Assessment of right ventricular systolic function: Comparison between cardiac magnetic resonance derived ejection fraction and pulsed-wave tissue Doppler imaging of the tricuspid annulus

Systolic right ventricular (RV) function is an important predictor in the course of various congenital and acquired heart diseases. Its practical determination by echocardiography remains challenging. We compared routine assessment of lateral tricuspid annular systolic motion velocity (TV(lat), cm/s) using pulsed-wave tissue Doppler imaging from the apical 4-chamber view with cardiac magnetic resonance (CMR) as reference method.

Clinical outcome of high-risk patients with severe aortic stenosis and reduced left ventricular ejection fraction undergoing medical treatment or TAVI

Introduction Reduced left ventricular function in patients with severe symptomatic valvular aortic stenosis is associated with impaired clinical outcome in patients undergoing surgical aortic valve replacement (SAVR). Transcatheter Aortic Valve Implantation (TAVI) has been shown non-inferior to SAVR in high-risk patients with respect to mortality and may result in faster left ventricular recovery. Methods We investigated clinical outcomes of high-risk patients with severe aortic stenosis undergoing medical treatment (n = 71) or TAVI (n = 256) stratified by left ventricular ejection fraction (LVEF) in a prospective single center registry. Results Twenty-five patients (35%) among the medical cohort were found to have an LVEF≤30% (mean 26.7±4.1%) and 37 patients (14%) among the TAVI patients (mean 25.2±4.4%). Estimated peri-interventional risk as assessed by logistic EuroSCORE was significantly higher in patients with severely impaired LVEF as compared to patients with LVEF>30% (medical/TAVI 38.5±13.8%/40.6±16.4% versus medical/TAVI 22.5±10.8%/22.1±12.8%, p <0.001). In patients undergoing TAVI, there was no significant difference in the combined endpoint of death, myocardial infarction, major stroke, life-threatening bleeding, major access-site complications, valvular re-intervention, or renal failure at 30 days between the two groups (21.0% versus 27.0%, p = 0.40). After TAVI, patients with LVEF≤30% experienced a rapid improvement in LVEF (from 25±4% to 34±10% at discharge, p = 0.002) associated with improved NYHA functional class at 30 days (decrease ≥1 NYHA class in 95%). During long-term follow-up no difference in survival was observed in patients undergoing TAVI irrespective of baseline LVEF (p = 0.29), whereas there was a significantly higher mortality in medically treated patients with severely reduced LVEF (log rank p = 0.001). Conclusion TAVI in patients with severely reduced left ventricular function may be performed safely and is associated with rapid recovery of systolic left ventricular function and heart failure symptoms.

Value of age, creatinine, and ejection fraction (ACEF score) in assessing risk in patients undergoing percutaneous coronary interventions in the 'All-Comers' LEADERS trial

Background— The age, creatinine, and ejection fraction (ACEF) score (age/left ventricular ejection fraction+1 if creatinine >2.0 mg/dL) has been established as an effective predictor of clinical outcomes in patients undergoing elective coronary artery bypass surgery; however, its utility in “all-comer” patients undergoing percutaneous coronary intervention is yet unexplored. Methods and Results— The ACEF score was calculated for 1208 of the 1707 patients enrolled in the LEADERS trial. Post hoc analysis was performed by stratifying clinical outcomes at the 1-year follow-up according to ACEF score tertiles: ACEFlow ≤1.0225, 1.0225< ACEFmid ≤1.277, and ACEFhigh >1.277. At 1-year follow-up, there was a significantly lower number of patients with major adverse cardiac event–free survival in the highest tertile of the ACEF score (ACEFlow=92.1%, ACEFmid=89.5%, and ACEFhigh=86.1%; P=0.0218). Cardiac death was less frequent in ACEFlow than in ACEFmid and ACEFhigh (0.7% vs 2.2% vs 4.5%; hazard ratio=2.22, P=0.002) patients. Rates of myocardial infarction were significantly higher in patients with a high ACEF score (6.7% for ACEFhigh vs 5.2% for ACEFmid and 2.5% for ACEFlow; hazard ratio=1.6, P=0.006). Clinically driven target-vessel revascularization also tended to be higher in the ACEFhigh group, but the difference among the 3 groups did not reach statistical significance. The rate of composite definite, possible, and probable stent thrombosis was also higher in the ACEFhigh group (ACEFlow=1.2%, ACEFmid=3.5%, and ACEFhigh=6.2%; hazard ratio=2.04, P<0.001). Conclusions— ACEF score may be a simple way to stratify risk of events in patients treated with percutaneous coronary intervention with respect to mortality and risk of myocardial infarction.

Best combination of pre-stimulation and latency period duration before cluster attachment for efficient oxytocin release and milk ejection in cows with low to high udder-filling levels

Experiments were designed to investigate the suitability of a combination of a short manual teat stimulation with a short latency period before teat cup attachment to induce and maintain oxytocin release and milk ejection without interruption. In Experiment 1, seven dairy cows in mid lactation were manually pre-stimulated for 15, 30 or 45 s, followed by either 30 s or 45 s of latency period. It was shown that all treatments induced a similar release of oxytocin without interruption until the end of milking. In particular, the latency period of up to 45 s did not cause a transient decrease of oxytocin concentration. In Experiment 2, milking characteristics were recorded in seven cows each in early, mid, and late lactation, respectively. Because the course of milk ejection depends mainly on the degree of udder filling, individual milkings were classified based on the actual degree of udder filling which differs between lactational stages but also between morning and evening milkings. All animals underwent twelve different udder preparation treatments, i.e. 15, 30, or 45 s of pre-stimulation followed by latency periods of 0, 30, 45, or 60 s. Milking characteristics were recorded. Total milk yield, main milking time and average milk flow rate did not differ between treatments if the degree of udder filling at the start of milking was >40% of the maximum storage capacity. However, if the udder filling was <40%, main milking time was decreased with the duration of a latency period up to 45 s, independent of duration of pre-stimulation. Average milk flow at an udder filling of <40% was highest after a pre-stimulation of 45 s followed by a latency period of another 45 s. In contrast, average milk flow reached its lowest values at a pre-stimulation of 15 s without additional latency period. However, average milk flow after a 15-s pre-stimulation increased with increasing latency period. In conclusion, a very short pre-stimulation when followed by a latency period up to 45 s before teat cup attachment remains a suitable alternative for continuous stimulation to induce milk ejection.

Suitability of low-dosage oxytocin treatment to induce milk ejection in dairy cows

Chronic use of high oxytocin (OT) dosages can cause a reduced response to endogenous OT. In this study the OT dosages used in the milking practice of 82 dairy cow farms were recorded. The OT dosages per cow used were high, especially when injected i.m. (23+/-2 IU) compared with i.v. (7+/-1 IU). In addition, the minimum OT dosages needed to obtain normal milk removal in cows with disturbed milk ejection were investigated. Seventeen cows routinely treated with OT during milking (group T) and 17 cows without previous OT treatment were used (group C). After cessation of spontaneous milk flow, both T and C groups were injected i.v. with a low dosage of OT (0.2 or 0.5 IU/cow). The time from injection until cessation of the OT-induced milk flow was recorded (response phase). The response phase and the amounts of removed milk by effect of the OT injection increased with increasing OT dosage. Values for 0.2 and 0.5 IU/cow of OT injected i.v. were (response phase and amount of milk removed) 198+/-27 and 302+/-18s and 3.4+/-0.7 kg and 6.5+/-1.3 kg, respectively, for the C group, and 157+/-15 and 221+/-16s and 3.2+/-0.5 and 5.5+/-1.0 kg, respectively, for the T group. Within 20 min of the OT injection, plasma concentrations returned to basal levels. The threshold OT concentration at cessation of milk flow after injection of 0.2 or 0.5 IU/cow of OT was calculated based on the OT plasma half-life. The threshold increased with increasing dosages of OT and was higher in group T (8+/-1 and 14+/-1 pg/mL for 0.2 and 0.5 IU/cow, respectively) than in group C (7+/-1 and 11+/-1 pg/mL for 0.2 and 0.5 IU/cow, respectively). In conclusion, desensitization of the udder toward OT occurs when the udder is exposed to elevated OT plasma concentrations, both short-term during the actual milking and long-term due to chronic high-dosage OT treatment. However, low-dosage OT treatments to induce normal milk removal can minimize the observed side effects.

Effects of right ventricular pacing on left ventricular ejection fraction in a pacemaker clinic

The aim of this study was to evaluate whether a change of left ventricular ejection fraction (LVEF) depending on percentage of right ventricular pacing is found in a real-life setting of a pacemaker clinic.

Prediction of arrhythmic events after myocardial infarction based on signal-averaged electrocardiogram and ejection fraction

Trials on implantable cardioverter-defibrillators (ICD) for patients after acute myocardial infarction (AMI) have highlighted the need for risk assessment of arrhythmic events (AE). The aim of this study was to evaluate risk predictors based on a novel approach of interpreting signal-averaged electrocardiogram (SAECG) and ejection fraction (EF).

Milk ejection disorders in Swiss dairy cows: a field study

A questionnaire was sent to 2099 dairy farms to investigate the occurrence of poor milkability. Based on that, the frequency of poor milkability in Swiss dairy cows was 4% and the percentage of cows treated with oxytocin (OT) was 2%. In addition, 270 dairy farms that had reported cases of animals with poor milkability were contacted for an interview to classify the disorders. Farmers suspected disturbed milk ejection in 52%, anatomical dysfunction of the teat and/or the udder in 16% and milk ejection disorder or impaired milkability caused by discernable environmental factors in 32% of the cases. Forty-eight animals from 18 farms with suspected milk ejection disorders were selected for an experimental field study which included milk flow recording and OT administration to induce milk ejection. After cessation of the spontaneous milk flow, a low dose of OT (0.2, 0.5 or 1 i.u.) was injected i.v. to test the responsiveness of the udder to OT at a physiological level. When milk flow ceased again, 10 i.u. OT was injected i.v. (supraphysiological) to ensure complete udder emptying and to determine the residual milk. Milk ejection disorder could be confirmed in 69% of the cases, i.e. if residual milk was >20% of the total milk. Because in 27% of the animals milk ejection disorder was not confirmed on the basis of elevated residual milk, an anatomical disorder of the teat and/or the udder was suspected. Milk ejection disorder could be confirmed in 69% of the cases whereas in 27% of the suspected cases an anatomical disorder of the teat and/or the udder was suspected. An increased cortisol production in cows with milk ejection disorder was not obvious because faecal concentrations of cortisol metabolites with a 5 beta-androstane-3 alpha,11 oxo-structure were not augmented in animals with disturbed milk ejection.

Clinical outcomes of patients with low-flow, low-gradient, severe aortic stenosis and either preserved or reduced ejection fraction undergoing transcatheter aortic valve implantation

AIMS Our aim was to evaluate the invasive haemodynamic indices of high-risk symptomatic patients presenting with 'paradoxical' low-flow, low-gradient, severe aortic stenosis (AS) (PLF-LG) and low-flow, low-gradient severe AS (LEF-LG) and to compare clinical outcomes following transcatheter aortic valve implantation (TAVI) among these challenging AS subgroups. METHODS AND RESULTS Of 534 symptomatic patients undergoing TAVI, 385 had a full pre-procedural right and left heart catheterization. A total of 208 patients had high-gradient severe AS [HGAS; mean gradient (MG) ≥40 mmHg], 85 had PLF-LG [MG ≤ 40 mmHg, indexed aortic valve area [iAVA] ≤0.6 cm(2) m(-2), stroke volume index ≤35 mL/m(2), ejection fraction (EF) ≥50%], and 61 had LEF-LG (MG ≤ 40 mmHg, iAVA ≤0.6 cm(2) m(-2), EF ≤40%). Compared with HGAS, PLF-LG and LEF-LG had higher systemic vascular resistances (HGAS: 1912 ± 654 vs. PLF-LG 2006 ± 586 vs. LEF-LG 2216 ± 765 dyne s m(-5), P = 0.007) but lower valvulo-arterial impedances (HGAS: 7.8 ± 2.7 vs. PLF-LG 6.9 ± 1.9 vs. LEF-LG 7.7 ± 2.5 mmHg mL(-1) m(-2), P = 0.027). At 30 days, no differences in cardiac death (6.5 vs. 4.9 vs. 6.6%, P = 0.90) or death (8.4 vs. 6.1 vs. 6.6%, P = 0.88) were observed among HGAS, PLF-LG, and LEF-LG groups, respectively. At 1 year, New York Heart Association functional improvement occurred in most surviving patients (HGAS: 69.2% vs. PLF-LG 71.7% vs. LEF-LG 89.3%, P = 0.09) and no significant differences in overall mortality were observed (17.6 vs. 20.5 vs. 24.5%, P = 0.67). Compared with HGAS, LEF-LG had a higher 1 year cardiac mortality (adjusted hazard ratio 2.45, 95% confidence interval 1.04-5.75, P = 0.04). CONCLUSION TAVI in PLF-LG or LEF-LG patients is associated with overall mortality rates comparable with HGAS patients and all groups profit symptomatically to a similar extent.

Effects of inspiratory muscle training in patients with heart failure with preserved ejection fraction

BACKGROUND Heart failure with preserved ejection fraction (HFpEF) is remarkably common in elderly people with highly prevalent comorbid conditions. Despite its increasing in prevalence, there is no evidence-based effective therapy for HFpEF. We sought to evaluate whether inspiratory muscle training (IMT) improves exercise capacity, as well as left ventricular diastolic function, biomarker profile and quality of life (QoL) in patients with advanced HFpEF and nonreduced maximal inspiratory pressure (MIP). DESIGN AND METHODS A total of 26 patients with HFpEF (median (interquartile range) age, peak exercise oxygen uptake (peak VO2) and left ventricular ejection fraction of 73 years (66-76), 10 ml/min/kg (7.6-10.5) and 72% (65-77), respectively) were randomized to receive a 12-week programme of IMT plus standard care vs. standard care alone. The primary endpoint of the study was evaluated by positive changes in cardiopulmonary exercise parameters and distance walked in 6 minutes (6MWT). Secondary endpoints were changes in QoL, echocardiogram parameters of diastolic function, and prognostic biomarkers. RESULTS The IMT group improved significantly their MIP (p < 0.001), peak VO2 (p < 0.001), exercise oxygen uptake at anaerobic threshold (p = 0.001), ventilatory efficiency (p = 0.007), metabolic equivalents (p < 0,001), 6MWT (p < 0.001), and QoL (p = 0.037) as compared to the control group. No changes on diastolic function parameters or biomarkers levels were observed between both groups. CONCLUSIONS In HFpEF patients with low aerobic capacity and non-reduced MIP, IMT was associated with marked improvement in exercise capacity and QoL.

C-reactive protein predicts mortality in patients referred for coronary angiography and symptoms of heart failure with preserved ejection fraction

AIMS Heart failure with preserved ejection fraction (HFpEF) has a different pathophysiological background compared to heart failure with reduced ejection fraction (HFrEF). Tailored risk prediction in this separate heart failure group with a high mortality rate is of major importance. Inflammation may play an important role in the pathogenesis of HFpEF because of its significant contribution to myocardial fibrosis. We therefore aimed to assess the predictive value of C-reactive protein (CRP) in patients with HFpEF. METHODS AND RESULTS Plasma levels of CRP were determined in 459 patients with HFpEF in the LUdwigshafen Risk and Cardiovascular Health (LURIC) study using a high-sensitivity assay. During a median follow-up of 9.7 years 40% of these patients died. CRP predicted all-cause mortality with an adjusted hazard ratio (HR) of 1.20 [95% confidence interval (CI) 1.02-1.40, P = 0.018] and cardiovascular mortality with a HR of 1.32 (95% CI 1.08-1.62, P = 0.005) per increase of one standard deviation. CRP was a significantly stronger mortality predictor in HFpEF patients than in a control group of 522 HFrEF patients (for interaction, P = 0.015). Furthermore, CRP added prognostic value to N-terminal pro B-type natriuretic peptide (Nt-proBNP): the lowest 5-year mortality rate of 6.8% was observed for patients in the lowest tertile of Nt-proBNP as well as CRP. The mortality risk peaked in the group combining the highest values of Nt-proBNP and CRP with a 5-year rate of 36.5%. CONCLUSION It was found that CRP was an independent and strong predictor of mortality in HFpEF. This observation may reflect immunological processes with an adverse impact on the course of HFpEF.

Von Willebrand Factor Improves Risk Prediction in Addition to N-Terminal Pro-B-type Natriuretic Peptide in Patients Referred to Coronary Angiography and Signs and Symptoms of Heart Failure and Preserved Ejection Fraction.

BACKGROUND Heart failure with preserved ejection fraction (HFpEF) represents a growing health burden associated with substantial mortality and morbidity. Consequently, risk prediction is of highest importance. Endothelial dysfunction has been recently shown to play an important role in the complex pathophysiology of HFpEF. We therefore aimed to assess von Willebrand factor (vWF), a marker of endothelial damage, as potential biomarker for risk assessment in patients with HFpEF. METHODS AND RESULTS Concentrations of vWF were assessed in 457 patients with HFpEF enrolled as part of the LUdwigshafen Risk and Cardiovascular Health (LURIC) study. All-cause mortality was observed in 40% of patients during a median follow-up time of 9.7 years. vWF significantly predicted mortality with a hazard ratio (HR) per increase of 1 SD of 1.45 (95% confidence interval, 1.26-1.68; P<0.001) and remained a significant predictor after adjustment for age, sex, body mass index, N-terminal pro-B-type natriuretic peptide (NT-proBNP), renal function, and frequent HFpEF-related comorbidities (adjusted HR per 1 SD, 1.22; 95% confidence interval, 1.05-1.42; P=0.001). Most notably, vWF showed additional prognostic value beyond that achievable with NT-proBNP indicated by improvements in C-Statistic (vWF×NT-proBNP: 0.65 versus NT-proBNP: 0.63; P for comparison, 0.004) and category-free net reclassification index (37.6%; P<0.001). CONCLUSIONS vWF is an independent predictor of long-term outcome in patients with HFpEF, which is in line with endothelial dysfunction as potential mediator in the pathophysiology of HFpEF. In particular, combined assessment of vWF and NT-proBNP improved risk prediction in this vulnerable group of patients.

Impact of mitral regurgitation on clinical outcomes of patients with low-ejection fraction, low-gradient severe aortic stenosis undergoing transcatheter aortic valve implantation.

BACKGROUND Up to 1 in 6 patients undergoing transcatheter aortic valve implantation (TAVI) present with low-ejection fraction, low-gradient (LEF-LG) severe aortic stenosis and concomitant relevant mitral regurgitation (MR) is present in 30% to 55% of these patients. The effect of MR on clinical outcomes of LEF-LG patients undergoing TAVI is unknown. METHODS AND RESULTS Of 606 consecutive patients undergoing TAVI, 113 (18.7%) patients with LEF-LG severe aortic stenosis (mean gradient ≤40 mm Hg, aortic valve area <1.0 cm(2), left ventricular ejection fraction <50%) were analyzed. LEF-LG patients were dichotomized into ≤mild MR (n=52) and ≥moderate MR (n=61). Primary end point was all-cause mortality at 1 year. No differences in mortality were observed at 30 days (P=0.76). At 1 year, LEF-LG patients with ≥moderate MR had an adjusted 3-fold higher rate of all-cause mortality (11.5% versus 38.1%; adjusted hazard ratio, 3.27 [95% confidence interval, 1.31-8.15]; P=0.011), as compared with LEF-LG patients with ≤mild MR. Mortality was mainly driven by cardiac death (adjusted hazard ratio, 4.62; P=0.005). As compared with LEF-LG patients with ≥moderate MR assigned to medical therapy, LEF-LG patients with ≥moderate MR undergoing TAVI had significantly lower all-cause mortality (hazard ratio, 0.38; 95% confidence interval, 0.019-0.75) at 1 year. CONCLUSIONS Moderate or severe MR is a strong independent predictor of late mortality in LEF-LG patients undergoing TAVI. However, LEF-LG patients assigned to medical therapy have a dismal prognosis independent of MR severity suggesting that TAVI should not be withheld from symptomatic patients with LEF-LG severe aortic stenosis even in the presence of moderate or severe MR.

Fibroblast Growth Factor 23 Is an Independent and Specific Predictor of Mortality in Patients With Heart Failure and Reduced Ejection Fraction

BACKGROUND Strategies to improve risk prediction are of major importance in patients with heart failure (HF). Fibroblast growth factor 23 (FGF-23) is an endocrine regulator of phosphate and vitamin D homeostasis associated with an increased cardiovascular risk. We aimed to assess the prognostic effect of FGF-23 on mortality in HF patients with a particular focus on differences between patients with HF with preserved ejection fraction and patients with HF with reduced ejection fraction (HFrEF). METHODS AND RESULTS FGF-23 levels were measured in 980 patients with HF enrolled in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study including 511 patients with HFrEF and 469 patients with HF with preserved ejection fraction and a median follow-up time of 8.6 years. FGF-23 was additionally measured in a second cohort comprising 320 patients with advanced HFrEF. FGF-23 was independently associated with mortality with an adjusted hazard ratio per 1-SD increase of 1.30 (95% confidence interval, 1.14-1.48; P<0.001) in patients with HFrEF, whereas no such association was found in patients with HF with preserved ejection fraction (for interaction, P=0.043). External validation confirmed the significant association with mortality with an adjusted hazard ratio per 1 SD of 1.23 (95% confidence interval, 1.02-1.60; P=0.027). FGF-23 demonstrated an increased discriminatory power for mortality in addition to N-terminal pro-B-type natriuretic peptide (C-statistic: 0.59 versus 0.63) and an improvement in net reclassification index (39.6%; P<0.001). CONCLUSIONS FGF-23 is independently associated with an increased risk of mortality in patients with HFrEF but not in those with HF with preserved ejection fraction, suggesting a different pathophysiologic role for both entities.