was obtained from a Central Population Registry. RESULTS: COPD was diagnosed in 106 (17%) patients whose age was similar to those without COPD (73 +/- 9 vs. 73 +/- 11 years, P = 0.35). Patients with COPD were more often males (65% vs. 45%, P < 0.001). There were no differences in arterial hypertension, atrial fibrillation, diabetes mellitus and most laboratory markers except hemoglobin (141 +/- 20 vs. 132 +/- 20 g/l, P < 0.001) and uric acid (453 +/- 136 vs. 414 +/- 139 mmol/l, P = 0.013). At discharge, patients with COPD were less likely to receive beta-blockers (12% vs. 28%, odds ratio 0.35, 95% CI0.19-0.64). During follow-up, patients with COPD had higher mortality (73% vs. 60%, P = 0.016, hazard ratio 1.48, 95% CI 1.15-1.90). Kaplan-Meier (log-rank test, P = 0.002) and Cox proportional hazard analysis, adjusted for age, sex, hemoglobin, uric acid, and treatment with beta-blockers and furosemide (hazard ratio 1.38, 95% CI1.04-1.83, P = 0.024) demonstrated the prognostic importance of COPD. CONCLUSIONS: COPD is frequent among hospitalized patients with heart failure. Beta-blockers are largely underused, which is probably a major reason for the higher mortality observed in patients with concomitant chronic heart failure and COPD.

Zhonghua Er Ke Za Zhi. 2009 May; 47(5): 338-343He YX, Fu D, Cao DZ, Liu HY, Huang QL, Li CROBJECTIVE: To discuss the treatment strategy of severe hand-foot-and-mouth disease (HFMD) cases, prevent the severe cases from progressing to fatal condition and enhance the survival rate of critically ill patients. METHODS: Eighty HFMD cases were divided into four groups, A, B, C and D, according to the severity of patients' nervous system manifestation and other system involved. Different intensive care and treatments were used and the effect and outcome were analyzed for each group. All statistical analyses were performed by using SPSS software 13.0. One-way ANOVA and Chi-square test were used for data analysis. RESULTS: The most common symptoms were continuous fever (69/70) and myoclonic jerk (67/70). The fewer the rashes were, the more severe the patient's condition was, heart rate >200/min, hypertension, increase of white blood cells in peripheral blood and hyperglycemia were common in patients with lesions in brain stem and pulmonary edema. There were no relations between patient's conditions and CSF white blood cells and CRP. CNS involvement was highly associated with EV71 infection. There were 69 cases in group A, B and C in total and all recovered. Of 11 patients in group D, 6 got complicated neurogenic pulmonary edema and circulatory failure, 2 cases died and 9 cases survived, 8 cases recovered without sequelae while one case had sequelae of mental retardation and dyscinesia. CONCLUSION: Administration of mannitol, methylprednisolone, IVIG and other supportive treatments in time and reasonably might have advantages in avoiding aggravation of the condition and enhancing the rate of successful rescue in patients with nervous system involvement.

Pacing Clin Electrophysiol. 2009 Jul; 32(7): 913-917Mollema SA, Klein P, Heersche J, Schalij MJ, VAN DER Wall EE, Versteegh MI, Klautz RJ, VAN Erven L, Bax JJBackground: Besides implantation of an implantable cardioverter-defibrillator (ICD), a proportion of patients with left ventricular (LV) dysfunction due to ischemic cardiomyopathy are potential candidates for surgical LV reconstruction (Dor procedure), which changes LV ejection fraction (LVEF) considerably. In these patients, LVEF as selection criterium for ICD implantation may be difficult. This study aimed to determine the value of LVEF as criterium for ICD implantation in heart failure patients undergoing surgical LV reconstruction. Methods: Consecutive patients with end-stage heart failure who underwent ICD implantation and LV reconstruction were evaluated. During admission, two-dimensional (2D) echocardiography (LV volumes and LVEF) was performed before surgery and was repeated at 3 months after surgery. Over a median follow-up of 18 months, the incidence of ICD therapy was evaluated. Results: The study population consisted of 37 patients (59 +/- 11 years). At baseline, mean LVEF was 23 +/- 5%. Mean left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) were 175 +/- 73 mL and 225 +/- 88 mL, respectively. At 3-month follow-up, mean LVEF was 41 +/- 9% (P < 0.0001 vs. baseline), and mean LVESV and LVEDV were 108 +/- 65 mL and 176 +/- 73 mL, respectively (P < 0.0001 vs. baseline). During 18-month follow-up, 12 (32%) patients had ventricular arrhythmias, resulting in appropriate ICD therapy. No significant relations existed between baseline LVEF (P = 0.77), LVEF at 3-month follow-up (P = 0.34), change in LVEF from baseline to 3-month follow-up (P = 0.28), and the occurrence of ICD therapy during 18-month follow-up. Conclusion: LVEF before and after surgical LV reconstruction is of limited use as criterium for ICD implantation in patients with end-stage heart failure.

Implement Sci. 2009 Jul 2; 4(1): 36Gagliardi AR, Brouwers MC, Palda VA, Lemieux-Charles L, Grimshaw JMABSTRACT: BACKGROUND: Practice guidelines can improve health care delivery and outcomes but several issues challenge guideline adoption, including their intrinsic attributes, and whether and how they are implemented. It appears that guideline format may influence accessibility and ease of use, which may overcome attitudinal barriers of guideline adoption, and appear to be important to all stakeholders. Guideline content may facilitate various forms of decision making about guideline adoption relevant to different stakeholders. Knowledge and attitudes about, and incentives and capacity for implementation on the part of guideline sponsors may influence whether and how they develop guidelines containing these features, and undertake implementation. Examination of these issues may yield opportunities to improve guideline adoption. METHODS: The attributes hypothesized to facilitate adoption will be expanded by thematic analysis, and quantitative and qualitative summary of the content of international guidelines for two primary care (diabetes, hypertension) and institutional care (chronic ulcer, chronic heart failure) topics. Factors that influence whether and how guidelines are implemented will be explored by qualitative analysis of interviews with individuals affiliated with guideline sponsoring agencies. DISCUSSION: Previous research examined guideline implementation by measuring rates of compliance with recommendations or associated outcomes but this produced little insight on how the products themselves, or their implementation could be improved. This research will establish a theoretical basis upon which to conduct experimental studies to compare the cost-effectiveness of interventions that enhance guideline development and implementation capacity. Such studies could first examine short-term outcomes predictive of guideline utilization such as recall, attitude to, confidence in, and adoption intention. If successful, then long-term objective outcomes reflecting the adoption of processes and associated patient care outcomes could be evaluated.

Eur J Heart Fail. 2009 Jul; 11(7): 668-75Nadji G, Rusinaru D, Rémadi JP, Jeu A, Sorel C, Tribouilloy CAIMS: Although congestive heart failure (CHF) represents the most common cause of death in native valve infective endocarditis (IE), recent data on the outcome of IE complicated by CHF are lacking. We aimed to analyse the characteristics and prognosis of patients with left-sided native valve IE complicated by CHF and to evaluate the impact of early surgery on 1 year outcome. METHODS AND RESULTS: Two hundred and fifty-nine consecutive patients with definite left-sided native valve IE according to the Duke criteria were included in this analysis. When compared with patients without CHF (n = 151), new heart murmur, high comorbidity index, aortic valve IE, and severe valve regurgitation were more frequently observed in CHF patients (n = 108, 41.6%). Mitral valve IE, embolic events and neurological events were less frequent in CHF patients. Congestive heart failure was independently predictive of in-hospital [OR 3.8 (1.7-9.0); P = 0.0013] and 1 year mortality [HR 1.8 (1.1-3.0); P = 0.007]. Early surgery was performed in 46% of CHF patients with a peri-operative mortality of 10%. In the CHF group, comorbidity index, Staphylococcus aureus IE, uncontrolled infection, and major neurological events were univariate predictors of 1 year mortality. Early surgery was independently associated with improved 1 year survival [HR 0.45 (0.22-0.93); P = 0.03]. CONCLUSION: Left-sided native valve IE complicated by CHF is more frequent in aortic IE and is associated with severe regurgitation. Congestive heart failure is an independent predictor of in-hospital and 1 year mortality. In CHF patients, early surgery is independently associated with reduced mortality and should be widely considered to improve outcome.

Anesthesiology. 2009 Jun 29; Fellahi JL, Hanouz JL, Manach YL, Gué X, Monier E, Guillou L, Riou BBACKGROUND:: Simultaneous assessment of cardiac troponin I, B-type natriuretic peptide, and C-reactive protein has been found to provide unique prognostic information in acute coronary syndromes. The current study addressed the prognostic implication of a multiple-marker approach in cardiac surgery. METHODS:: Two hundred twenty-four patients undergoing cardiac surgery were included and followed up within 12 months after surgery. Serial blood samples were drawn in all patients the day before surgery, at the end of surgery, and 6, 24, and 120 h after surgery. Major adverse cardiac events within 12 months after surgery were chosen as study endpoints and were defined as malignant ventricular arrhythmia, myocardial infarction, congestive heart failure, the need for myocardial revascularization, and/or death from cardiac cause. Predictive ability of each cardiac biomarker was assessed using logistic regression. RESULTS:: Accuracies of C-reactive protein, cardiac troponin I, and B-type natriuretic peptide, considered as continuous variables, to predict the occurrence of major adverse cardiac events were limited (area under receiver operating characteristic curve: 0.54[0.47-0.60], P = 0.42; 0.62[0.55-0.68], P = 0.01; and 0.68[0.61-0.74], P < 0.001, respectively). When biomarkers were considered as 75% specificity dichotomized variables, elevated C-reactive protein (> 180 mg/l), cardiac troponin I (> 3.5 ng/ml), and B-type natriuretic peptide (> 880 pg/ml) were independent predictors of major adverse cardiac events (odds ratio: 2.14[1.03-4.49], P = 0.043; 2.37[1.25-5.64], P = 0.011; and 2.65[1.16-4.85], P = 0.018, respectively) in a multivariate model including the European System for Cardiac Operative Risk Evaluation score. CONCLUSIONS:: Simultaneous measurement of cardiac troponin I, B-type natriuretic peptide, and C-reactive protein improves the risk assessment of long-term adverse cardiac outcome after cardiac surgery.

Arq Bras Cardiol. 2009 Apr; 92(4): 283-9Huoya Mde O, Penalva RA, Alves SR, Feitosa GS, Gadelha S, Ladeia AMBACKGROUND: Studies comparing inflammatory activity between diabetic and non-diabetic individuals with acute coronary syndrome are scarce, and none including only patients with unstable angina (UA) has been published to date. OBJECTIVE: We compared serum C-reactive protein (CRP), and interleukin-6(IL-6) between diabetic and non-diabetic patients with unstable angina (UA) to determine if difference in inflammatory activity is responsible for a worse prognosis in diabetic patients. We also evaluated the correlation between inflammatory markers and the metabolic profile in diabetic patients and the correlation between inflammatory response and in-hospital outcomes: death, acute myocardial infarction, congestive heart failure, and length of stay in hospital. METHODS: A prospective cohort study of 90 consecutive patients admitted to a chest pain unit with UA and divided into two groups, diabetic and non-diabetic. Serum CRP, IL-6, metabolic profile and leukocyte count were measured at hospital arrival. RESULTS: Forty-two patients (47%) were diabetic (age 62+/-9) vs. 48 (53%) non-diabetic (age 63+/-12). No differences between median C-reactive protein (1.78 vs. 2.23 mg/l,p=0.74) and interleukin-6 (0 vs. 0 pg/ml,p=0.31) were found between the two groups. There was a positive correlation between CRP and total cholesterol (rs = 0.21,p = 0.05), CRP and LDL-cholesterol (rs=0.22,p=0.04) and between CRP and leukocyte count (rs = 0.32, p = 0.02) in both groups. No associations were found between inflammatory markers and in-hospital outcomes. CONCLUSION: We found no difference in inflammatory activity between diabetic and non-diabetic patients with UA, suggesting that this clinical condition may result in balanced inflammatory activity between the two groups and increase acute-phase proteins independently of metabolic state.

Ann Pharmacother. 2009 Jun 30; Allen Lapointe NM, Stafford JA, Pappas PA, Al-Khatib SM, Anstrom KJBACKGROUND: Implantable cardioverter defibrillators (ICDs) are indicated for both primary and secondary prevention of sudden cardiac arrest. beta-Blockers are also indicated in most patients who have an indication for an ICD; however, their use in this population is not well described. Some clinicians may be unaware of the recommendation for beta-Blockers in this population. OBJECTIVE: To explore beta-blocker use among ICD recipients. METHODS: Adults who received their first ICD at Duke Hospital between July 1999 and July 2004 for primary or secondary prevention of sudden cardiac arrest were identified. Using hospital data, beta-blocker use was determined at time of discharge, and characteristics of users were compared with those of nonusers. Continued use of beta-blockers after ICD implant was explored in the subset of patients included in the Duke Databank for Cardiovascular Disease (DDCD). RESULTS: The study cohort comprised 804 patients, 652 (81%) with ICD for secondary prevention of sudden cardiac arrest and 152 (19%) for primary prevention. The median age was 65 years and 75% of the patients were men. A total of 544 (68%) received a beta-blocker at time of ICD implant. There were no substantial changes in the proportion of patients with beta-blocker use from 1999 through 2004, overall or within the primary or secondary prevention groups. However, beta-blocker use was higher in the secondary prevention group than in the primary prevention group (69% vs 60%; p = 0.02). A higher proportion of beta-blocker users versus nonusers had ischemic heart disease (82% vs 68%; p < 0.0001), heart failure (84% vs 71%; p < 0.0001), previous myocardial infraction (51% vs 44%; p = 0.05), and ventricular arrhythmias (82% vs 76%; p = 0.04). Of the 425 patients included in the DDCD, only 241 (57%) were receiving beta-blockers at time of implant and during clinical follow-up. CONCLUSIONS: Lower than optimal use of beta-blockers suggests the need for new methods of including evidence-based medications in clinical practice, especially for complex patients for whom numerous clinical practice guidelines may apply.

Ann Pharmacother. 2009 Jun 30; Gareri P, Segura-García C, De Fazio P, De Fazio S, De Sarro GOBJECTIVE: To describe a case of sertraline-induced rhabdomyolysis in an elderly patient with dementia and comorbidities. CASE SUMMARY: A 71-year-old woman visited a psychiatrist in September 2007 for her depressed mood. Her medical history included vascular dementia accompanied by depression, arterial hypertension, and heart failure, as well as cardiac pacemaker implantation several years earlier for severe bradyarrythmia. She had begun taking amisulpride 50 mg/day and diazepam 2 mg at bedtime 6 months prior to the psychiatrist appointment, with poor relief of her depressed mood. Her drug therapy also included nicergoline 30 mg/day, amlodipine 5 mg/day, aspirin 100 mg/day, candesartan 16 mg/day, and atenolol 25 mg/day. At this psychiatrist visit, sertraline 50 mg/day was added for her depression, and was continued after a geriatrician visit in October. Her mood improved significantly. On December 18, 2007, she was admitted to the cardiology unit to undergo a pacemaker replacement. Laboratory tests revealed creatine kinase (CK) 7952 IU/L, lactate dehydrogenase 1021 IU/L, myoglobin 2322 U/L, and aspartate aminotransferase 362 IU/L, resulting in a diagnosis of iatrogenic rhabdomyolysis. Amisulpride and sertraline were discontinued. On December 24, serum CK was 839 IU/L and myoglobin was 91 U/L and the patient was discharged. On January 22, laboratory tests showed normal values of CK, CK-MB, and myoglobin. Sertraline 50 mg/day was again prescribed for the patient's persistent depressed mood. Fifteen days later, blood tests showed CK 1327 IU/L and myoglobin 324 U/L; therefore, the drug was discontinued. CK and myoglobin levels normalized a week later. On April 2, escitalopram was started. At time of writing, there was no evidence of any increase in CK, myoglobin, or other markers of rhabdomyolysis. DISCUSSION: The Naranjo probability scale indicated a probable relationship between sertraline treatment and the onset of rhabdomyolysis. No relationship between amisulpride and rhabdomyolysis was found. Furthermore, rechallenge with sertraline caused CK and myoglobin to again increase, which was reversed following a discontinuation of sertraline. The patient's other comorbidities and medications have not been suggested as possible interactions with sertraline that can cause rhabdomyolysis. Genetic defects of sertraline demethylation and/or P-glycoprotein binding or concurrent circumstances may explain the onset of rhabdomyolysis in this particular patient. CONCLUSIONS: This patient's rhabdomyolysis was probably induced by sertraline therapy.

Arq Bras Cardiol. 2009 Apr; 92(4): 283-9Huoya Mde O, Penalva RA, Alves SR, Feitosa GS, Gadelha S, Ladeia AMBACKGROUND: Studies comparing inflammatory activity between diabetic and non-diabetic individuals with acute coronary syndrome are scarce, and none including only patients with unstable angina (UA) has been published to date. OBJECTIVE: We compared serum C-reactive protein (CRP), and interleukin-6(IL-6) between diabetic and non-diabetic patients with unstable angina (UA) to determine if difference in inflammatory activity is responsible for a worse prognosis in diabetic patients. We also evaluated the correlation between inflammatory markers and the metabolic profile in diabetic patients and the correlation between inflammatory response and in-hospital outcomes: death, acute myocardial infarction, congestive heart failure, and length of stay in hospital. METHODS: A prospective cohort study of 90 consecutive patients admitted to a chest pain unit with UA and divided into two groups, diabetic and non-diabetic. Serum CRP, IL-6, metabolic profile and leukocyte count were measured at hospital arrival. RESULTS: Forty-two patients (47%) were diabetic (age 62+/-9) vs. 48 (53%) non-diabetic (age 63+/-12). No differences between median C-reactive protein (1.78 vs. 2.23mg/l,p=0.74) and interleukin-6 (0 vs. 0pg/ml,p=0.31) were found between the two groups. There was a positive correlation between CRP and total cholesterol (rs = 0.21,p = 0.05), CRP and LDL-cholesterol (rs=0.22,p=0.04) and between CRP and leukocyte count (rs = 0.32, p = 0.02) in both groups. No associations were found between inflammatory markers and in-hospital outcomes. CONCLUSION: We found no difference in inflammatory activity between diabetic and non-diabetic patients with UA, suggesting that this clinical condition may result in balanced inflammatory activity between the two groups and increase acute-phase proteins independently of metabolic state.

J Heart Lung Transplant. 2009 Jul; 28(7): 704-9Kittleson MM, Skojec DV, Wittstein IS, Champion HC, Judge DP, Barouch LA, Halushka M, Hare JM, Kasper EK, Russell SDBACKGROUND: B-type natriuretic peptide (BNP) correlates with cardiac filling pressures and outcomes in patients with heart failure. In heart transplant recipients, we hypothesize that a within-individual change in BNP over time would be more helpful than absolute BNP in detecting International Society of Heart and Lung Transplantation (ISHLT) grade 2R or greater rejection. METHODS: N-terminal pro-BNP (NT-proBNP) levels were measured in 146 consecutive transplant recipients undergoing routine endomyocardial biopsies. In the cross-sectional analysis, multiple observations per individual were accounted for using generalized estimation equations. RESULTS: A cross-sectional analysis demonstrated a weak association between NT-proBNP levels and rejection, with an odds ratio (OR) of 1.01 for every 100-pg/mL increase in NT-proBNP (p = 0.02). However, with a doubling of an individual's NT-proBNP level, the OR for significant rejection was 2.9 (95% confidence interval [CI] 1.2-7.0), the OR with a 5-fold increase was 9.1 (95% CI, 2.7-31.5), and the OR with a 10-fold increase was 27.7 (95% CI, 5.9-129). A 10-fold increase in NT-proBNP offered a negative predictive value of 95% for the diagnosis of rejection. The relationship between within-individual increases in NT-proBNP and rejection persisted after adjusting for a fall in ejection fraction and a rise pulmonary capillary wedge pressure, and was a stronger predictor than changes in these parameters. CONCLUSIONS: There is a strong, graded relationship between the within-individual increase in NT-proBNP and the odds of significant rejection independent of hemodynamic parameters. These results suggest that the change in NT-proBNP rather than absolute BNP levels may offer a non-invasive approach to detect rejection.

J Emerg Trauma Shock. 2009 May; 2(2): 124-8Lata I, Gupta R, Sahu S, Singh HPeripartum cardiomyopathy (PPCM) is a rare life-threatening cardiomyopathy of unknown cause that occurs in the peripartum period in previously healthy women.[1] the symptomatic patients should receive standard therapy for heart failure, managed by a multidisciplinary team. The diagnosis of PPCM rests on the echocardiographic identification of new left ventricular systolic dysfunction during a limited period surrounding parturition. Diagnostic criteria include an ejection fraction of less than 45%, fractional shortening of less than 30%, or both, and end-diastolic dimension of greater than 2.7 cm/m(2) body surface-area. This entity presents a diagnostic challenge because many women in the last month of a normal pregnancy experience dyspnea, fatigue, and pedal edema, symptoms identical to early congestive heart failure. There are no specific criteria for differentiating subtle symptoms of heart failure from normal late pregnancy. Therefore, it is important that a high index of suspicion be maintained to identify the rare case of PPCM as general examination showing symptoms of heart failure with pulmonary edema. PPCM remains a diagnosis of exclusion. No additional specific criteria have been identified to allow distinction between a peripartum patient with new onset heart failure and left ventricular systolic dysfunction as PPCM and another form of dilated cardiomyopathy. Therefore, all other causes of dilated cardiomyopathy with heart failure must be systematically excluded before accepting the designation of PPCM. Recent observations from Haiti[2] suggest that a latent form of PPCM without clinical symptoms might exist. The investigators identified four clinically normal postpartum women with asymptomatic systolic dysfunction on echocardiography, who subsequently either developed clinically detectable dilated cardiomyopathy or improved and completely recovered heart function.

J Cardiopulm Rehabil Prev. 2009 Jun 24; Norman JF, Pozehl BJ, Duncan KA, Hertzog MA, Elokda AS, Krueger SKPURPOSE: Plasma B-type natriuretic peptide (BNP) levels obtained at rest have been previously shown to be correlated with the global functional capacity measures of peak oxygen uptake (&OV0312;O2peak) and the minute ventilation/carbon dioxide (VE/&OV0312;co2) slope. The purpose of this study was to assess the relationship of the plasma BNP level to the rate-pressure product (RPP) as an indicator of central or cardiac work capacity. METHODS: Twenty-two subjects (12 men), mean age 57 +/- 12 years, diagnosed with heart failure (8 ischemic/14 nonischemic) were recruited. All subjects were stable on optimal medical therapy for at least 1 month. Blood samples for BNP level analysis were obtained at rest. Subjects underwent a symptom-limited treadmill exercise test using a ramping protocol while &OV0312;O2, heart rate (HR), and blood pressure (BP) were monitored. Correlation analyses were conducted to assess the relationship of BNP level to RPP level, &OV0312;O2peak, VE/&OV0312;CO2 slope, end-tidal CO2 pressure (PETCO2), and left ventricular ejection fraction (LVEF). RESULTS: Resting BNP levels were significantly correlated with RPP levels (r = -0.69). The BNP level and the RPP level were correlated with &OV0312;O2peak (r = -0.63 and r = 0.66, respectively) and VE/&OV0312;CO2 slope (r = 0.53 and r = -0.54, respectively). The RPP level but not the BNP level was correlated with PETCO2 (r = 0.57). Neither BNP nor RPP levels were well correlated with LVEF (r = -0.26 and r = 0.14, respectively). DISCUSSION: The results of this study suggest that resting plasma BNP level may be a useful clinical measure for evaluating both global functional capacity and myocardial specific work capacity in individuals with heart failure.

Eur J Nucl Med Mol Imaging. 2009 Jun 27; Bajc M, Neilly JB, Miniati M, Schuemichen C, Meignan M, Jonson BPulmonary embolism (PE) can only be diagnosed with imaging techniques, which in practice is performed using ventilation/perfusion scintigraphy (V/P(SCAN)) or multidetector computed tomography of the pulmonary arteries (MDCT). The epidemiology, natural history, pathophysiology and clinical presentation of PE are briefly reviewed. The primary objective of Part 1 of the Task Group's report was to develop a methodological approach to and interpretation criteria for PE. The basic principle for the diagnosis of PE based upon V/P(SCAN) is to recognize lung segments or subsegments without perfusion but preserved ventilation, i.e. mismatch. Ventilation studies are in general performed after inhalation of Krypton or technetium-labelled aerosol of diethylene triamine pentaacetic acid (DTPA) or Technegas. Perfusion studies are performed after intravenous injection of macroaggregated human albumin. Radiation exposure using documented isotope doses is 1.2-2 mSv. Planar and tomographic techniques (V/P(PLANAR) and V/P(SPECT)) are analysed. V/P(SPECT) has higher sensitivity and specificity than V/P(PLANAR). The interpretation of either V/P(PLANAR) or V/P(SPECT) should follow holistic principles rather than obsolete probabilistic rules. PE should be reported when mismatch of more than one subsegment is found. For the diagnosis of chronic PE, V/P(SCAN) is of value. The additional diagnostic yield from V/P(SCAN) includes chronic obstructive lung disease (COPD), heart failure and pneumonia. Pitfalls in V/P(SCAN) interpretation are considered. V/P(SPECT) is strongly preferred to V/P(PLANAR) as the former permits the accurate diagnosis of PE even in the presence of comorbid diseases such as COPD and pneumonia. Technegas is preferred to DTPA in patients with COPD.