Standard Heart Research Articles

24-h ambulatory pulse wave velocity and central blood pressure in type 2 diabetes

BackgroundPulse wave analysis from a brachial cuff permits ambulatory measurements of pulse wave velocity (PWV) and central blood pressure parameters. The diurnal variation of PWV in type 2 diabetes is unknown. MethodsWe evaluated the Arteriograph24 which is a brachial cuff based equipment for estimating PWV and central blood pressure data without the use of a transfer function, in 22 type 2 diabetic patients, who had two 24 h measurements performed. ResultsThe mean number of valid day time and nighttime measurements were 29 (range 16–50) and 18 (11–25), respectively. 21 patients had at least one qualifying report. Nighttime PWV was significantly lower than during the day (9.1 vs. 9.7 ± 0.8 mm/s, p < 0.01). Systolic aortic blood pressure was 6 mmHg lower than brachial blood pressure in the day time (p < 0.01) and 4 mmHg lower during the night (p < 0.05). Each single measurement was standardized with the 24 h average as reference thus generating data from 1004 paired observations. The standardized PWV correlated with standardized values of heart rate (r = 0.24, p < 0.001) and systolic aorta blood pressure (r = 0.20, p < 0.001). A stepwise multiple regression model with standardized pulse wave velocity as dependent variable included standardized heart rate, systolic aorta blood pressure and a dummy variable for day/night status (R2 = 0.091, p < 0.001). ConclusionThe Arteriograph24 is applicable for research purpose. PVW in type 2 diabetes is modestly reduced during the night. The intraindividual variation of heart rate contributed independently to the variation of PWV.

Visit-to-visit variability in systolic blood pressure: correlated with the changes of arterial stiffness and myocardial perfusion in on-treated hypertensive patients

Background: Visit-to-visit variability in blood pressure (BP) was demonstrated to correlate with cardiovascular events independent of mean BP. The goal of the present study was to investigate the correlation of visit-to-visit BP variability with artery stiffness and myocardial perfusion in on-treated hypertensive patients.Methods: BP was measured in 271 hypertensive patients at every visit over the course of the antihypertensive treatment, and the standard deviation (SD), coefficient of variation (CV), maximum, and minimum in serial BP were calculated. Non-invasive pulse wave analysis was performed in all patients.Results: Compared with baseline, carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index (Aix) and Aix adjusted to a “standard heart rate” of 75 beats/min (Aix@HR75) were markedly declined, and sub-endocardial viability ratio (SEVR) was obviously increased in each group (p < 0.001). The changes of cfPWV, SEVR, Aix and Aix@HR75 in patients with lower SD of systolic blood pressure (SBP) were significantly greater than those in patients with higher SD of SBP. And the changes were statistically correlated with both SD and CV of serial SBP during follow-up, even after adjusted for mean SBP and mean diastolic blood pressure (DBP).Conclusion: Visit-to-visit SBP variability is independently correlated with changes of artery stiffness and myocardial perfusion in on-treated hypertensive patients.

Abstract 051: Growth Plasticity Of The Prenatal Murine Heart Depends On Amino Acid Availability

Intrauterine development influences the susceptibility to cardiovascular disease in adulthood, although the underlying molecular mechanisms are vastly unknown. We have recently shown that the prenatal mouse heart has an impressive regenerative capacity in response to tissue mosaicism for mitochondrial dysfunction caused by a heart specific knockout of holocytochrome c synthase (Hccs) - an X-linked gene required for mitochondrial respiration. In heterozygous Hccs knockout (Hccs+/-) embryos, hyperproliferation of healthy cardiomyocytes compensates for the functional loss of 50% of Hccs deficient cells, ensuring formation of a normally contracting heart at birth. In order to uncover molecular mechanisms enabling compensatory growth of the prenatal myocardium, we performed microarray RNA expression analyses on neonatal Hccs+/- and control hearts. These data revealed numerous genes involved in amino acid metabolism and protein homeostasis being differentially expressed in the neonatal Hccs+/- myocardium. We, therefore, hypothesized that amino acid availability is crucial for compensatory growth of Hccs+/- hearts to build a regularly sized organ and allow normal postnatal function. Thus, we studied the effects of in utero amino acid restriction on growth and development of Hccs+/- hearts by feeding dams a low protein diet (LPD) throughout pregnancy and keeping the offspring on LPD until adulthood. On standard protein diet heart weight to body weight ratio of Hccs+/- mice (n=26) born at gestational age 20.5 dpc does not differ compared to littermate controls (n=21). In contrast, Hccs+/- offspring on LPD (n=20) were found to have a significantly reduced heart weight to body weight ratio compared to control animals (n=19) at postnatal day 1. Importantly, cardiomyocyte size and proliferation were unaffected in neonatal Hccs+/- hearts on LPD, suggesting that amino acid restriction rather inhibits prenatal cardiac growth. This was in line with normal heart size and function in adult LPD Hccs+/- mice, confirming normal postnatal development. In conclusion, metabolic adaptations regulating amino acid availability might be required for growth plasticity of the fetal heart to prevent postnatal dysfunction after impaired intrauterine development.

Escaping Immigration Law's Cancellation Catch: Why an Inconclusive Record of Conviction Satisfies the Preponderance of the Evidence Standard in Cancellation of Removal

Hundreds of thousands of non-citizens are removed from the United States every year. A frustrating incompatibility — a catch — lies at the heart of the legal standard that determines whether legal permanent residents (LPRs) who are removable from the United States may qualify for cancellation of removal and thereby remain in the country. There is currently a circuit split over how to interpret this incompatibility. In order to qualify to apply for cancellation of removal, LPRs bear the burden of proving by a preponderance of the evidence that they have not been convicted of an aggravated felony. Whether an LPR has been convicted of an aggravated felony is a legal question, resolved by applying a categorical approach comparing the state statute of conviction with the generic federal definition, or a modified categorical approach that permits examination of a limited number of state court documents. The preponderance of the evidence standard, however, is a factual inquiry with a spectrum of possible levels of proof. Requiring LPRs to prove a matter of law by a preponderance of the evidence actually requires, in essence, proof beyond a reasonable doubt.This article argues that an inconclusive record, which shows that an LPR was convicted of some crime but does not establish that the crime was the equivalent of a federal “aggravated felony,” must carry the alien’s burden of proving by a preponderance of the evidence that she was not convicted of an aggravated felony. This is the only means of harmonizing this internally incompatible and contradictory standard.

Classification Tree for Risk Assessment in Patients Suffering From Congestive Heart Failure via Long-Term Heart Rate Variability

This study aims to develop an automatic classifier for risk assessment in patients suffering from congestive heart failure (CHF). The proposed classifier separates lower risk patients from higher risk ones, using standard long-term heart rate variability (HRV) measures. Patients are labeled as lower or higher risk according to the New York Heart Association classification (NYHA). A retrospective analysis on two public Holter databases was performed, analyzing the data of 12 patients suffering from mild CHF (NYHA I and II), labeled as lower risk, and 32 suffering from severe CHF (NYHA III and IV), labeled as higher risk. Only patients with a fraction of total heartbeats intervals (RR) classified as normal-to-normal (NN) intervals (NN/RR) higher than 80% were selected as eligible in order to have a satisfactory signal quality. Classification and regression tree (CART) was employed to develop the classifiers. A total of 30 higher risk and 11 lower risk patients were included in the analysis. The proposed classification trees achieved a sensitivity and a specificity rate of 93.3% and 63.6%, respectively, in identifying higher risk patients. Finally, the rules obtained by CART are comprehensible and consistent with the consensus showed by previous studies that depressed HRV is a useful tool for risk assessment in patients suffering from CHF.

Changes of the individual heart rate variability under stress for college students with different level of resilience

Objective To study the changes of heart rate variability (HRV) in the Trier Social Stress Test (TSST) among the college students with different level of resilience. Methods Connor-Davidson Resilience Scale (CD-RISC) were used to test the resilience of 160 students in a Military Medical University, and according to the test results, 11 male students with high resilience and 11 students with low resilience were selected to participate the TSST experiment. The test were done according to the TSST standard procedures, heart rate (HR) and HRV were recorded 3 times (before and after the 1st and 25th minutes of TSST). Results ①The low-resilience group’s HR and HRV index were lower (including HRV VLF, LF and HF) than those in high resilience group(P<0.01). ②Compare with the HR baseline values, the HR peaked within the 1st minute of TSST and gradually reduced. The HR ((6.09±8.87)/min) evidently increased in the low-resilience group at the 1st minute (P<0.05). The VLF and HF powers of HRV in the high-resilience group were lower on the 1st minute and significantly higher on the 25th minute (VLF=(15.61±11.81)Hz, HF=(5.48±7.99)Hz, P<0.05). The LF ((84.92±13.30)Hz) power was significantly higher on the 1st minute and peaked on the 25th minute ((89.72±14.93)Hz, P<0.01). The LF/HF ratio (3.43±0.76) increased on the 1st minute and then gradually decreased (1.26±0.23, P<0.01). The VLF, LF and HF powers of HRV in the low-resilience group were significantly higher on the 1st minute. The VLF and LF power continued to increase and they peaked on the 25th minute, whereas the HF power significantly decreased to a minimum on the 25th minute (P<0.01). Within the 1st minute of the experiment, the LF/HF ratio (0.45±0.27) decreased and then gradually increased (1.91±0.40, P<0.01). Conclusion Under stress, individuals with higher resilience have higher HRV to cope with stress effectively and recover quickly. Key words: Heart rate variability; Resilience; Stress

Men Versus Women: Outcome Differences on Cyclosporine and Tacrolimus

Purpose Several registry studies have shown gender differences in outcomes after heart transplantation. The change from cyclosporine (CSA) to tacrolimus (TAC) has improved some outcomes but it is not clear as to its impact on gender differences. In our single center experience with a standardized post heart transplant protocol, we sought to compare the outcomes of men versus women on CSA vs TAC. Methods and Materials Between 1994 and 2009, we evaluated 250 heart transplant patients and divided them into male and female gender groups on CSA vs TAC. The end points included 1-year rejection and 5-year survival, CAV, NF-MACE, nephropathy, hypertension, diabetes, obesity, and malignancy. Results Antibody mediated rejection (AMR) was significantly higher in women on CSA but not on TAC. Serum creatinine was significantly higher in men on TAC but not on CSA but overall (men + women) lower on TAC (p= Conclusions There appears to be gender differences for outcome depending on CSA or TAC immunosuppression. Choice of CSA or TAC for men and women may depend on concern for antibody mediated rejection, renal function and malignancy risk. Men on CSA/MMF (n=71)Women on CSA/MMF (n=15)p-valueMen on TAC/MMF (n=118)Women on TAC/MMF (n=46)p-value5-Year Actuarial Survival, n (%)56 (79%)13 (87%)0.49799 (84%)38 (83%)0.843Creatinine at 1 year, Mean ± SD1.7 ± 0.71.5 ± 0.40.2891.4 ± 0.51.1 ± 0.4

Autonomic dysfunction and circadian blood pressure variations in people with impaired glucose tolerance

To assess circadian blood pressure variability in people with impaired glucose tolerance and a healthy control population. Seventy-five people with impaired glucose tolerance and 40 healthy volunteers (frequency matched on 10-year age bands and sex) underwent a detailed neurological assessment. Autonomic neuropathy was detected by the five standard cardiovascular autonomic tests and heart rate variability was characterized by the triangle index. Diurnal indices were assessed by 24-h ambulatory blood pressure monitoring. Systolic and diastolic diurnal indices were defined as: (mean daytime blood pressure - mean night-time blood pressure) × 100/mean daytime blood pressure. Mean 24-h systolic and diastolic blood pressure was significantly higher in the group with impaired glucose tolerance compared with the control group [126 ± 12 (mean ± SD) vs. 117 ± 10, 75 ± 7 vs. 71 ± 6 mmHg, both P < 0.05). Systolic and diastolic diurnal indices and heart rate variability triangular index were significantly lower in people with impaired glucose tolerance compared with control subjects (9.1 ± 7.8 vs. 13.2 ± 5.4, 14.5 ± 9.7 vs. 18.4 ± 7.1 mmHg, 28.0 ± 8.4 vs. 39.5 ± 9.3, all P < 0.05). Differences in mean diastolic blood pressure, heart rate variability triangular index and the frequency of non-dippers between those with impaired glucose tolerance and control subjects seemed to be independent of BMI and the presence of cardiovascular autonomic neuropathy, as simultaneous adjustment for BMI and cardiovascular autonomic neuropathy had no major effect on the results. Our data suggest that people with impaired glucose tolerance have increased diastolic blood pressure and abnormal circadian blood pressure regulation, independent of obesity and the presence of cardiovascular autonomic neuropathy.

Improving Coronary Stent Biocompatibility with Plasma Deposited High Nitrogen Polymer Coating

may be incorrect at high PVR values. This study sought to determine the accuracy of TTE PVR assessment compared to RHC. Methods: Patients undergoing a RHC assessment of pulmonary hypertension had TTE derived right heart pressure measurements performed the same day. Standard RHC and TTE right heart parameters were measured. RHC PVR was calculated using the formula PVR= [(mPAP−PCWP)/CO]× 80 dynes s cm−5. TTE PVR was calculated using the formula PVR=TRV× 10/TVI RVOT. Echocardiographers were blinded to the invasive data. Results: 100 patients were prospectively recruited. 77/100 had pulmonary hypertension (mean pulmonary artery pressure≥ 25mmHg). Two patients excluded in TTE arm due to no TR. Quality of TR signal envelope: complete 61%, incomplete 36%, absent 2%. Rhythm: Sinus 76%, AF 16%, paced 8%. Measurements (mean±SD): Age= 58.2± 13.6 years. Weight = 79± 19.4 kg. mPAP=34.1± 15mmHg.Time interval between RHC and TTE (mean±SEM)= 140.5± 11.3min. RHC PVR (mean±SEM)= 330.6± 36.1 dynes s cm−5. TTE PVR (mean±SEM)= 208.8± 10.3 dynes s cm−5. Correlation r= 0.7, p< 0.0001. Bland Altman (mean± 1.96 SDs) =−127.4± 457.2 to −711.9 dynes s cm−5. Conclusion: TTE guided assessment of PVR underestimates true RHC determined PVR by a mean of 127 dynes s cm-5 or 1.6 Woods Units (WU). The estimation becomes inaccurate once the PVR is approximately 200 dynes s cm−5 (2.5 WU) or above. The formula PVR=TRV× 10/TVI RVOT should not be used to estimate PVR in patients with known pulmonary hypertension. http://dx.doi.org/10.1016/j.hlc.2013.05.484

Heart rate variability and target organ damage in hypertensive patients

BackgroundWe evaluated the association between linear standard Heart Rate Variability (HRV) measures and vascular, renal and cardiac target organ damage (TOD).MethodsA retrospective analysis was performed including 200 patients registered in the Regione Campania network (aged 62.4 ± 12, male 64%). HRV analysis was performed by 24-h holter ECG. Renal damage was assessed by estimated glomerular filtration rate (eGFR), vascular damage by carotid intima-media thickness (IMT), and cardiac damage by left ventricular mass index.ResultsSignificantly lower values of the ratio of low to high frequency power (LF/HF) were found in the patients with moderate or severe eGFR (p-value < 0.001). Similarly, depressed values of indexes of the overall autonomic modulation on heart were found in patients with plaque compared to those with a normal IMT (p-value <0.05). These associations remained significant after adjustment for other factors known to contribute to the development of target organ damage, such as age. Moreover, depressed LF/HF was found also in patients with left ventricular hypertrophy but this association was not significant after adjustment for other factors.ConclusionsDepressed HRV appeared to be associated with vascular and renal TOD, suggesting the involvement of autonomic imbalance in the TOD. However, as the mechanisms by which abnormal autonomic balance may lead to TOD, and, particularly, to renal organ damage are not clearly known, further prospective studies with longitudinal design are needed to determine the association between HRV and the development of TOD.

Immediate newborn outcome and mode of delivery: Use of standardized fetal heart rate pattern management

Objective: To determine whether a rule-based system for fetal heart rate interpretation can result in reduced metabolic acidemia without increasing obstetrical intervention. Methods: Rates of vacuum-assisted delivery and Cesarean sections, and umbilical artery pH and base excess values were determined over a 5-year period in a single hospital with 3907 deliveries in Japan. Results were compared for 2 years before and 2 years after a 6-month training period in rule-based fetal heart rate interpretation. Results: The pre- and post-training rates of unscheduled Cesarean deliveries (4.8% vs. 6.0%) and vacuum deliveries (21.2% vs. 18.1%) did not differ significantly. The rates of umbilical arterial pH <7.15 (1.51% vs. 0.18%, p < 0.05) and base excess <–12 mEq/L (1.76% vs. 0.25%, p < 0.05) were significantly lower after training. Conclusion: A standardized fetal heart rate pattern management system was associated with a 7-fold reduction of newborn metabolic acidemia with no change in operative intervention.

Predictors of acute cardiac complications in emergency department patients with chest painStatus: PendingCategory: Prognostication

Purpose: Patients presenting to the emergency department (ED) with chest pain have varying levels of risk of complications in the acute phase of treatment (<72h). Early stratification of risk would improve treatment strategies as well as help determine proper level of monitoring. Previous work has indicated that commonly obtained clinical parameters as well as standard heart rate variability (HRV) metrics predict mortality and acute complications in patients with chest pain presenting to the ED; we aimed to determine if the addition of 12-lead ECG parameters would improve the ability to predict these events.

Extended mild hypothermic aortic surgery†

We read with great interest the report by Urbanski et al. [1] on their approach to mild hypothermic aortic arch surgery and the associated editorial [2]. We congratulate the authors for their impressive series, thoughtful approach and excellent results. We would like to discuss the previously published alternative strategies for mild and normothermic total arch replacement. They demonstrate that an approach to bypass tailoring the degree of cooling to the anticipated extent of repair and duration of corporeal circulatory arrest can be rewarded with excellent outcomes [2]. Nonetheless, the authors had a mean circulatory arrest time of the lower body of 34 ± 12 min, extending to 70 min, at 30°C. These numbers are pushing the limits on warm ischaemia, as ‘safe’ ischaemic times are in the range of 35 min for the liver, 90 min for the kidneys and 20 min for the spinal cord [3] at mild hypoor normothermia. Furthermore, their approach required an elaborate succession of cannulations (up to four) and retrograde descending aorta perfusion (as well as a portion of the arch vessels at intermediate steps of completing the arch replacement) through the femoral artery. In a patient population burdened with atheromatous large vessel disease such as this one, this is not an innocuous choice devoid of risk compared with antegrade perfusion. Axillary artery cannulation has been shown to provide adequate antegrade cerebral perfusion, which we have been using routinely since 2001, including in patients with acute aortic dissection [4]. We have continued to apply this approach routinely since then, with comparable results. Total arch replacement is also possible under whole body antegrade perfusion [5], by placing a Medtronic DLP© venous cannula (Y-ed from the arterial line) through the tube graft into the distal aorta for antegrade lower body perfusion (see figure available at: http://ats.ctsnetjournals.org/content/vol85/issue1/ images/large/347.S0003497507013525.gr1.jpeg). The brain and lower body are continuously perfused with the exception of a very limited circulatory arrest time (6–8 min) of the lower body, which only represents the time necessary for resection of the aortic tissues, positioning of the cuffed DLP cannula in the descending aorta and the inflation of the occlusion balloon. In this way, an arch repair is transformed into a standard cardiopulmonary bypass heart operation, with vascular exclusion of the aortic arch and total body antegrade perfusion. The 8 min limited duration of the circulatory arrest in the lower body is safe for the spinal cord and splanchnic organs at this temperature and even in normothermia, as can be necessary in patients who cannot be cooled, such as with cold reactive agglutinins [6]. Furthermore, cannulation of the newly implanted graft is not necessary to achieve antegrade systemic perfusion after the completion of the distal aortic anastomosis. We would also like to note that we have applied this approach in emergent situations, such as acute aortic dissection, with good results, and not restricted this technique to elective cases as reported by Urbanski et al. [1].

A comprehensive study of autonomic dysfunction in the fibromyalgia patients

The hypothesis of autonomic nervous system involvement in pathophysiology in the patients with fibromyalgia has been addressed and tested time and again but the existing reports are both contradictory and inconclusive. A complete knowledge of the degree of autonomic dysfunction in fibromyalgia patients would be more substantial. We conducted a comprehensive non-invasive study to investigate the complete autonomic profile of female patients with fibromyalgia. An autonomic function test using a standard battery and heart rate variability analysis in the 42 fibromyalgia patients as well as 42 age matched healthy controls was performed. Both autonomic activity (tone) and reactivity were measured. Autonomic tone (both time and frequency domain parameters) was measured using heart rate variability (HRV) analysis. Autonomic reactivity was measured using a standard battery of autonomic function tests. Resting blood pressure (both systolic and diastolic) was significantly higher in the fibromyalgia patients than controls. The time domain variables and HF% as recorded by HRV were significantly lower in the patients than the controls. The autonomic reactivity for sympathetic and parasympathetic nervous system was found to be within normal limits. The cardiac autonomic function is normal and the autonomic reflex arc seems to be intact in the patients with fibromyalgia.

The acute effects of palonosetron on ECG parameters in patients with cancer.

e19693 Background: Serotonin receptor (5HT3) antagonists like dolasetron, ondansetron, granisetron and tropisetron have shown to cause QT prolongation. However, there is few data about palonosetron-related cardiac side effects. In this study, we aimed to determine the acute effects of palonosetron on QT interval, heart rate and arterial blood pressure. Methods: 101 cancer patients (51 female, 50 male) were enrolled to the study. Pts with acute ischemic heart disease and arrhythmia were excluded. Pts received 0.25 mg of palonosetron for prevention of chemotherapy-induced emesis. Standard 12-lead ECG recordings, heart rate (HR) and blood pressure (BP) measurements were performed at baseline, 30 minutes and 60 minutes after the palonosetron administration. By using Bazzet Formula, corrected QT interval (QTc) and QT dispersion (QTd) were calculated. Results: The mean age of pts was 54 ±13 years. In whole patient group, there were no differences in QTc, QTd measurements at 30 and 60 minutes after palonosetron injection when compared to baseline measurements. However, HR significantly decreased at 30 and 60 minutes after palonosetron injection. Compared with the baseline, systolic BP decreased nonsignificantly at 30 minute and then returned to baseline levels at 60 minute after palonosetron administration. When body surface area was taken into consideration, patients who received palonosetron over a dose of 0.13 mg/m2 had a decrease of QTc, HR and systolic BP at 30 minute and increase of these parameters at 60 minute. Conclusions: Palonosetron does not cause QT prolongation in standard doses, but causes a decrease in heart rate. Although there is no significant risk of QT prolongation with palonosetron, caution should be taken when QT prolonging drugs are used concomitantly and in patients with long QT syndrome. The routine administration of the drug at a fixed dose without any adjustment for body weight and body surface area can increase the risk of cardiac side effects in lean patients.

Relationships of night/day heart rate ratio with carotid intima media thickness and markers of arterial stiffness

Objectives To analyze the relationship between office and ambulatory heart rate, and its variability, and arterial stiffness in patients with primary arterial hypertension. Methods A cross-sectional study was conducted in a primary care setting, with the inclusion of 356 hypertensive patients aged 30–80 years. Office and ambulatory blood pressure, heart rate, night/day heart rate ratio and the corresponding standard deviations, were determined. Arterial stiffness was assessed according to carotid intima media thickness, pulse wave velocity, the central and peripheral augmentation index, and the ambulatory arterial stiffness index. Results Carotid intima media thickness, central and peripheral augmentation index, and ambulatory arterial stiffness index were negatively correlated to office and ambulatory heart rate and its standard deviation, and positively correlated to the night/day heart rate ratio. Pulse wave velocity showed a negative correlation to 24 h standard deviation heart rate and a positive correlation to nocturnal heart rate and the night/day heart rate ratio. For each 10 bpm increment in 24 h heart rate, the pulse wave velocity increased 0.42 m/s (95%CI: 0.23–0.60) and ambulatory arterial stiffness index decreased 0.01 (95%CI: 0.01–0.02); in the case of office heart rate, the peripheral augmentation index decreased 4.74 (95%CI: 3.15–6.33) and central augmentation index decreased 3.52 (95%CI: 2.43–4.30), while for 24 h standard deviation heart rate, carotid intima media thickness decreased 0.03 mm (95%CI: 0.01–0.06). Conclusions Office and ambulatory heart rate, and the corresponding standard deviations, are inversely associated to the arterial stiffness markers, with the exception of pulse wave velocity, where a direct correlation is observed. A greater increase in night/day ratio, i.e., a lesser decrease in nocturnal heart rate, is associated to increased arterial stiffness.

Palmitate-Induced Translocation of Caveolin-3 and Endothelial Nitric Oxide Synthase in Cardiomyocytes

PROBLEM STATEMENT: Palmitate is a known cardiac lipotoxin that blunts cardiomyocyte contractile function and induces apoptosis, likely via accumulation of the lipotoxic ceramide. Ceramide is a sphingolipid and localizes to caveolae, which are lined in the inner membrane leaflet by caveolin proteins. In this study, we investigated the effects of palmitate on caveolin proteins and on endothelial Nitric Oxide Synthase (eNOS), a signaling mediator that binds to caveolin-3, the muscle-specific caveolae scaffolding protein. APPROACH AND RESULTS: Mice fed a high palmitate diet for 12 weeks showed pathologically increased coronary flow in the ex vivo Langendorff heart especially at low extracellular calcium concentrations. In these hearts, eNOS Ser1177 phosphorylation was increased compared to standard or high fat control diet hearts. This suggested that eNOS, a potent vasodilator in the heart, is affected by palmitate. In vitro experiments showed that exposure of HL-1 cardiomyocytes to palmitate causes translocation of eNOS from the plasma membrane to a perinuclear location and causes an 80% decrease in Thr495 phosphorylation. This corresponded with a 41% decrease in NO production. To determine the mechanism of the loss of plasma membrane bound eNOS, we investigated the effect of palmitate on caveolin-3 and found decreased caveolin-3 protein levels by 70% compared to control cells. The remaining 30% of caveolin-3 was localized to a perinuclear location. In contrast to previous studies, palmitate did not cause apoptosis in cardiomyocytes. CONCLUSION: Overall, we show for the first time that a high palmitate diet leads to loss of caveolin-3 in cardiomyocytes and to coronary dysfunction of the mouse heart, via uncoupling of eNOS.

Discrimination power of long-term heart rate variability measures for chronic heart failure detection

The aim of this study was to investigate the discrimination power of standard long-term heart rate variability (HRV) measures for the diagnosis of chronic heart failure (CHF). The authors performed a retrospective analysis on four public Holter databases, analyzing the data of 72 normal subjects and 44 patients suffering from CHF. To assess the discrimination power of HRV measures, an exhaustive search of all possible combinations of HRV measures was adopted and classifiers based on Classification and Regression Tree (CART) method was developed, which is a non-parametric statistical technique. It was found that the best combination of features is: Total spectral power of all NN intervals up to 0.4 Hz (TOTPWR), square root of the mean of the sum of the squares of differences between adjacent NN intervals (RMSSD) and standard deviation of the averages of NN intervals in all 5-min segments of a 24-h recording (SDANN). The classifiers based on this combination achieved a specificity rate and a sensitivity rate of 100.00 and 89.74%, respectively. The results are comparable with other similar studies, but the method used is particularly valuable because it provides an easy to understand description of classification procedures, in terms of intelligible "if … then …" rules. Finally, the rules obtained by CART are consistent with previous clinical studies.

Ethnic and Gender Differences in the Relationship Between Hostility and Metabolic and Autonomic Risk Factors for Coronary Heart Disease

To examine the relationship between hostility and biological risk factors for coronary heart disease (CHD) in a population of white European and South Asian men and women living in the United Kingdom. This cross-sectional study involved a community-based sample of 1,757 healthy white and South Asian men and women aged between 35 years and 75 years from West London. Participants completed the Cook-Medley Hostility Scale, together with measures of standard biological risk factors and heart rate variability. Associations between hostility and CHD risk factors were evaluated, controlling for age, education, smoking, physical activity, body mass index, and waist/hip ratio, using regression models. In white men, hostility was associated positively with fasting glucose, glycosylated hemoglobin, and negatively with high-density lipoprotein cholesterol. High levels of hostility were also related to increased prevalence of diabetes and the metabolic syndrome in white men. Hostility in South Asian men was associated with impaired autonomic function. Hostility was not related to any biological CHD risk factors in South Asian or white women. Our results showed that hostility was independently associated with glucose metabolism and dyslipidemia in white men, and with autonomic dysfunction in South Asian men. Hostility was found not to be relevant for measured CHD risk factors in females. Longitudinal data are required to establish whether the impact of hostility on CHD risk in men is mediated through metabolic and autonomic processes.

The normal ranges of cardiovascular parameters in children measured using the Ultrasonic Cardiac Output Monitor

The Ultrasonic Cardiac Output Monitor is a noninvasive method of hemodynamic assessment and monitoring in critically ill patients. There are no published reference ranges for normal values in children for this device. This study aimed to establish normal ranges for cardiovascular indices measured using Ultrasonic Cardiac Output Monitor in children aged 0-12 yrs old and to assess interobserver reliability. This was a population-based cross-sectional observational study. Schools and kindergartens in Hong Kong. Chinese children aged up to 12 yrs old. Two operators performed Ultrasonic Cardiac Output Monitor scans on each child together with standard oscillometric measurement of blood pressure and heart rate. Software intrinsic to the Ultrasonic Cardiac Output Monitor device produces values for stroke volume, cardiac output, and systemic vascular resistance. For each parameter, normal ranges were defined as lying between the 2.5th and 97.5th percentiles. Interobserver reliability was assessed with Bland-Altman plots, coefficients of variation, and intraclass correlation. A total of 1,197 Chinese children (55% boys) were scanned. Normal ranges of values for cardiac output, stroke volume, and systemic vascular resistance indices are presented. Interobserver reliability for Ultrasonic Cardiac Output Monitor was superior to that for standard blood pressure and heart rate measurement. This large study presents normal values for cardiovascular indices in children using the Ultrasonic Cardiac Output Monitor with good interobserver reliability.