Assessment of poststress left ventricular ejection fraction by gated SPECT: comparison with equilibrium radionuclide angiocardiography

PURPOSE: We compared left ventricular (LV) ejection fraction obtained by gated SPECT with that obtained by equilibrium radionuclide angiocardiography in a large cohort of patients. METHODS: Within 1 week, 514 subjects with suspected or known coronary artery disease underwent same-day stress-rest (99m)Tc-sestamibi gated SPECT and radionuclide angiocardiography. For both studies, data were acquired 30 min after completion of exercise and after 3 h rest. RESULTS: In the overall study population, a good correlation between ejection fraction measured by gated SPECT and by radionuclide angiocardiography was observed at rest (r=0.82, p<0.0001) and after stress (r=0.83, p<0.0001). In Bland-Altman analysis, the mean differences in ejection fraction (radionuclide angiocardiography minus gated SPECT) were -0.6% at rest and 1.7% after stress. In subjects with normal perfusion (n=362), a good correlation between ejection fraction measured by gated SPECT and by radionuclide angiocardiography was observed at rest (r=0.72, p<0.0001) and after stress (r=0.70, p<0.0001) and the mean differences in ejection fraction were -0.9% at rest and 1.4% after stress. Also in patients with abnormal perfusion (n=152), a good correlation between the two techniques was observed both at rest (r=0.89, p<0.0001) and after stress (r=0.90, p<0.0001) and the mean differences in ejection fraction were 0.1% at rest and 2.5% after stress. CONCLUSION: In a large study population, a good agreement was observed in the evaluation of LV ejection fraction between gated SPECT and radionuclide angiocardiography. However, in patients with perfusion abnormalities, a slight underestimation in poststress LV ejection fraction was observed using gated SPECT as compared to equilibrium radionuclide angiocardiography

Two step ejection of massive stars and the issue of their formation in isolation

In this paper we investigate the combined effect of massive binary ejection from star clusters and a second acceleration of a massive star during a subsequent supernova explosion. We call this the "two-step-ejection" scenario. The main results are: i) Massive field stars produced via the two-step-ejection process can not in the vast majority of cases be traced back to their parent star clusters. These stars can be mistakenly considered as massive stars formed in isolation. ii) The expected O star fraction produced via the two-step-ejection process is of the order of 1-4 per cent, in quantitative agreement with the observed fraction of candidates for isolated-O-star formation. iii) Stars ejected via the two-step-ejection process can get a higher final velocity (up to 1.5-2 times higher) than the pre-supernova velocity of the massive-star binary.Comment: Accepted by MNRA

The Relationship between Nocturnal Hypoxemia and Left Ventricular Ejection Fraction in Congestive Heart Failure Patients

Background: sleep – disordered breathing ( SDB) is Frequently observed in Patients with Congestive heart Failure. This Study examines the Prevalence of sleep disorder in stable heart failure Patients regardless of ejection Fraction. Method: By Means of echocardiography 108 Patients with Left ventricular ejection Fraction ≤ 45% Were divided into Mild CHF, Moderate CHF and sever CHF. Hypoxemia was Recorded For 1 nights in the hospital was measure by Pulsoximetry. Resalts: In the 108 Patients with CHF, 44 ( 40/7%) had sever CHF, 17 ( 15/7%) moderote CHF 47( 43/6%) Mild CHF. 95 (% 88) of Patients with CHF has abnormal Petterns of nocturnal desaturation Suggestive of cheynestkes respiration. Ejecion Fraction Correlated negatively with dip freqnency. There was no correlation between Desaturation with BMI and snoring. Conclusion: This Study Confirm Strong associations between Sleep apnea and heart disease in Patients with CHF. Low Ejection Fraction Was related to dip frequency. These data suggest that People with congestive heart Failure Should be regarded as a risk group for sleep Apnea

Biomarker profiles of acute heart failure patients with a mid-range ejection fraction

OBJECTIVES: In this study, the authors used biomarker profiles to characterize differences between patients with acute heart failure with a midrange ejection fraction (HFmrEF) and compare them with patients with a reduced (heart failure with a reduced ejection fraction [HFrEF]) and preserved (heart failure with a preserved ejection fraction [HFpEF]) ejection fraction. BACKGROUND: Limited data are available on biomarker profiles in acute HFmrEF. METHODS: A panel of 37 biomarkers from different pathophysiological domains (e.g., myocardial stretch, inflammation, angiogenesis, oxidative stress, hematopoiesis) were measured at admission and after 24 h in 843 acute heart failure patients from the PROTECT trial. HFpEF was defined as left ventricular ejection fraction (LVEF) of ≥50% (n = 108), HFrEF as LVEF of &lt;40% (n = 607), and HFmrEF as LVEF of 40% to 49% (n = 128). RESULTS: Hemoglobin and brain natriuretic peptide levels (300 pg/ml [HFpEF]; 397 pg/ml [HFmrEF]; 521 pg/ml [HFrEF]; ptrend &lt;0.001) showed an upward trend with decreasing LVEF. Network analysis showed that in HFrEF interactions between biomarkers were mostly related to cardiac stretch, whereas in HFpEF, biomarker interactions were mostly related to inflammation. In HFmrEF, biomarker interactions were both related to inflammation and cardiac stretch. In HFpEF and HFmrEF (but not in HFrEF), remodeling markers at admission and changes in levels of inflammatory markers across the first 24 h were predictive for all-cause mortality and rehospitalization at 60 days (pinteraction &lt;0.05). CONCLUSIONS: Biomarker profiles in patients with acute HFrEF were mainly related to cardiac stretch and in HFpEF related to inflammation. Patients with HFmrEF showed an intermediate biomarker profile with biomarker interactions between both cardiac stretch and inflammation markers. (PROTECT-1: A Study of the Selective A1 Adenosine Receptor Antagonist KW-3902 for Patients Hospitalized With Acute HF and Volume Overload to Assess Treatment Effect on Congestion and Renal Function; NCT00328692)

Autonomic regulation therapy to enhance myocardial function in heart failure patients: the ANTHEM-HFpEF study.

BackgroundApproximately half of the patients presenting with new-onset heart failure (HF) have HF with preserved left ventricular ejection fraction (HFpEF) and HF with mid-range left ventricular ejection fraction (HFmrEF). These patients have neurohormonal activation like that of HF with reduced ejection fraction; however, beta-blockers and angiotensin-converting enzyme inhibitors have not been shown to improve their outcomes, and current treatment for these patients is symptom based and empiric. Sympathoinhibition using parasympathetic stimulation has been shown to improve central and peripheral aspects of the cardiac nervous system, reflex control, induce myocyte cardioprotection, and can lead to regression of left ventricular hypertrophy. Beneficial effects of autonomic regulation therapy (ART) using vagus nerve stimulation (VNS) have also been observed in several animal models of HFpEF, suggesting a potential role for ART in patients with this disease.MethodsThe Autonomic Neural Regulation Therapy to Enhance Myocardial Function in Patients with Heart Failure and Preserved Ejection Fraction (ANTHEM-HFpEF) study is designed to evaluate the feasibility, tolerability, and safety of ART using right cervical VNS in patients with chronic, stable HFpEF and HFmrEF. Patients with symptomatic HF and HFpEF or HFmrEF fulfilling the enrolment criteria will receive chronic ART with a subcutaneous VNS system attached to the right cervical vagus nerve. Safety parameters will be continuously monitored, and cardiac function and HF symptoms will be assessed every 3 months during a post-titration follow-up period of at least 12 months.ConclusionsThe ANTHEM-HFpEF study is likely to provide valuable information intended to expand our understanding of the potential role of ART in patients with chronic symptomatic HFpEF and HFmrEF

Relation of Gallbladder Motility to Viscosity and Composition of Gallbladder Bile in Patients with Cholesterol Gallstones

Background/Aims: Increased viscosity and supersaturation of cholesterol in gallbladder bile, as well as an impaired motility of the gallbladder, are considered to be important factors in the pathogenesis of cholesterol gallstones. However, the relation of these parameters has not yet been determined. Material and Methods: Bile viscosity (mPa.s) was measured by rotation viscosimetry and the composition of gallbladder bile was determined using standard methodology. Gallbladder motility was calculated as ejection fraction in percent of total volume 45 min after a test meal using ultrasonography in patients with gallstones prior to elective cholecystectomy. Results: The study included 35 patients with cholesterol gallstones. Viscosity of gallbladder bile ranged between 0.9 and 12.5 mPa.s (median 2.2 mPa.s) and an ejection fraction of the gallbladder of 55.4 +/- 18.3% (mean +/- SD) was determined. No significant correlation (r = 0.19, p < 0.2) between the 2 parameters could be calculated. Analysis of the composition of gallbladder bile revealed a positive correlation of all components to biliary viscosity but not to the motility of the gallbladder, with the exceptions of a negative correlation (r = 0.39, p < 0.02) between mucin concentration and the ejection fraction at 45 min after the test meal. Conclusions: The motility of the gallbladder appears to be unrelated to the viscosity of gallbladder bile or gallbladder bile composition. The negative correlation between the ejection fraction of the gallbladder and mucin concentration of gallbladder bile suggests that chronic inflammation of the gallbladder wall is associated with both an impaired motility of the gallbladder and increased mucin release into gallbladder bile. Copyright (C) 2009 S. Karger AG, Base

One-year outcomes after transcatheter insertion of an interatrial shunt device for the management of heart failure with preserved ejection fraction

Background—Heart failure with preserved ejection fraction has a complex pathophysiology and remains a therapeutic challenge. Elevated left atrial pressure, particularly during exercise, is a key contributor to morbidity and mortality. Preliminary analyses have demonstrated that a novel interatrial septal shunt device that allows shunting to reduce the left atrial pressure provides clinical and hemodynamic benefit at 6 months. Given the chronicity of heart failure with preserved ejection fraction, evidence of longer-term benefit is required. Methods and Results—Patients (n=64) with left ventricular ejection fraction ≥40%, New York Heart Association class II–IV, elevated pulmonary capillary wedge pressure (≥15 mm Hg at rest or ≥25 mm Hg during supine bicycle exercise) participated in the open-label study of the interatrial septal shunt device. One year after interatrial septal shunt device implantation, there were sustained improvements in New York Heart Association class (P&lt;0.001), quality of life (Minnesota Living with Heart Failure score, P&lt;0.001), and 6-minute walk distance (P&lt;0.01). Echocardiography showed a small, stable reduction in left ventricular end-diastolic volume index (P&lt;0.001), with a concomitant small stable increase in the right ventricular end-diastolic volume index (P&lt;0.001). Invasive hemodynamic studies performed in a subset of patients demonstrated a sustained reduction in the workload corrected exercise pulmonary capillary wedge pressure (P&lt;0.01). Survival at 1 year was 95%, and there was no evidence of device-related complications. Conclusions—These results provide evidence of safety and sustained clinical benefit in heart failure with preserved ejection fraction patients 1 year after interatrial septal shunt device implantation. Randomized, blinded studies are underway to confirm these observations

Novel pathways of heart failure with preserved ejection fraction

INTRODUCTION: Diastolic heart failure (HF) i.e., HF with preserved ejection fraction (HFpEF) accounts for ~50% of all clinical HF presentations; but unlike systolic HF i.e., HF with reduced ejection fraction (HFrEF), there are no evidenced based therapies. Obesity is commonly associated with HFpEF. However, there exist a sub-group of obese patients that exhibit a higher survival rate to HFpEF as compared to average patients. Hypertension is the most important risk factor for HFpEF, with a prevalence of 60-89% reported by large controlled trials, epidemiological studies and HF registries. HFpEF morbidity and mortality rates are staggering: 50-60% 5 year mortality rate, 50% 6 month rehospitalization rate and severe clinical disability. However, there remains an incomplete mechanistic understanding about HFpEF. OBJECTIVES: We wanted to explore new pathways related to HFpEF in order to better understand the mechamisms behind its pathophysiology. To do so, we first wanted to explore the potential crosstalk between the heart and adipose tissue during HFpEF by analyzing the adipose tissue in our HFpEF model. Secondly, we sought to test the hypothesis that chronic ETA/ETB inhibition with macitentan (mac) modulates pathologic cardiac remodeling in hypertension-induced HFpEF. METHODS: Mice (20-25 g) were anesthetized, underwent uninephrectomy and received either a continuous infusion of saline (sham) or d-aldosterone (0.3 ug/hour for 4-weeks via osmotic minipumps). All mice were maintained on standard rodent chow and 1.0% sodium chloride drinking water for 4 weeks and then harvested. Second group of mice underwent the same surgical procedure and infusion. They were maintained on standard chow for 2 weeks and then each group was randomized to chow containing macitentan (30 mg/kg/day, HFpEFmac) or standard rodent chow. After 2 additional weeks, the 4 groups of mice (n=4-8/group) were harvested. Blood pressure (BP) was obtained weekly. Prior to sacrifice, body weight and echocardiography parameters (total wall thickness (TWT) and relative wall thickness (RWT)) were determined. We also obtained diastolic dysfunction parameters including deceleration time (DT), isovolumetric relaxation time (IVRT), and E/A ratio. Furthermore, we measured organ weight after harvesting the mice and obtained histological images for the adipose tissues collected. Glucose tolerance test and acute cold tolerance test were performed on HFpEF mice to determine their metabolic state. RESULTS: HFpEF mice developed hypertension, LV hypertrophy, and diastolic dysfunction. Epididymal and inguinal adipose tissue showed significantly reduced weight and adipocyte size. HFpEF mice displayed regular glucose metabolism but were not able to endure a cold tolerance test as their body temperature dropped too low. After 4 weeks, there was no difference in body weight between sham, HFpEF, shammac and HFpEFmac. As expected HFpEF increased systolic BP (117±14 vs 133±16mmHg; P=NS); macitentan did not lower systolic BP after 2 weeks in either shammac or HFpEFmac. Similarly there was no difference in systolic BP between HFpEF and HFpEFmac. Both kidney and spleen weights were increased in HFpEF but not altered by macitentan therapy. There was no change in lung congestion as measured by wet-dry lung ratio. HFpEF increased TWT (0.998±0.04 vs. 0.79±0.11 mm; P<0.01 vs. sham) and RWT (0.686± 0.10 vs. 0.476±0.05 mm; P<0.001 vs. sham) but were modulated by macitentan (HFpEF vs. HFpEFmac; P<0.05 and P<0.001, respectively). There was no difference in chamber size between HFpEF and HFpEFmac. Similarly, IVRT, DT, left ventricular ejection fraction were no different between HFpEF and and HFpEFmac. Furthermore E/A ratio was increased in HFpEF but was not affected by macitentan CONCLUSIONS: Adipose tissue collected from our HFpEF mice displayed a very different phenotype. This demonstrates that inter-tissue communication is definitely occurring between the adipose tissue and the heart. Further research is required to explore what that communication encompasses and how they can be used to improve HFpEF. Macitentan did not lower systolic BP in sham or mice with HFpEF after the development of hypertension. Diastolic dysfunction, as measured by an increased E/A ratio, was not affected by macitentan. Macitentan significantly modulated TWT and RWT after 2 weeks of therapy. It is thus plausible that macitentan may improve HFpEF by improving adverse cardiac remodeling

Heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) has recently emerged as a major cause of cardiovascular morbidity and mortality. Contrary to initial beliefs, HFpEF is now known to be as common as heart failure with reduced ejection fraction (HFrEF) and carries an unacceptably high mortality rate. With a prevalence that has been steadily rising over the past two decades, it is very likely that HFpEF will represent the dominant heart failure phenotype over the coming few years. The scarcity of trials in this semi-discrete form of heart failure and lack of unified enrolment criteria in the studies conducted to date might have contributed to the current absence of specific therapies. Understanding the epidemiological, pathophysiological and molecular differences (and similarities) between these two forms of heart failure is cornerstone to the development of targeted therapies. Carefully designed studies that adhere to unified diagnostic criteria with the recruitment of appropriate controls and adoption of practical end-points are urgently needed to help identify effective treatment strategies

What can we learn from SOCRATES: more questions than answers?

This editorial refers to ‘Vericiguat in patients with worsening chronic heart failure and preserved ejection fraction: results of the SOluble guanylate Cyclase stimulatoR in heArT failurE patientS with PRESERVED EF (SOCRATES-PRESERVED) Study’, by B. Pieske et al., on page 1119