Long-term Heart Research Articles

Graft-Infiltrating Macrophages Adopt an M2 Phenotype and Are Inhibited by Purinergic Receptor P2X7 Antagonist in Chronic Rejection.

Macrophages exhibit diverse phenotypes and functions; they are also a major cell type infiltrating chronically rejected allografts. The exact phenotypes and roles of macrophages in chronic graft loss remain poorly defined. In the present study, we used a mouse heart transplant model to examine macrophages in chronic allograft rejection. We found that treatment of C57BL/6 mice with CTLA4 immunoglobulin fusion protein (CTLA4-Ig) prevented acute rejection of a Balb/c heart allograft but allowed chronic rejection to develop over time, characterized by prominent neointima formation in the graft. There was extensive macrophage infiltration in the chronically rejected allografts, and the graft-infiltrating macrophages expressed markers associated with M2 cells but not M1 cells. In an in vitro system in which macrophages were polarized into either M1 or M2 cells, we screened phenotypic differences between M1 and M2 cells and identified purinergic receptor P2X7 (P2x7r), an adenosine triphosphate (ATP)-gated ion channel protein that was preferentially expressed by M2 cells. We further showed that blocking the P2x7r using oxidized ATP (oATP) inhibited M2 induction in a dose-dependent fashion in vitro. Moreover, treatment of C57BL/6 recipients with the P2x7r antagonist oATP, in addition to CTLA4-Ig treatment, inhibited graft-infiltrating M2 cells, prevented transplant vasculopathy, and induced long-term heart allografts survival. These findings highlight the importance of the P2x7r-M2 axis in chronic rejection and establish P2x7r as a potential therapeutic target in suppression of chronic rejection.

Long-term Coarse Particulate Matter Exposure and Heart Rate Variability in the Multi-ethnic Study of Atherosclerosis.

Reduced heart rate variability, a marker of impaired cardiac autonomic function, has been linked to short-term exposure to airborne particles. This research adds to the literature by examining associations with long-term exposures to coarse particles (PM10-2.5). Using electrocardiogram recordings from 2,780 participants (45-84 years) from three Multi-ethnic Study of Atherosclerosis sites, we assessed the standard deviation of normal to normal intervals and root-mean square differences of successive normal to normal intervals at a baseline (2000-2002) and follow-up (2010-2012) examination (mean visits/person = 1.5). Annual average concentrations of PM10-2.5 mass, copper, zinc, phosphorus, silicon, and endotoxin were estimated using site-specific spatial prediction models. We assessed associations for baseline heart rate variability and rate of change in heart rate variability over time using multivariable mixed models adjusted for time, sociodemographic, lifestyle, health, and neighborhood confounders, including copollutants. In our primary models adjusted for demographic and lifestyle factors and site, PM10-2.5 mass was associated with 1.0% (95% confidence interval [CI]: -4.1, 2.1%) lower standard deviation of normal to normal interval levels per interquartile range of 2 μg/m. Stronger associations, however, were observed before site adjustment and with increasing residential stability. Similar patterns were found for root-mean square differences of successive normal to normal intervals. We found little evidence for associations with other chemical species and with the rate of change in heart rate variability, though endotoxin was associated with increasing heart rate variability over time. We found only weak evidence that long-term PM10-2.5 exposures are associated with lowered heart rate variability. Stronger associations among residentially stable individuals suggest that confirmatory studies are needed.

Development and validation of cardiovascular risk scores for haemodialysis patients

BackgroundA simple clinical tool to predict cardiovascular disease risk does not exist for haemodialysis patients. The long-term coronary risk Framingham Heart Study Risk score (FRS), although used in this population, may be inadequate. Therefore, we developed separate risk-scores for cardiovascular mortality (CVM) and cardiovascular morbidity & mortality (CVMM) in a Fresenius Medical Care-based haemodialysis patient cohort (AROii). MethodsApplying a modified FRS approach, we derived and internally validated two-year risk-scores in incident European adult patients randomly assigned to a development (N=4831) or a validation (N=4796) dataset. External validation was conducted in the third Dialysis Outcomes and Practice Patterns Study (DOPPS III) cohort. Additional discrimination comparing to the FRS was performed. ResultsThe overall two-year CVM and CVMM event rates were 5.0 and 22.6 per 100 person-years respectively. Common risk predictors included increasing age, cardiovascular disease history, primary diabetic nephropathy, low blood pressure, and inflammation. The CVM score was more predictive in AROii (c-statistic 0.72) and in DOPPS III (c-statistic 0.73–0.74) than the CVMM score (c-statistic 0.66–0.67 & 0.63 respectively). The FRS was not predictive of either CVM (c-statistic 0.54) or CVMM (c-statistic 0.56) in AROii. ConclusionsWe describe novel, easy-to-apply and interpret CV risk-scores for haemodialysis patients. Our improved cardiovascular prediction performance over traditional (FRS) scores reflected its tailored development and validation in haemodialysis populations, and the integration of non-classical cardiovascular risk factors. The lower expected versus observed CVM and CVMM risk suggests the existence of novel cardiovascular risk factors in this patient population not measured in this study.

Visualization of Heart Rate Variability of Long-Term Heart Transplant Patient by Transition Networks: A Case Report.

We present a heart transplant patient at his 17th year of uncomplicated follow-up. Within a frame of routine check out several tests were performed. With such a long and uneventful follow-up some degree of graft reinnervation could be anticipated. However, the patient's electrocardiogram and exercise parameters seemed largely inconclusive in this regard. The exercise heart rate dynamics were suggestive of only mild, if any parasympathetic reinnervation of the graft with persisting sympathetic activation. On the other hand, traditional heart rate variability (HRV) indices were inadequately high, due to erratic rhythm resulting from interference of the persisting recipient sinus node or non-conducted atrial parasystole. New tools, originated from network representation of time series, by visualization short-term dynamical patterns, provided a method to discern HRV increase due to reinnervation from other reasons.

Phonocardiogram signal compression using sound repetition and vector quantization

BackgroundA phonocardiogram (PCG) signal can be recorded for long-term heart monitoring. A huge amount of data is produced if the time of a recording is as long as days or weeks. It is necessary to compress the PCG signal to reduce storage space in a record and play system. In another situation, the PCG signal is transmitted to a remote health care center for automatic analysis in telemedicine. Compression of the PCG signal in that situation is necessary as a means for reducing the amount of data to be transmitted. Since heart beats are of a cyclical nature, compression can make use of the similarities in adjacent cycles by eliminating repetitive elements as redundant. This study proposes a new compression method that takes advantage of these repetitions. MethodsData compression proceeds in two stages, a training stage followed by the compression as such. In the training stage, a section of the PCG signal is selected and its sounds and murmurs (if any) decomposed into time–frequency components. Basic components are extracted from these by clustering and collected to form a dictionary that allows the generative reconstruction and retrieval of any heart sound or murmur. In the compression stage, the heart sounds and murmurs are reconstructed from the basic components stored in the dictionary. Compression is made possible because only the times of occurrence and the dictionary indices of the basic components need to be stored, which greatly reduces the number of bits required to represent heart sounds and murmurs. The residual that cannot be reconstructed in this manner appears as a random sequence and is further compressed by vector quantization. What we propose are quick search parameters for this vector quantization. ResultsFor normal PCG signals the compression ratio ranges from 20 to 149, for signals with median murmurs it ranges from 14 to 35, and for those with heavy murmurs, from 8 to 20, subject to a degree of distortion of ~5% (in percent root-mean-square difference) and a sampling frequency of 4kHz. DiscussionWe discuss the selection of the training signal and the contribution of vector quantization. Performance comparisons between the method proposed in this study and existing methods are conducted by computer simulations. ConclusionsWhen recording and compressing cyclical sounds, any repetitive components can be removed as redundant. The redundancies in the residual can be reduced by vector quantization. The method proposed in this study achieves a better performance than existing methods.

An Implantable Pressure Sensor for Long-term Wireless Monitoring of Cardiac Function -First Study in Man

Background: Heart failure is a huge health problem. The possibility of long-term monitoring heart function more accurately in these patients has gained increasing interest. The primary aim of this study was to see if a wireless pressure sensor can be safely implanted to give accurate and reproducible long-term intracardiac pressure recordings. Another aim was to see if there are any adverse effects connected with the implant. A control group was included for comparison of clinical data. Methods: Forty patients with heart failure, 31 scheduled for open heart surgery and 9 for transcatheter aortic valve replacement (TAVR) were included to test the safety and feasibility of the Titan™ pressure sensor. The patients were randomized to the implant or control group. Findings: Initial sensor measurements showed very good correlation with reference pressure values from a fluid-filled catheter, and there was no need for calibration of the sensor. At the 6-month follow-up 11 patients had been wearing the implant for >1 year with a median time of 560 days. Ten of these had adequate sensor function. Compared to the control group there was no difference in adverse clinical events and the overall number of complications was low. Conclusions: This first study in man on a new implantable wireless hemodynamic monitor showed favorable results regarding our primary endpoints; accuracy of recordings over time and safety profile. The technology has great potential for monitoring at home since it is easy to use in the out-patient setting.

T Cell Response in Patients with Implanted Biological and Mechanical Prosthetic Heart Valves.

The study was aimed at assessing T cell subsets of peripheral blood from recipients of long-term functioning (more than 60 months) biological and mechanical heart valve prostheses. The absolute and relative number of CD4 and CD8 T cell subsets was analyzed: naïve (N, CD45RA+CD62L+), central memory (CM, CD45RA−CD62L+), effector memory (EM, CD45RA−CD62L−), and terminally differentiated CD45RA-positive effector memory (TEMRA, CD45RA+CD62L−) in 25 persons with biological and 7 with mechanical prosthesis compared with 48 apparently healthy volunteers. The relative and absolute number of central memory and naïve CD3+CD8+ in patients with biological prosthesis was decreased (p < 0.001). Meanwhile the number of CD45RA+CD62L−CD3+CD8+ and CD3+CD4+ was increased (p < 0.001). Patients with mechanical prosthesis had increased absolute and relative number of CD45RA+CD62L−CD3+CD8+ cells (p = 0.006). Also the relative number of CD3+CD4+ cells was reduced (p = 0.04). We assume that altered composition of T cell subsets points at development of xenograft rejection reaction against both mechanical and biological heart valve prostheses.

0008: Cardiogenic shock and Impella 5.0

Cardiogenic shock is associated with a high mortality rate. Mechanical circulatory supports have been developed for refractory cardiogenic shock. The Impella 5.0 device is a rotary microaxial pump mounted on a catheter across the aortic valve, minimally invasively placed, designed for short-term circulatory support, and providing left ventricular unloading. All patients admitted in our cardiac intensive care for acute refractory cardiogenic shock and treated with Impella 5.0 between January 2010 and January 2015 were included. 12 patients were enrolled. The causes of cardiogenic shock and indications for using Impella device were acute myocardial infarction for 6 (50%), decompensated dilated cardiomyopathy for 4 (34%), myocarditis for 1 (8%) and cardiac surgery for 1 (8%). The mean duration of support was 13±8 days. The 30-days and 1-year survival was respectively 75% and 58%. Among 30-days survivors, ventricular function recovered in 5 (56%), 3 (33%) underwent heart transplant and 1 (11%) underwent implantation of a Heartmate II. Our outcomes demonstrate that the use of the Impella 5.0 strongly improved survival at 6 months. Myocardial recovery was achieved in most patients. The Impella also allowed safe implantation of long-term assistance and successful heart transplantation. Abstract 0008 – Table IMPELLA 5.0 Left ventricular ejection function (%) 21±6 Right ventricular dysfunction n (%) 0 (0) Cardiac index (L/min/m 2 ) 1.3±0.2 Mean arterial pressure (mmHg) 66±9 Systolic blood pressure (mmHg) 89±13 Lactates (mmol/L) 6.5±5 Duration of support (days) 14±8 Duration of hospitalisation in intensive care (days) 39±15 30-days survival n (%) 8 (73) 6-months survival n (%) 7 (64) 1-month LEVF (%) 45±9 Myocardial recovery n (%) 4 (63) Heart transplant (n (%) 3 (11) LVAD (Heartmate 2) n (%) 1 (9)

Optimal facial areas for webcam-based photoplethysmography

For long-term pulse tracking, it is possible to use the photoplethysmography method, the essence of which is estimating the dynamics of optical properties of examined organ tissues. Since this method is not invasive and does not need complicated equipment, it can be used for long-term heart rate monitoring in a wide range of operating conditions. In several publications, it is shown that different variations of this method can be used for estimating the heart rate by means of a web camera shooting a face. Image analysis procedures are used for estimating the time dynamics of optical properties of local fragments of the epidermis. In the present work, we examine a problem on determining facial areas most suitable for pulse detecting. The ViolaJones algorithm is used for detecting facial areas. Coordinates of several regions where the color signal is measured are calculated with respect to the detected face. The color signal characterizes variation of color components for images of the epidermis. For estimating whether the image area is optimal, the corresponding criterion that characterizes the degree of frequency manifestation in the color signal spectrum close to the real value of heart rate is formulated. According to this criterion, the optimal regions are determined and they are as follows: the area near the nose and the area on the nose between the eyes.

Altered Adipocytokine Levels and Heart Rate Variability in Schizophrenic Patients with Risk of Metabolic Syndrome.

The aim of this study was to investigate changes in the levels of high-sensitivity C-reactive protein (Hs-CRP), tumor necrosis factor α (TNF-α), myocardial fibrosis, and long-term heart rate variability (HRV) in schizophrenic patients at risk of developing metabolic syndrome (MS). 45 subjects without schizophrenia or MS were recruited into the control group (group A), 45 schizophrenic patients not at risk for developing MS constituted group B, and 45 schizophrenic patients at risk of MS constituted group C. Serum levels of TNF-α and Hs-CRP were examined by enzyme linked immunosorbent assay (ELISA). Ultrasonic acoustic densitometry (AD) analysis was performed to assess myocardial fibrosis, and 24 hours dynamic electrocardiography was conducted to determine HRV time-domain index. Compared with the control group, schizophrenic patients at risk of MS displayed a reduced HRV (p < 0.05). The AD parameter CAI increased in schizophrenic patients with MS risk as compared to the control group (p < 0.05), whereas CVIB was significantly lowered (p > 0.05). Moreover, serum levels of TNF-α and Hs-CRP in the schizophrenic patients with MS risk were elevated compared with the control group (p <0.05). Due to the influence of such factors as high glucose levels, hypertension and obesity, schizophrenic patients at risk of MS exhibited elevated levels of TNF-α and Hs-CRP, enhanced ventricular myocardial fibrosis, and reduced HRV, which might have resulted from structural changes and autonomic nervous dysfunction in cardiac tissues.

Cardiorespiratory responses in an Antarctic fish suggest limited capacity for thermal acclimation.

Polar fishes are at high risk from increasing seawater temperatures. Characterising the physiological responses to such changes may both clarify mechanisms that permit life under extreme conditions and identify limitations in the response to continued global warming. We hypothesised that Notothenia coriiceps would show physiological compensation after an acute exposure to 5°C, and following 6 weeks warm acclimation, compared with ambient temperature (0°C). However, initial tachycardia (22.4±2.8 versus 12.8±1.1 min(-1); P<0.01) was not reversed by acclimation (21.0±1.9 min(-1)). Hyperventilation (45.5±3.1 versus 21.4±2.4 breaths min(-1); P<0.001) showed a modest reduction following acclimation (38.0±2.9 min(-1); P<0.05), while resting oxygen consumption (0.52±0.08 mmol kg(-1)h(-1)) was acutely increased at 5°C (1.07±0.10 mmol kg(-1)h(-1); P<0.001) but unchanged with acclimation. Autonomic blockade showed initial responses were mainly of vagal origin, with little subsequent withdrawal or recovery in long-term heart rate variability after 6 weeks. Given the limited cardiorespiratory capacity to withstand sustained warming, effective physiological compensation probably requires a more prolonged acclimation period.

Intrinsic cardiovascular autonomic regulatory system of astronauts exposed long-term to microgravity in space: observational study

The fractal scaling of the long-term heart rate variability (HRV) reflects the ‘intrinsic’ autonomic regulatory system. Herein, we examine how microgravity on the ISS affected the power-law scaling β (beta) of astronauts during a long-duration (about 6 months) spaceflight. Ambulatory electrocardiographic (ECG) monitoring was performed on seven healthy astronauts (5 men, 52.0±4.2 years of age) five times: before launch, 24±5 (F01) and 73±5 (F02) days after launch, 15±5 days before return (F03), and after return to Earth. The power-law scaling β was calculated as the slope of the regression line of the power density of the MEM spectrum versus frequency plotted on a log10–log10 scale in the range of 0.0001–0.01 Hz (corresponding to periods of 2.8 h to 1.6 min). β was less negative in space (−0.949±0.061) than on Earth (−1.163±0.075; P<0.025). The difference was more pronounced during the awake than during the rest/sleep span. The circadian amplitude and acrophase (phase of maximum) of β did not differ in space as compared with Earth. An effect of microgravity was detected within 1 month (F01) in space and continued throughout the spaceflight. The intrinsic autonomic regulatory system that protects life under serious environmental conditions on Earth is altered in the microgravity environment, with no change over the 6-month spaceflight. It is thus important to find a way to improve conditions in space and/or in terms of human physiology, not to compromise the intrinsic autonomic regulatory system now that plans are being made to inhabit another planet in the near future.

Riesgo cardiovascular a largo plazo tras un síndrome coronario agudo, todavía un reto

Growth Differentiation Factor-15 (GDF-15) predicts death and cardiovascular events in acute coronary syndromes (ACS). We aimed to assess the long-term prognostic value of GDF-15 in ACS.We included 358 patients with ACS who underwent coronary angiography. Plasma GDF-15 was measured and clinical data and long-term events were registered. Incremental value of GDF-15 for prognosing all-cause death above a clinical model including GRACE score, left ventricular ejection fraction <40%, prior myocardial infarction and age was assessed.GDF-15 concentrations >1800 ng/L were associated with an increased prevalence of cardiovascular risk factors. During 6.5 years of follow-up 56 patients died, 7 had values of GDF-15 < 1200 ng/L, 7 between 1200 and 1800 ng/L and 42 > 1800 ng/L. After adjustment for potential confounders, GDF-15 > 1800 ng/L were independently associated with all-cause death (HR 4.09; 95% CI 1.57–10.71; p = .004) and the composite of major adverse cardiovascular events (MACE) (HR 2.48; 95% CI 1.41–4.34; p = .001). For long-term all-cause death a significant increase of ROC curve was seen after addition of GDF-15 to a clinical model 0.876 (95% CI 0.823–0.928; p = .014). Same improvements were found for net reclassification improvement (0.776; 95% CI 0.494–1.037; p < .001) and integrated discrimination improvement (0.112; 95% CI 0.055–0.169; p < .001). Multivariate competing risk model showed a significant association between GDF-15 > 1800 ng/L and the incidence of heart failure but not of myocardial infarction.In the setting of ACS, GDF-15 is associated with long-term all-cause death, MACE and heart failure and provides incremental prognostic value beyond traditional risks factor.

Abstract 19544: The Familial Hypercholesterolemia Phenotype in the United States is Associated With an Age-dependent Increase in Long-term Coronary Heart Disease Risk

Introduction: Heterozygous familial hypercholesterolemia (FH) has an estimated prevalence of 1:200-500, affecting up to 1,500,000 individuals in the US. Available CHD risk prediction equations do not account for lifetime exposure to elevated LDL-C in FH patients, and while relative risks of 7-100 have been reported for CHD in FH, US outcomes of FH are unknown. We aimed to evaluate long-term CHD risk in US adults with an FH phenotype. Methods: Using pooled data from 6 US epidemiologic cohorts, participants were stratified by LDL-C level at index ages 25, 35, 45, 55, 65 and 75 years. LDL-C≥190 and &lt;130 mg/dL defined the FH phenotype and referent groups, respectively. We used Cox regression models to assess covariate-adjusted associations of the FH phenotype with the hazard for fatal/nonfatal MI and CHD death and to generate 30-year event-free survival curves. Results: A total of 42,390 baseline person-exams were available across the index ages. The table shows the 30-year event rates for patients with the FH phenotype (LDL-C≥190 mg/dL) compared with the referent from each index age, as well as covariate-adjusted HRs for CHD death or fatal/nonfatal MI. As expected, the relative increase in 30-year events is highest for the youngest individuals, with rates up to 12 times higher for CHD death, and attenuates at older index ages. After adjustment, HRs for both CHD death and fatal/nonfatal MI are more modest but show a similar age-dependent pattern. The figure shows the adjusted 30-year survival free of fatal/nonfatal MI for the youngest two index ages, by LDL-C stratum. Conclusions: In the US, the FH phenotype is associated with substantial long-term CHD risk in younger adults, with more modest elevations in risk at older ages. The absolute HRs are lower than previously described, possibly due to unique features in the US population, improved management compared to other historical cohorts, or misclassification of some participants who did not have longstanding high LDL-C.

Exposure to sub-chronic and long-term particulate air pollution and heart rate variability in an elderly cohort: the Normative Aging Study.

BackgroundShort-term particulate air pollution exposure is associated with reduced heart rate variability (HRV), a risk factor for cardiovascular morbidity and mortality, in many studies. Associations with sub-chronic or long-term exposures, however, have been sparsely investigated. We evaluated the effect of fine particulate matter (PM2.5) and black carbon (BC) exposures on HRV in an elderly cohort: the Normative Aging Study.MethodsWe measured power in high frequency (HF) and low frequency (LF), standard deviation of normal-to-normal intervals (SDNN), and the LF:HF ratio among participants from the Greater Boston area. Residential BC exposures for 540 men (1161 study visits, 2000–2011) were estimated using a spatio-temporal land use regression model, and residential PM2.5 exposures for 475 men (992 visits, 2003–2011) were modeled using a hybrid satellite based and land-use model. We evaluated associations between moving averages of sub-chronic (3–84 day) and long-term (1 year) pollutant exposure estimates and HRV parameters using linear mixed models.ResultsOne-standard deviation increases in sub-chronic, but not long-term, BC were associated with reduced HF, LF, and SDNN and an increased LF:HF ratio (e.g., 28 day BC: −2.3 % HF [95 % CI:−4.6, −0.02]). Sub-chronic and long-term PM2.5 showed evidence of relations to an increased LF and LF:HF ratio (e.g., 1 year PM: 21.0 % LF:HF [8.6, 34.8]), but not to HF or SDNN, though the effect estimates were very imprecise and mostly spanned the null.ConclusionsWe observed some evidence of a relation between longer-term BC and PM2.5 exposures and changes in HRV in an elderly cohort. While previous studies focused on short-term air pollution exposures, our results suggest that longer-term exposures may influence cardiac autonomic function.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-015-0074-z) contains supplementary material, which is available to authorized users.

Long-term smoking cessation and heart rate dynamics in an aging healthy cohort: Is it possible to fully recover?

AimTo evaluate the long-term influence of smoking cessation on the regulation of the autonomic cardiovascular system in an aging general population, using the subpopulation of lifelong non-smokers as control group. MethodsWe analyzed 1481 participants aged ≥50 years from the SAPALDIA cohort. In each participant, heart rate variability and heart rate dynamics were characterized by means of various quantitative analyzes of the inter-beat interval time series generated from 24-hour electrocardiogram recordings. Each parameter obtained was then used as the outcome variable in multivariable linear regression models in order to evaluate the association with smoking status and time elapsed since smoking cessation. The models were adjusted for known confounding factors and stratified by the time elapsed since smoking cessation. ResultsOur findings indicate that smoking triggers adverse changes in the regulation of the cardiovascular system, even at low levels of exposure since current light smokers exhibited significant changes as compared to lifelong non-smokers. Moreover, there was evidence for a dose–response effect. Indeed, the changes observed in current heavy smokers were more marked as compared to current light smokers. Furthermore, full recovery was achieved in former smokers (i.e., normalization to the level of lifelong non-smokers). However, while light smokers fully recovered within the 15 first years of cessation, heavy former smokers might need up to 15–25 years to fully recover. ConclusionThis study supports the substantial benefits of smoking cessation, but also warns of important long-term alterations caused by heavy smoking.

Short- and Long-Term Heart Transplant Recipient Outcomes Are Adversely Affected by Donor pH

Short- and Long-Term Heart Transplant Recipient Outcomes Are Adversely Affected by Donor pH

The Registry of the International Society for Heart and Lung Transplantation: Eighteenth Official Pediatric Heart Transplantation Report—2015; Focus Theme: Early Graft Failure

The Registry of the International Society for Heart and Lung Transplantation: Eighteenth Official Pediatric Heart Transplantation Report—2015; Focus Theme: Early Graft Failure

Generalized discriminant analysis for congestive heart failure risk assessment based on long-term heart rate variability

The aims of this study are summarized in the following items: first, to investigate the class discrimination power of long-term heart rate variability (HRV) features for risk assessment in patients suffering from congestive heart failure (CHF); second, to introduce the most discriminative features of HRV to discriminate low risk patients (LRPs) and high risk patients (HRPs), and third, to examine the influence of feature dimension reduction in order to achieve desired accuracy of the classification. We analyzed two public Holter databases: 12 data of patients suffering from mild CHF (NYHA class I and II), labeled as LRPs and 32 data of patients suffering from severe CHF (NYHA class III and IV), labeled as HRPs. A K-nearest neighbor classifier was used to evaluate the performance of feature set in the classification. Moreover, to reduce the number of features as well as the overlap of the samples of two classes in feature space, we used generalized discriminant analysis (GDA) as a feature extraction method. By applying GDA to the discriminative nonlinear features, we achieved sensitivity and specificity of 100% having the least number of features. Finally, the results were compared with other similar conducted studies regarding the performance of feature selection procedure and classifier besides the number of features used in training.

Abstract 129: Inhibition of MEF2 By Atenolol Modifies the Transcriptome During Cardiac Hypertrophy to Improve Heart Function

Cardiac hypertrophy is a growth response of the adult heart that often results from increased mechanical loading due to high blood pressure and myocardial damage caused by ischemic heart disease. The β1 selective β-adrenergic antagonist, atenolol, is historically one of the most frequently prescribed of all medicines used to preserve heart function following myocardial damage. Transcription factor, myocyte enhancer factor 2 (MEF2), is required for early cardiac development and has also been implicated in cardiac hypertrophy. The effect of β-blockade on the gene program that is activated following cardiac hypertrophy as heart failure progresses is not fully understood. Here we show that treatment with atenolol leads to in vivo changes within the murine heart to reverse cardiac hypertrophy, and this is accompanied by repression of MEF2 activity. Cardiac hypertrophy was simulated using transverse aortic constriction (TAC) for four weeks in a transgenic MEF2-lacZ mouse model, followed by six weeks of vehicle (AT-) or atenolol treatment (AT+). Physiological responses in cardiac function, fibrosis, and cardiomyocyte size in TAC+AT+ mice were consistent with cardiac hypertrophy and demonstrated increased MEF2 activity compared to control (TAC-AT-). Atenolol treatment resulted in an overall improvement in cardiac function of TAC+ mice, showing a decrease in cardiomyocyte size, fibrosis and MEF2 activity. RNA was isolated from the left ventricle of the heart to determine changes in mRNA and lncRNA using RNA-seq. Atenolol reversed the expression of a specific subset of genes and lncRNA that become upregulated by TAC which corresponded to gene ontology terms related to metabolism and the immune system. Together, these data demonstrate that atenolol treatment during cardiac hypertrophy inhibits MEF2 activity and concomitantly leads to improved cardiac function. Thus, inhibition of MEF2 may be necessary to improve or reverse the effects of long-term heart failure.