Cardiac RR Research Articles

A 10-Year Nationwide Analysis of Risk Factors of Readmission and the Implications of Same-Day Discharge Following Velopharyngeal Insufficiency Correcting Surgery.

To investigate risk factors for readmission and the implications of same-day discharge for surgical management of velopharyngeal insufficiency (VPI). Retrospective cohort. Multi-institutional/national. Patients who underwent VPI-correcting surgery (n = 4479) were identified in the National Surgical Quality Improvement Program Pediatric database from 2012-2021. 30-day unplanned readmission. A total of 3878 (86.6%) patients were admitted inpatient following surgical intervention, while 601 (13.4%) were discharged on the same day. Thirty-day readmission rate was 1.7% across all patients. Based on multivariate logistic regression, patient factors identified as significant predictors of 30-day readmission included ASA class 4 (OR 11.22 [95% CI 1.01-124.91]; p = 0.049), steroid use (OR 7.30 [95% CI 2.22-23.97]; p = 0.001), and gastrointestinal disease (OR 2.48 [95% CI 1.22-5.00]; p = 0.012). Upon interaction analysis, patients with cardiac or neuromuscular disease who were discharged on the same day of surgery were associated with a higher readmission rate than those admitted to the hospital (cardiac disease RR 6.72 [95% CI 1.41-32.06]; p = 0.017) and (neuromuscular disease RR 12.39 [95% CI 1.64-93.59]; p = 0.015). Approximately 90% of VPI-correcting procedures are completed inpatient nationwide. Cardiac and/or neuromuscular disease significantly increased the patients' readmission risk when discharged on the same day of surgery. The inpatient setting should remain the best practice as adequate resources are available to mitigate life-threatening complications.

Reactivity of observers' facial skin blood flow depending on others' facial expressions and blushing.

Facial skin blood flow (SkBF) has attracted attention as an autonomic indicator because it influences facial colour, which informs others of emotional states, and facial temperature related to social anxiety. Previous studies have examined the facial SkBF in people experiencing emotions; however, facial SkBF changes in the observers of emotions are poorly understood. Our study clarified facial SkBF changes related to observing others' emotions by comparing the changes with other physiological indices. Thirty healthy participants (24 females; mean age: 22.17) observed six types of facial expressions (neutral, angry, and embarrassed expressions with and without facial blushing) and rated the emotional intensity of the other person. We measured their facial SkBF, finger SkBF, and cardiac RR interval as they made their observations. Facial SkBF generally decreased in relation to observing emotional faces (angry and embarrassed faces) and significantly decreased for angry expressions with blushing. None of the participants noticed blushing of facial stimuli. For the RR interval and finger SkBF, there was no variation depending on the observed facial expressions, although there was a general increase related to observation. These results indicated that facial SkBF is sensitive and reactive to emotional faces-especially angry faces with blushing- compared with other autonomic indices. The facial SkBF changes were not related to either RR interval changes or the intensity rating, suggesting that facial SkBF changes may be caused by vasoconstriction and have potential functions for our emotions. The decrease in facial SkBF may have a role in calming observers by preventing them from adopting the same emotional state as a person with intense anger. These findings clarify daily facial SkBF fluctuations and their relationship with our emotional processing in interpersonal situations.

Influence of physical fitness and weight status on autonomic cardiac modulation in children.

This study provides reference values for cardiovascular modulation at rest, during maximal exercise test and recovery after exercise in Caucasian children according to weight status and cardiorespiratory fitness (CRF)level. Additionally, the current study analyzed several correlations between autonomic cardiovascular modulation, cardiorespiratory performance and cardiometabolic risk. The principal goal of this study was to analyze cardiac function at rest, during maximum exercise, and during the recovery phase in children grouped according to weight status and CRFlevel. One hundred and fifty-two healthy children (78 girls) 10-16 years of age were divided into three groups: soccer and basketball players (SBG), endurance group (EG), and sedentary people with overweight and obesity (OOG). A cardiac RR interval monitor recorded the cardiac data and specific software analyzed the cardiac autonomic response through heart rate (HR) and HR variability. The study analyzed resting HR (RHR), HRpeak, and HR recovery (HRR). OOG showed significant poorer performance in the Léger test lower V̇O2 max and higher values of blood pressure at rest and post-exercise than sport groups. The EG presented the best results in CRF and cardiometabolic risk (CMR) in relation to SBG and OOG. The OOG showed higher percentage of HR values, compatible with an unhealthy cardiovascular autonomic modulation than the sport groups, with significant differences in bradycardia, HR reserve, and HRR 5 min. Aerobic performance, vagal activity, blood pressure, chronotropic competence, and HRR have significant associations with CMR parameters. The current study presents reference values of autonomic cardiac function in Caucasian children according to weight status and cardiorespiratory fitness level. Aerobic performance, vagal activity, blood pressure, chronotropic competence, and heart rate during the recovery period after exercise have significant associations with cardiometabolic risk parameters. Children with overweight and obesity show signs of autonomic dysfunction reflected as low cardiac vagal activity and poor chronotropic competence.

ASSOCIATION BETWEEN CARDIAC (PRO)RENIN RECEPTOR EXPRESSION AND MYOCARDIAL HYPERTROPHY IN HUMAN

Objective: The (pro)renin receptor [(P)RR] is expressed in vital organs throughout the body, with the highest expression level in the heart, and is thought to regulate the tissue renin-angiotensin system (RAS) through the non-proteolytic activation of prorenin. (P)RR is cleaved by processing enzymes to generate soluble (s)(P)RR, which is secreted into the extracellular space, and blood concentration of s(P)RR is considered to reflect the expression level of tissue RAS. Although it has been suggested that increased expression of (P)RR may be involved in cardiac pathophysiology in experimental studies, the significance of (P)RR expression in human heart remains unclear. Therefore, in the present studies, we investigated association between cardiac (P)RR expression and myocardial hypertrophy in human. Design and method: Study (1): We measured serum s(P)RR concentration and assessed the relationships between serum s(P)RR level and background factors including left ventricular mass index (LVMI) in 135 patients (57 males) of our department. Study (2): We performed immunostaining for (P)RR and atrial natriuretic peptide (ANP) and α-skeletal actin (SKA), markers for myocardial hypertrophy, in left ventricle specimens obtained from 13 autopsy cases. The expression level of (P)RR, ANP, or SKA and cardiomyocyte area were analyzed using an image processing software (ImageJ) and expression level of (P)RR was compared with cardiomyocyte area and expression level of ANP or SKA. Results: Study (1): The patients’ age was 57 (44–67) y.o., serum s(P)RR concentration was 22.8 (21.1–27.7) ng/ml, eGFR was 74.4 (59.4–91.2) ml/min/1.73 m2, and LVMI was 79 (66–90) g/ m2. Serum s(P)RR level was significantly positively correlated with LVMI (β = 0.238, p < 0.01) independent of other related factors. Study (2): (P)RR immunostaining was observed in cytoplasm of cardiomyocytes. The expression level of (P)RR was significantly positively correlated with cardiomyocyte area (ρ = 0.386, p < 0.001) and expression level of ANP (ρ = 0.782, p < 0.001) or SKA (ρ = 0.373, p < 0.001). Conclusions: These data suggested that cardiac (P)RR expression may be associated with myocardial hypertrophy in human. Further studies are needed to determine the underlying mechanism of this association.

Deep learning reconstruction for cardiac magnetic resonance fingerprinting T1 and T2 mapping.

To develop a deep learning method for rapidly reconstructing T1 and T2 maps from undersampled electrocardiogram (ECG) triggered cardiac magnetic resonance fingerprinting (cMRF) images. A neural network was developed that outputs T1 and T2 values when given a measured cMRF signal time course and cardiac RR interval times recorded by an ECG. Over 8 million cMRF signals, corresponding to 4000 random cardiac rhythms, were simulated for training. The training signals were corrupted by simulated k-space undersampling artifacts and random phase shifts to promote robust learning. The deep learning reconstruction was evaluated in Monte Carlo simulations for a variety of cardiac rhythms and compared with dictionary-based pattern matching in 58 healthy subjects at 1.5T. In simulations, the normalized root-mean-square error (nRMSE) for T1 was below 1% in myocardium, blood, and liver for all tested heart rates. For T2 , the nRMSE was below 4% for myocardium and liver and below 6% for blood for all heart rates. The difference in the mean myocardial T1 or T2 observed in vivo between dictionary matching and deep learning was 3.6 ms for T1 and -0.2 ms for T2 . Whereas dictionary generation and pattern matching required more than 4 min per slice, the deep learning reconstruction only required 336 ms. A neural network is introduced for reconstructing cMRF T1 and T2 maps directly from undersampled spiral images in under 400 ms and is robust to arbitrary cardiac rhythms, which paves the way for rapid online display of cMRF maps.

Average Entropy: Measurement of disorder for cardiac RR interval signals

We introduce average entropy (AE) as a disorder measure of heart rate time series. The AE measurement reflects both the probability distribution of all discrete values in a time series and the randomness of the series. The AE analysis is able to differentiate the congestive heart failure (CHF), the healthy, and the atrial fibrillation (AF) subjects for both short and long heart rate time series. The differentiation accuracy of AE is higher than 90%. In addition, since the meaning of “disorder” is easily confused with “complexity”, we explore the relation between them by analyzing heart rate time series. Specifically, we demonstrate that the complexity measured by entropy of entropy (EoE) versus the disorder measured by AE plot of heart rate time series exhibits a distinct inverted U relation.

20th Interventional Cardiology Workshop New Frontiers in Interventional Cardiology: December 12th, 2019, Krakow, Poland.

BackgroundIn recent years, the percentage of elderly patients has been increased, which means that this group of patients requires individualized treatment.AimTo assess the effectiveness of percutaneous coronary interventions (PCI) among seniors.Methods3188 of invasive procedures performed among patients over 75 years old in 2008–2013 met inclusion criteria. Demographical data, comorbidities, type and method of procedure were analyzed. Total mortality was estimated on 20.03.2018.ResultsIn the study group 79.5% of procedures were performed in stable coronary artery disease (CAD), 30.5% in acute coronary syndrome (ACS). Post-PCI stroke occurred in 0.9% of the subjects. Local complications were more frequent among women (4.3% vs. 1.6%, p < 0.001) and ACS group (4.4% vs. 1.8%, p < 0.001). In-hospital mortality rate was 5.4%. Risk factors increasing in-hospital mortality were: cardiac shock RR 0.95 (95% CI: 0.94–0.97), post-PCI creatinine level elevation RR 1.36 (95% CI: 1.03–1.77), and elevated INR RR – 1.57 (95% CI: 1.05–2.36). 10-year survival prognosis for post-PCI patients was 33.9%. Factors resulting in decreased long-term survival were: age RR = 1.07 (95% CI: 1.05–1.08), gender RR = 1.38 (95% CI: 1.23–1.57), prior ACS RR = 1.13 (95% CI: 1.01–1.29), kidney failure RR = 1.15 (95% CI: 1.03–1.28).ConclusionsPrognosis of seniors, who underwent PCI is good. After considering contraindications, invasive procedures in this group of patients should be performed both in stable CAD and ACS.

Assessment of dynamic characteristics of cardiac RR intervals during meditation using Poincaré plot and sequence trend analysis

Assessment of dynamic characteristics of cardiac RR intervals during meditation using Poincaré plot and sequence trend analysis

Aortic constriction induces hypertension and cardiac hypertrophy via (pro)renin receptor activation and the PLC‑β3 signaling pathway.

The (pro)renin receptor [(P)RR] serves an important role in cardiovascular complications. However, the precise mechanisms of (P)RR in the heart remain obscure. The authors hypothesized that overexpression of (P)RR would be associated with activation of the relevant signal pathway which could lead to organ injury. The aim of the present study was to test the role of cardiac (P)RR and its potential signaling pathway components including phospholipaseC(PLC), protein kinaseC(PKC), extracellular signal‑regulated kinase(ERK)1/2 and Raf‑1 proto‑oncogene, serine/threonine kinase(Raf‑1). Hypertension and cardiac hypertrophy were induced by partial abdominal aortic ligation in Sprague‑Dawley rats. The expression levels of cardiac (P)RR, PLC‑β3, PKC, ERK1/2 and Raf‑1 were measured following administration of the handle region peptide (HRP) and PLC‑β3 inhibitor U73122. The expression of (P)RR and PLC‑β3 significantly increased in the left ventricle (P<0.05). Levels of PKC‑α, ERK1/2 and Raf‑1 in the heart rose significantly (P<0.05). HRP and U73122 significantly decreased the levels of cardiac (P)RR and PLC‑β3. Furthermore, levels of PKC‑α, ERK1/2 and Raf‑1 were also decreased (P<0.05). Cardiac parameters, blood pressure and plasma Angiotensin(Ang)I and AngII levels were altered significantly (P<0.05). The results demonstrated that hypertension induced by aortic restriction activated the (P)RR in the heart. This action led to hypertension and cardiac hypertrophy via the (P)RR‑PLC‑β3‑PKC‑ERK1/2‑Raf‑1 signaling pathway. These results provide a mechanism by which elevated (P)RR levels in hypertension may contribute to the development of cardiac remodeling.

ADCY9 (Adenylate Cyclase Type 9) Inactivation Protects From Atherosclerosis Only in the Absence of CETP (Cholesteryl Ester Transfer Protein).

Pharmacogenomic studies have shown that ADCY9 genotype determines the effects of the CETP (cholesteryl ester transfer protein) inhibitor dalcetrapib on cardiovascular events and atherosclerosis imaging. The underlying mechanisms responsible for the interactions between ADCY9 and CETP activity have not yet been determined. Adcy9-inactivated ( Adcy9Gt/Gt) and wild-type (WT) mice, that were or not transgenic for the CETP gene (CETPtg Adcy9Gt/Gt and CETPtg Adcy9WT), were submitted to an atherogenic protocol (injection of an AAV8 [adeno-associated virus serotype 8] expressing a PCSK9 [proprotein convertase subtilisin/kexin type 9] gain-of-function variant and 0.75% cholesterol diet for 16 weeks). Atherosclerosis, vasorelaxation, telemetry, and adipose tissue magnetic resonance imaging were evaluated. Adcy9Gt/Gt mice had a 65% reduction in aortic atherosclerosis compared to WT ( P<0.01). CD68 (cluster of differentiation 68)-positive macrophage accumulation and proliferation in plaques were reduced in Adcy9Gt/Gt mice compared to WT animals ( P<0.05 for both). Femoral artery endothelial-dependent vasorelaxation was improved in Adcy9Gt/Gt mice (versus WT, P<0.01). Selective pharmacological blockade showed that the nitric oxide, cyclooxygenase, and endothelial-dependent hyperpolarization pathways were all responsible for the improvement of vasodilatation in Adcy9Gt/Gt ( P<0.01 for all). Aortic endothelium from Adcy9Gt/Gt mice allowed significantly less adhesion of splenocytes compared to WT ( P<0.05). Adcy9Gt/Gt mice gained more weight than WT with the atherogenic diet; this was associated with an increase in whole body adipose tissue volume ( P<0.01 for both). Feed efficiency was increased in Adcy9Gt/Gt compared to WT mice ( P<0.01), which was accompanied by prolonged cardiac RR interval ( P<0.05) and improved nocturnal heart rate variability ( P=0.0572). Adcy9 inactivation-induced effects on atherosclerosis, endothelial function, weight gain, adipose tissue volume, and feed efficiency were lost in CETPtg Adcy9Gt/Gt mice ( P>0.05 versus CETPtg Adcy9WT). Adcy9 inactivation protects against atherosclerosis, but only in the absence of CETP activity. This atheroprotection may be explained by decreased macrophage accumulation and proliferation in the arterial wall, and improved endothelial function and autonomic tone.

P13.04: Echo AV interval overestimates MCG PR interval in SSA+ pregnancies: evidence for new criteria for 1° AV block

We compared simultaneous fetal echo AV intervals (E-AV) and magentocardiogram (fMCG) PR intervals (M-PR) in SSA+ and control pregnancies to determine if an AV interval of + 2 z-scores correlated with a prolonged M-PR interval and 1° AV block. We searched the database of the University of Wisconsin Biomagnetism laboratory for pregnant women referred for fMCG with SSA antibodies. Maternal and pregnancy data were obtained from the mother's medical record. Fetal MCGs were performed using a 37-channel biomagnetometer (Magnes, 4D Neuroimaging, Inc). During the same session, we measured and averaged PR and cardiac RR intervals from 5 rhythm tracings and compared results to Echo Doppler AV interval (mitral inflow/aortic outflow) and RR intervals. Results were normalised for RR interval and compared by paired t-test. Regression analysis was used to test associations between gestational age (GA) and cardiac intervals. The mean M-PR was 23.3 ms less than the mean E-AV (95% CI: 20.1,26.5, p<0.001); this statistically significant difference persisted when normalised for RR interval. There were no significant differences between SSA and controls for RR, PR, or AV intervals. Neither E-RR interval or GA were associated with predicting E-AV; nor were M-RR or GA associated with predicting M-PR. However, the interaction between E-AV interval and GA were significantly associated with the AV-PR difference of 23.3 ms. Our results suggests that E-AV overestimates M-PR in both SSA and controls. Using the previous definition of 1° AVB (an AV interval of 150 ms) may result in unnecessary treatment of SSA+ normal fetuses. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Azilsartan attenuates cardiac damage caused by high salt intake through the downregulation of the cardiac (pro)renin receptor and its downstream signals in spontaneously hypertensive rats.

We examined whether the stimulation of the angiotensin II AT1 receptor increases the expression of the cardiac (pro)renin receptor ((P)RR) and its downstream signals and whether the blockade of the angiotensin II AT1 receptor by azilsartan decreases the expression of the cardiac (P)RR and its signaling in spontaneously hypertensive rats (SHRs) with a high-salt intake. Rats received normal-salt (0.9%) chow, high-salt (8.9%) chow, normal-salt chow with 1 mg/day of azilsartan, and high-salt chow with 1 mg/day of azilsartan from 6 to 12 weeks of age. Rats with normal-salt chow were administered 100 ng/kg/min of angiotensin II by osmotic minipump from 6 to 12 weeks of age. A high-salt diet and angiotensin II significantly increased the systolic blood pressure; overexpressed cardiac (P)RR, phosphorylated (p)-ERK1/2, p-p38MAPK, p-HSP27, and TGF-ß1; enhanced cardiac interstitial and perivascular fibrosis, cardiomyocyte size, interventricular septum (IVS) thickness, and left ventricular (LV) end-diastolic dimension; and decreased LV fractional shortening. Azilsartan decreased systolic blood pressure, cardiac expressions of (P)RR, p-ERK1/2, p-p38MAPK, p-HSP27, and TGF-ß1, cardiac interstitial and perivascular fibrosis, cardiomyocyte size, and LV diastolic dimension, and improved LV fractional shortening. In conclusion, azilsartan attenuates cardiac damage caused by high salt intake through the downregulation of the cardiac (pro)renin receptor and its downstream signals in SHRs.

Abstract 624: Interactions Between Adenylate Cyclase Type 9 (ADCY9) and Cholesteryl Ester Transfer Protein (CETP) in Atherosclerosis

Pharmacogenomic studies have shown that ADCY9 genotype determines the effects of the cholesteryl ester transfer protein (CETP) inhibitor dalcetrapib on cardiovascular events, atherosclerosis imaging and body weight variation. The underlying mechanisms responsible for the interactions between ADCY9 and CETP have not yet been determined. Adcy9 -inactivated ( Adcy9 Gt/Gt ) and wild-type (WT) mice, that were or not transgenic for the CETP gene (CETP Gt and CETP WT ), were submitted to an atherogenic protocol (injection of an AAV8 expressing a PCSK9 gain-of-function variant and 0.75% cholesterol diet for 16 weeks). Atherosclerosis, cell adhesion, vasorelaxation, telemetry and adipose tissue MRI were evaluated. Adcy9 Gt/Gt mice had a 65% reduction in aortic atherosclerosis compared to WT ( P &lt;0.01). CD68-positive macrophage accumulation and proliferation in plaques were reduced in Adcy9 Gt/Gt mice compared to WT animals ( P &lt;0.05 for both). Adcy9 inactivation did not change counts of blood monocytes and their subsets. Splenocytes showed reduced adhesion to native aortic endothelium from Adcy9 Gt/Gt mice ( P &lt;0.05 vs WT). Femoral artery endothelial-dependent vasorelaxation was improved in Adcy9 Gt/Gt mice (versus WT, P &lt;0.01). Selective pharmacological blockade showed that the nitric oxide, cyclooxygenase and endothelial-dependent hyperpolarization pathways all contributed to the improvement of vasodilatation in Adcy9 Gt/Gt versus WT ( P &lt;0.01 for all). Adcy9 Gt/Gt mice gained more weight than WT with the atherogenic diet, and this was associated with an increase in whole body adipose tissue volume ( P &lt;0.05 for both). Feed efficiency was increased in Adcy9 Gt/Gt compared to WT mice ( P &lt;0.05), which was accompanied by improved nocturnal heart rate variability ( P =0.0572) and prolonged cardiac RR interval ( P &lt;0.05). Adcy9 inactivation-induced effects on atherosclerosis, endothelium-dependent vasodilation, weight gain and feed efficiency were lost in CETP Gt mice ( P &gt;0.05 vs CETP WT ). Adcy9 inactivation protects against atherosclerosis, but only in the absence of CETP activity. This atheroprotection may be explained by decreased macrophage accumulation and proliferation in the arterial wall, improved endothelial function and autonomic tone.

Excessively low salt diet damages the heart through activation of cardiac (pro) renin receptor, renin-angiotensin-aldosterone, and sympatho-adrenal systems in spontaneously hypertensive rats.

ObjectiveA high salt intake causes hypertension and leads to cardiovascular disease. Therefore, a low salt diet is now recommended to prevent hypertension and cardiovascular disease. However, it is still unknown whether an excessively low salt diet is beneficial or harmful for the heart.MethodsWistar Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) received normal salt chow (0.9% salt diet) and excessively low salt chow (0.01% salt diet referred to as saltless diet) for 8 weeks from 8 to 16 weeks of age. The effects of the excessively low salt diet on the cardiac (pro) renin receptor, renin-angiotensin-aldosterone, and sympatho-adrenal systems were investigated.ResultsThe excessively low salt diet did not affect the systolic blood pressure but significantly increased the heart rate both in WKYs and SHRs. The excessively low salt diet significantly elevated plasma renin activity, plasma angiotensin I, II and aldosterone concentrations, and plasma noradrenaline and adrenaline concentrations both in WKYs and SHRs. Cardiac expressions of renin, prorenin, (P)RR, angiotensinogen, and angiotensin II AT1 receptor and phosphorylated (p)-ERK1/2, p-HSP27, p-38MAPK, and TGF-ß1 were significantly enhanced by the excessively low salt diet in both WKYs and SHRs. The excessively low salt diet accelerated cardiac interstitial and perivascular fibrosis and increased the cardiomyocyte size and interventricular septum thickness in WKYs and SHRs but the extent was greater in SHRs.ConclusionAn excessively low salt diet damages the heart through activation of plasma renin-angiotensin-aldosterone and sympatho-adrenal systems and activation of cardiac (P)RR and angiotensin II AT1 receptor and their downstream signals both in WKYs and SHRs.

The sensitivity of 38 heart rate variability measures to the addition of artifact in human and artificial 24-hr cardiac recordings.

Artifact is common in cardiac RR interval data derived from 24-hr recordings and has a significant impact on heart rate variability (HRV) measures. However, the relative impact of progressively added artifact on a large group of commonly used HRV measures has not been assessed. This study compared the relative sensitivity of 38 commonly used HRV measures to artifact to determine which measures show the most change with increasing increments of artifact. A secondary aim was to ascertain whether short-term and long-term HRV measures, as groups, share similarities in their sensitivity to artifact. Up to 10% of artifact was added to 20 artificial RR (ARR) files and 20 human cardiac recordings, which had been assessed for artifact by a cardiac technician. The added artifact simulated deletion of RR intervals and insertion of individual short RR intervals. Thirty-eight HRV measures were calculated for each file. Regression analysis was used to rank the HRV measures according to their sensitivity to artifact as determined by the magnitude of slope. RMSSD, SDANN, SDNN, RR triangular index and TINN, normalized power and relative power linear measures, and most nonlinear methods examined are most robust to artifact. Short-term time domain HRV measures are more sensitive to added artifact than long-term measures. Absolute power frequency domain measures across all frequency bands are more sensitive than normalized and relative frequency domain measures. Most nonlinear HRV measures assessed were relatively robust to added artifact, with Poincare plot SD1 being most sensitive.

Mineralocorticoid receptor antagonists for heart failure: systematic review and meta-analysis.

BackgroundMineralocorticoid receptor antagonists (MRAs) have been associated with improved patient outcomes in patients with heart failure with reduced ejection fraction (HFrEF) but not preserved ejection fraction (HFpEF). We conducted a systematic review and meta-analysis of selective and nonselective MRAs in HFrEF and HFpEF.MethodsWe searched Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE. We included randomized controlled trials (RCT) of MRAs in adults with HFpEF or HFrEF if they reported data on major adverse cardiac events or drug safety.ResultsWe identified 15 studies representing 16321 patients. MRAs were associated with a reduced risk of cardiovascular death (RR 0.81 [0.75–0.87], I2 0%), all-cause mortality (RR 0.83 [0.77–0.88], I2 0%), and cardiac hospitalizations (RR 0.80 [0.70–0.92], I2 58.4%). However, an a-priori specified subgroup analysis demonstrated that these benefits were limited to HFrEF (cardiovascular death RR 0.79 [0.73–0.86], I2 0%; all-cause mortality RR 0.81 [0.75–0.87], I2 0%; cardiac hospitalizations RR 0.76 [0.64–0.90], I2 68%), but not HFpEF (all-cause mortality RR 0.92 [0.79–1.08], I2 0%; cardiac hospitalizations RR 0.91 [0.67–1.24], I2 17%). MRAs increased the risk of hyperkalemia (RR 2.03 [1.78–2.31], I2 0%). Nonselective MRAs, but not selective MRAs increased the risk of gynecomastia (RR 7.37 [4.42–12.30], I2 0% vs. RR 0.74 [0.43–1.27], I2 0%). Evidence was of moderate quality for cardiovascular death, all-cause mortality and cardiovascular hospitalizations; and high-quality for hyperkalemia and gynecomastia.ConclusionsMRAs reduce the risk of adverse cardiac events in HFrEF but not HFpEF. MRA use in HFpEF increases the risk of harm from hyperkalemia and gynecomastia. Selective MRAs are equally effective as nonselective MRAs, without a risk of gynecomastia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-016-0425-x) contains supplementary material, which is available to authorized users.

OS 15-01 ASSOCIATION OF CARDIAC (P) RR AND PLC-b3 EXPRESSION IN RATS WITH AORTIC CONSTRICTION

Objective: Recently, some findings support the (pro) renin-(Pro) renin receptor (P) RR interaction at exceptionally high (pro) renin levels in vitro. The aim of this study was to investigate the roles of cardiac (P) RR and its downward signals on mean arterial pressure (MAP) in rats with abdominal aortic constriction, following treatment of handle region peptide (HRP) and phospholipase C-β3 (PLC-b3) inhibitor, U73122. Design and Method: Seventy-five SD rats were divided into 5 groups (n=15 each group) as following: sham operated (SO), rats with the aortic ligation (AL), AL rats were given HRP (4 μg kg−1 d−1, SC), AL rats given U73122 (40 μg kg−1 d−1, SC) and AL rats given HRP+U73122. MAP was recorded using a tail-cuff method. After 4 weeks of treatment, levels of (P) RR, PLC-b3, PKC-a and ERK1/2 in the heart were examined by RT-PCR and western blot. Results: The levels of (P) RR and PLC-b3 significantly increased in the left ventricle in hypertensive rats (P < 0.01), respectively. MAP rose markedly (P < 0.01). HRP decreased the level of (P) RR and U73122 suppressed PLC-b3 expression. Treatment of both HRP and U73122 significantly decreased levels of PKC-a, ERK1/2 and Raf-1 in the heart (P < 0.001). Meanwhile, MAP was decreased after treatment. Conclusions: This study demonstrates that (P) RR inhibitor, HRP and PLC-b3 inhibitor, U73122 decreased levels of (P) RR, PLC-b3, PKC-a, ERK1/2 and Raf-1 in the heart. Meanwhile, administration of both reagents lowered MAP. These findings indicate that cardiac (P) RR may activate PLC-b3, PKC, ERK1/2 and Raf-1 signals and lead to hypertension. Acknowledgement: This study was supported by the Natural Science Foundation of China (No. 81270336).

PSY52 - ASSESSING BURDEN OF ILLNESS AND HOSPITAL UTILIZATION IN PATIENTS DIAGNOSED WITH HYPERKALEMIA

To examine burden of illness and hospital utilization in patients diagnosed with hyperkalemia. A retrospective cross-sectional study was conducted on MedAssets health system data for inpatient and outpatient visits diagnosed with hyperkalemia for the October 2013 to September 2015 timeframe. Age and gender, clinical comorbidities and measures of utilization including number of visits, length of stay (LOS), and readmissions were described. Multivariable regression was used to identify significant drivers of hospital-based utilization. The hyperkalemia population consisted of 374,720 patients across 406 hospitals with a mean age of 64.7. Of 531,341 visits, 60.6% occurred in the inpatient setting. The most common comorbidities included renal disease (RD 57.8%), diabetes (49.2%), chronic kidney disease (CKD 47.0%), anemia (42.2%), hypertensive CKD (40.5%), and congestive heart failure (CHF 36.6%). When patients were admitted the average LOS was 8.6 days with an average cost of $17,060 and 9.3% 30-day readmission rate. Surgical procedures such as colon diversion (RR=2.3, p<.0001), kidney transplant (RR=1.3, p<.0001), and hemodialysis (RR=1.3, p<.0001) as well as infections (septicemia RR=1.4, p<.0001; pneumonia RR=1.4, p<.0001; Urinary tract infection RR=1.2, p<.0001) and comorbidities (anemia RR=1.2, p<.0001; cardiac dysrhythmia RR=1.1, p<.0001) were associated with longer LOS. Readmissions occurred within 30 days for 9.3% of inpatient admissions with infection (12.4%), CHF (7.5%), and rehabilitation services (6.9%) as the most common primary diagnoses for readmission. 3.2% were readmitted for hyperkalemia. The most common predictors of readmission included severe liver disease (OR=1.4, p<.0001), kidney transplant (OR=1.3, p=.0005), paraplegia/hemiplegia (OR=1.3, p<.0001), anemia (OR=1.2, p<.0001), renal failure (OR=1.2, p<.0001), and CHF (OR=1.2, p<.0001). Hyperkalemia patients are treated primarily in the inpatient setting and are resource intensive with long lengths of stay, high cost and a high rate of readmission within 30 days.

Causal analysis of short-term cardiovascular variability: state-dependent contribution of feedback and feedforward mechanisms.

Baroreflex function is usually assessed from spontaneous oscillations of blood pressure (BP) and cardiac RR interval assuming a unidirectional influence from BP to RR. However, the interaction of BP and RR is bidirectional-RR also influences BP. Novel methods based on the concept of Granger causality were recently developed for separate analysis of feedback (baroreflex) and feedforward (mechanical) interactions between RR and BP. We aimed at assessing the proportion of the two causal directions of the interactions between RR and systolic BP (SBP) oscillations during various conditions, and at comparing causality measures from SBP to RR with baroreflex gain indexes. Arterial BP and ECG signals were noninvasively recorded in 16 young healthy volunteers during supine rest, mental arithmetics, and head-up tilt test, as well as during the combined administration of these stressors. The causal interactions between beat-to-beat RR and SBP signals were analyzed in time, frequency, and information domains. The baroreflex gain was assessed in the frequency domain using non-causal and causal measures of the transfer function from SBP to RR. We found a consistent increase in the baroreflex coupling strength from SBP to RR during head-up tilt, an insensitivity of the coupling strength along the non-baroreflex direction to both stressors, and no significant effect of mental arithmetics on the feedback coupling strength. It indicates that the proportion of causal interactions between SBP and RR significantly varies during different conditions. The increase in the coupling from SBP to RR with tilt was not accompanied by concomitant variations of the transfer function gain, suggesting that causality and gain analyses are complementary and assess different aspects of the baroreflex regulation of heart rate.

A preprocessing tool for removing artifact from cardiac RR interval recordings using three-dimensional spatial distribution mapping.

Artifact is common in cardiac RR interval data that is recorded for heart rate variability (HRV) analysis. A novel algorithm for artifact detection and interpolation in RR interval data is described. It is based on spatial distribution mapping of RR interval magnitude and relationships to adjacent values in three dimensions. The characteristics of normal physiological RR intervals and artifact intervals were established using 24-h recordings from 20 technician-assessed human cardiac recordings. The algorithm was incorporated into a preprocessing tool and validated using 30 artificial RR (ARR) interval data files, to which known quantities of artifact (0.5%, 1%, 2%, 3%, 5%, 7%, 10%) were added. The impact of preprocessing ARR files with 1% added artifact was also assessed using 10 time domain and frequency domain HRV metrics. The preprocessing tool was also used to preprocess 69 24-h human cardiac recordings. The tool was able to remove artifact from technician-assessed human cardiac recordings (sensitivity 0.84, SD = 0.09, specificity of 1.00, SD = 0.01) and artificial data files. The removal of artifact had a low impact on time domain and frequency domain HRV metrics (ranging from 0% to 2.5% change in values). This novel preprocessing tool can be used with human 24-h cardiac recordings to remove artifact while minimally affecting physiological data and therefore having a low impact on HRV measures of that data.