[Show abstract][Hide abstract] ABSTRACT: Since 2008, the German Cardiac Society (DGK) has been establishing a network of certified chest pain units (CPUs). The goal of CPUs was and is to carry out differential diagnostics of acute or newly occurring chest pain of undetermined origin in a rapid and goal-oriented manner and to take immediate therapeutic measures. The basis for the previous certification process was criteria that have been established and published by the task force on CPUs. These criteria regulate the spatial and technical requirements and determine diagnostic and therapeutic strategies in patients with chest pain. Furthermore, the requirements for the organization of CPUs and the training requirements for the staff of a CPU are defined. The certification process is carried out by the DGK; currently, 225 CPUs are certified and 139 CPUs have been recertified after running for a period of 3 years. The certification criteria have now been revised and updated according to new guidelines.
Clinical Research in Cardiology 07/2015; DOI:10.1007/s00392-015-0888-2 · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Chronic heart failure (CHF) results in limb and respiratory muscle weakness, which contributes to exercise intolerance and increased morbidity and mortality, yet the molecular mechanisms remain poorly understood.Therefore, we aimed to compare parameters of antioxidative capacity, energy metabolism, and catabolic/anabolic balance in diaphragm and quadriceps muscle in an animal model of CHF.Methods
Ligation of the left anterior descending coronary artery (n = 13) or sham operation (n = 11) was performed on Wistar Kyoto rats. After 12 weeks, echocardiography and invasive determination of maximal rates of left ventricular (LV) pressure change were performed. Antioxidative and metabolic enzyme activities and expression of catabolic/anabolic markers were assessed in quadriceps and diaphragm muscle.ResultsLigated rats developed CHF (i.e. severe LV dilatation, reduced LV ejection fraction, and impaired maximal rates of LV pressure change; P < 0.001). There was a divergent response for antioxidant enzymes between the diaphragm and quadriceps in CHF rats, with glutathione peroxidase and manganese superoxide dismutase activity increased in the diaphragm but reduced in the quadriceps relative to shams (P < 0.01). Metabolic enzymes were unaltered in the diaphragm, but cytochrome c oxidase activity (P < 0.01) decreased and lactate dehydrogenase activity (P < 0.05) increased in the quadriceps of CHF animals. Protein expression of the E3 ligase muscle ring finger 1 and proteasome activity were increased (P < 0.05) in both the diaphragm and quadriceps in CHF rats compared with shams.Conclusion
Chronic heart failure induced divergent antioxidative and metabolic but similar catabolic responses between the diaphragm and quadriceps. Despite the quadriceps demonstrating significant impairments in CHF, apparent beneficial adaptations of an increased antioxidative capacity were induced in the diaphragm. Nevertheless, muscle ring finger 1 and proteasome activity (markers of protein degradation) were elevated and oxidative enzyme activity failed to increase in the diaphragm of CHF rats, which suggest that a myopathy is likely present in respiratory muscle in CHF, despite its constant activation.
Journal of Cachexia, Sarcopenia and Muscle 04/2015; DOI:10.1002/jcsm.12034 · 7.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Since 2008 the German Cardiac Society (DGK) has been establishing a network of certified chest pain units (CPUs). The goal of CPUs was and is to carry out differential diagnostics of acute or newly occurring chest pain of undetermined origin in a rapid and goal-oriented manner and to take immediate therapeutic measures. The basis for the previous certification process were criteria that have been established and published by the task force on CPUs. These criteria regulate the spatial and technical requirements and determine diagnostic and therapeutic strategies in patients with chest pain. Furthermore, the requirements for the organization of CPUs and the training requirements for the staff of a CPU are defined. The certification process is carried out by the DGK and currently 206 CPUs are certified and 128 CPUs have been recertified after running for a period of 3 years. The certification criteria have now been revised and updated according to new guidelines.
[Show abstract][Hide abstract] ABSTRACT: Background
Cardiogenic shock (CS) complicating acute myocardial infarction (AMI) is associated with high mortality. Previous studies regarding gender-specific differences in CS are conflicting and there are insufficient data for the presence of gender-associated differences in the contemporary percutaneous coronary intervention era. Aim of this study was therefore to investigate gender-specific differences in a large cohort of AMI patients with CS undergoing contemporary treatment.
In the randomized Intra-aortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial, 600 patients with CS complicating AMI undergoing early revascularization were assigned to therapy with or without intra-aortic balloon pump. We compared sex-specific differences in these patients with regard to baseline and procedural characteristics as well as short- and long-term clinical outcome.
Of 600 patients 187 (31 %) were female. Women were significantly older than men and had a significantly lower systolic and diastolic blood pressure at presentation (p
Clinical Research in Cardiology 10/2014; 104(1). DOI:10.1007/s00392-014-0767-2 · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Limited data exist regarding baseline characteristics and management of heart failure with reduced ejection fraction (EF) in tertiary care facilities.
EVITA-HF comprises web-based case report data on demography, comorbidities, diagnostic and therapy measures, quality of life, adverse events and 1-year follow-up of patients hospitalized for chronic heart failure and an ejection fraction of less than 40%.
Between February 2009 and June 2011, a total of 1,853 consecutive, hospitalized patients (pts) were included in 16 centers in Germany. Mean age was 70 years, 76% were male. Median EF was 30%, and 63% were in NYHA III/IV. Ischemic cardiomyopathy was present in 56%, history of hypertension in 76%, diabetes in 39%, impaired renal function in 33%, thyroid dysfunction in 12%, and malignoma in 7%. Sixty-eight percent of pts had a non-elective admission. Rhythm was sinus/atrial fibrillation or flutter/pacemaker in 64, 28 and 11%, respectively. Median heart rate amounted to 80 bpm, median blood pressure to 122/74 mmHg. LBBB was present in 26% of non-pacemaker pts. Eighteen percent had an ICD or CRT-D. Medication (admission vs. discharge) consisted of ACEI or ARB in 73 vs. 88%, β-blocker in 71 vs. 89%, mineral corticosteroid receptor antagonist (MRA) in 32 vs. 57%, diuretics in 68 vs. 83% (p < 0.001 for each). Forty-two percent of pts received a specific treatment procedure beyond pharmacotherapy, of these 48% revascularization, 39% device therapy, 14% electrical cardioversion, 5% ablation procedures, 9 % valvular procedures, 6% iv inotropes, 1.8% IABP or LVAD implantation. At discharge, 33% of survivors had ICD- or CRT-D implants. One-year mortality amounted to 16.8%, and death or rehospitalization to 56%. NYHA class III/IV was found in 30% (p < 0.001 vs. index admission), general health status was improved in 45% and unchanged in 36% of patients. Eighty-five percent of pts took ACEI or ARB, 86% β-blockers, 47% MRA, and 78% diuretics (p < 0.001 vs. index discharge for all).
Patients with chronic heart failure and low ejection fraction represent an elderly and multimorbid population. While hospitalized, they experience a significant optimization of prognosis-relevant medication, revascularization and device therapy. After 1 year, mortality is moderate; drug adherence is high and NYHA status favourable. The EVITA-HF registry is able to reflect coherently the real-world management, efforts and follow-up in heart failure pts managed in tertiary care facilities.
Clinical Research in Cardiology 07/2014; 103(12). DOI:10.1007/s00392-014-0743-x · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
Residual aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) has been associated with increased mortality. Nevertheless, a considerable proportion of these patients survives and appears to tolerate AR. Identification of patients at higher risk of death may assist in tailoring therapy, but predictors of mortality in this subset of patients is largely unknown.
A total of 1432 patients were included in the German TAVI registry. One-year follow-up data were available for 1318 patients (92%). Of the latter, 201 patients (15.2%) had more-than-mild AR as evaluated by angiography and represent the population of the current analysis. Among these patients, baseline demographic, clinical, echocardiographic and angiographic characteristics were compared among survivors and non-survivors to identify factors associated with mortality at 1 year.
Mean age was 81.2±6.6 years and men represented 55%. The mean logistic EuroSCORE was 22±15%. Overall, 92% of patients received the Medtronic CoreValve and 8% received the Edwards Sapien valve. At 1 year, 61 patients (31%) with more-than-mild post-TAVI AR had died. Compared with patients who survived, patients who died had more commonly coronary artery disease, peripheral arterial disease and chronic renal impairment. Patients who died had a lower baseline LVEF (44±18% vs 52±16%, p=0.002), higher prevalence of more-than-mild (≥2+) mitral regurgitation (44% vs 27%, p=0.001), and a higher systolic pulmonary artery pressure (51±18 mm Hg vs 44±19 mm Hg, p=0.002), but the severity of aortic stenosis was similar, and the prevalence and severity of pre-TAVI AR was comparable (any AR in 88% vs 83%, respectively, p=0.29). Using Cox regression analysis, only baseline mitral regurgitation ≥2+ (HR 1.77, 95% CI 1.05 to 2.99, p=0.03) and systolic pulmonary artery pressure (HR 1.15, 95% CI 1.01 to 1.33, p=0.04) were independently associated with 1-year mortality, while female gender was protective (HR 0.54, 95% CI 0.30 to 0.96, p=0.03).
We identified preprocedural characteristics associated with 1-year mortality in patients with more-than-mild AR after TAVI. More-than-mild baseline mitral regurgitation, higher systolic pulmonary artery pressure and male gender were independently associated with worse outcome.
[Show abstract][Hide abstract] ABSTRACT: Background:
In the REPAIR-AMI trial, intracoronary infusion of bone marrow-derived cells (BMCs) was associated with a significantly greater recovery of contractile function in patients with acute myocardial infarction (AMI) at 4-month follow-up than placebo infusion. The current analysis investigates clinical outcome and predictors of event-free survival at 5 years.
Methods and results:
In the multicentre, placebo-controlled, double-blind REPAIR-AMI trial, 204 patients received intracoronary infusion of BMCs (n = 101) or placebo (n = 103) into the infarct vessel 3-7 days following successful percutaneous coronary intervention. Fifteen patients died in the placebo group compared with seven patients in the BMC group (P = 0.08). Nine placebo-treated patients and five BMC-treated patients required rehospitalization for chronic heart failure (P = 0.23). The combined endpoint cardiac/cardiovascular/unknown death or rehospitalisation for heart failure was more frequent in the placebo compared with the BMC group (18 vs. 10 events; P = 0.10). Univariate predictors of adverse outcomes were age, the CADILLAC risk score, aldosterone antagonist and diuretic treatment, changes in left ventricular ejection fraction, left ventricular end-systolic volume, and N-terminal pro-Brain Natriuretic Peptide (all P < 0.01) at 4 months in the entire cohort and in the placebo group. In contrast, in the BMC group, only the basal (P = 0.02) and the stromal cell-derived factor-1-induced (P = 0.05) migratory capacity of the administered BMC were associated with improved clinical outcome.
In patients of the REPAIR-AMI trial, established clinical parameters are associated with adverse outcome at 5 years exclusively in the placebo group, whereas the migratory capacity of the administered BMC determines event-free survival in the BMC-treated patients. These data disclose a potency-effect relationship between cell therapy and long-term outcome in patients with AMI.
European Heart Journal 05/2014; 35(19):1275-1283. DOI:10.1093/eurheartj/ehu062 · 15.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Mineralocorticoid antagonists improve survival among patients with chronic, severe systolic heart failure and heart failure after myocardial infarction. We evaluated the effects of eplerenone in patients with chronic systolic heart failure and mild symptoms. METHODS: In this randomized, double-blind trial, we randomly assigned 2737 patients with New York Heart Association class II heart failure and an ejection fraction of no more than 35% to receive eplerenone (up to 50 mg daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure. RESULTS: The trial was stopped prematurely, according to prespecified rules, after a median follow-up period of 21 months. The primary outcome occurred in 18.3% of patients in the eplerenone group as compared with 25.9% in the placebo group (hazard ratio, 0.63; 95% confidence interval [CI], 0.54 to 0.74; P<0.001). A total of 12.5% of patients receiving eplerenone and 15.5% of those receiving placebo died (hazard ratio, 0.76; 95% CI, 0.62 to 0.93; P=0.008); 10.8% and 13.5%, respectively, died of cardiovascular causes (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Hospitalizations for heart failure and for any cause were also reduced with eplerenone. A serum potassium level exceeding 5.5 mmol per liter occurred in 11.8% of patients in the eplerenone group and 7.2% of those in the placebo group (P<0.001). CONCLUSIONS: Eplerenone, as compared with placebo, reduced both the risk of death and the risk of hospitalization among patients with systolic heart failure and mild symptoms. (Funded by Pfizer; ClinicalTrials.gov number, NCT00232180.).
[Show abstract][Hide abstract] ABSTRACT: The aim of this analysis is to examine the influence of gender differences on the outcome after transcatheter aortic valve implantation (TAVI) from a multicenter real-world registry in Germany (TAVI registry).
The impact of gender differences on the clinical outcome after TAVI was examined in small studies with conflicting results.
Consecutive patients (n = 1,432) undergoing TAVI in the period between January 2009 and June 2010 in Germany were evaluated. Differences in all-cause mortality were examined with Kaplan-Meier estimates and proportional hazards models.
Women comprised 57.8 % of the cohort. The Edwards Sapien valve (18.5 %) and CoreValve (81.5 %) were used through the transfemoral (87.7 %), subclavian (3.0 %), transapical (8.6 %), or transaortic approach (0.7 %). At baseline, women had higher aortic gradients and were older. Men had more comorbidities: prior myocardial infarction, prior revascularization, prior coronary artery bypass surgery, peripheral arterial vascular disease and chronic obstructive pulmonary disease. Women had more periprocedural vascular complications in comparison to men (25.2 vs. 17.2 %, p < 0.001). There was no significant difference in mortality at 30-day follow-up (7.6 % for women vs. 8.6 % for men, p = 0.55). The adjusted HR for 1-year all-cause mortality favored women, HR 0.75 (95 % CI 0.57-0.98, p = 0.0346) with a mortality rate of 17.3 vs. 23.6 % for men.
Female gender is associated with better 1-year survival after TAVI. These results suggest that TAVI could be the best treatment modality for elderly women with symptomatic severe aortic stenosis.
Clinical Research in Cardiology 03/2014; 103(8). DOI:10.1007/s00392-014-0690-6 · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Die heute vorhandenen Therapieoptionen der koronaren Herzkrankheit (KHK) erfordern ein differenziertes, auf den einzelnen Patienten zugeschnittenes, therapeutisches Vorgehen. Grundlage der KHK-Therapie sind Lifestyle-Modifikationen, die je nach individuellem Risikoprofil des Patienten gezielte Schwerpunkte setzen. Die pharmakologische Therapie der KHK hat das Ziel, präventiv Sekundärereignisse zu verhindern (Thrombozytenaggregationshemmer, Statine) und abhängig vom Ausmaß der Beschwerden antianginös wirksam zu sein (kurzwirksame Nitrate, Betablocker, Kalziumantagonisten, ggf. Ivabradin, Ranolazin). Während bei akuten Koronarsyndromen eine umgehende Koronarrevaskularisation erforderlich ist, ist die Entscheidung zur Revaskularisation bei stabiler KHK von der Symptomatik, einer Ischämie-/Vitalitätsdiagnostik sowie ergänzenden invasiven Verfahren (fraktionelle Flussreserve, intravaskulärer Ultraschall) abhängig. Die Differenzialindikation perkutane Koronarintervention (PCI) versus aortokoronare Bypass-Operation orientiert sich insbesondere an Koronarstatus (SYNTAX-Score), Allgemeinzustand und Willen des Patienten. Die internationalen Leitlinien betonen dabei die Rolle einer interdisziplinären Therapieentscheidung im ,,Heart Team“. Insgesamt stellt die Differenzialtherapie der KHK heute ein herausforderndes Gebiet der Patientenversorgung dar, auf dem zukünftig noch viele weitere Entwicklungen zu erwarten sind.
[Show abstract][Hide abstract] ABSTRACT: The various contemporary therapeutic options for coronary artery disease (CAD) require differentiated, individualized treatment strategies. The foundations of CAD therapy are lifestyle modifications targeted on the individual risk profile of the patients. Pharmacological therapy of CAD should prevent secondary coronary events (e.g. platelet aggregation inhibitors and statins) and reduce angina in symptomatic patients (e.g. short-acting nitrates, beta blockers, calcium channel blockers and if necessary ivabradine and ranolazine). Revascularization therapy has to be performed promptly in patients with acute coronary syndromes; however, in patients with stable CAD the decision to perform revascularization therapy has to consider symptoms, detection of ischemia and if appropriate intracoronary assessment of hemodynamic relevance of an intermediate stenosis (fractional flow reserve). The differential indications of percutaneous coronary intervention compared to coronary artery bypass grafting depend on the severity of coronary artery disease and the morphology (SYNTAX score), comorbidities and the will of the individual patient. The international guidelines emphasize the value of an interdisciplinary treatment decision in a "heart team". In summary, differential therapy of CAD has become challenging in the current clinical practice; future developments will probably further improve individualized strategies to treat patients with CAD.
[Show abstract][Hide abstract] ABSTRACT: IMPORTANCE Myocardial ischemia in patients with stable coronary artery disease (CAD) has been repeatedly associated with impaired survival. However, it is unclear if revascularization with percutaneous coronary intervention (PCI) to relieve ischemia improves outcomes compared with medical therapy (MT). OBJECTIVE The objective of this study was to compare the effect of PCI and MT with MT alone exclusively in patients with stable CAD and objectively documented myocardial ischemia on clinical outcomes. DATA SOURCES MEDLINE, Cochrane, and PubMed databases from 1970 to November 2012. Unpublished data were obtained from investigators. STUDY SELECTION Randomized clinical trials of PCI and MT vs MT alone for stable coronary artery disease in which stents and statins were used in more than 50% of patients. DATA EXTRACTION For studies in which myocardial ischemia diagnosed by stress testing or fractional flow reserve was required for enrollment, descriptive and quantitative data were extracted from the published report. For studies in which myocardial ischemia was not a requirement for enrollment, authors provided data for only those patients with ischemia determined by stress testing prior to randomization. The outcomes analyzed included death from any cause, nonfatal myocardial infarction (MI), unplanned revascularization, and angina. Summary odds ratios (ORs) were obtained using a random-effects model. Heterogeneity was assessed using the Q statistic and I2. RESULTS In 5 trials enrolling 5286 patients, myocardial ischemia was diagnosed in 4064 patients by exercise stress testing, nuclear or echocardiographic stress imaging, or fractional flow reserve. Follow-up ranged from 231 days to 5 years (median, 5 years). The respective event rates for PCI with MT vs MT alone for death were 6.5% and 7.3% (OR, 0.90 [95% CI, 0.71-1.16); for nonfatal MI, 9.2% and 7.6% (OR, 1.24 [95% CI, 0.99-1.56]); for unplanned revascularization, 18.3% and 28.4% (OR, 0.64 [95% CI, 0.35-1.17); and for angina, 20.3% and 23.3% (OR, 0.91 [95% CI, 0.57-1.44]). CONCLUSIONS AND RELEVANCE In patients with stable CAD and objectively documented myocardial ischemia, PCI with MT was not associated with a reduction in death, nonfatal MI, unplanned revascularization, or angina compared with MT alone.
JAMA Internal Medicine 12/2013; 174(2). DOI:10.1001/jamainternmed.2013.12855 · 13.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In current international guidelines the recommendation for intra-aortic balloon pump (IABP) use has been downgraded in cardiogenic shock complicating acute myocardial infarction on the basis of registry data. In the largest randomised trial (IABP-SHOCK II), IABP support did not reduce 30 day mortality compared with control. However, previous trials in cardiogenic shock showed a mortality benefit only at extended follow-up. The present analysis therefore reports 6 and 12 month results.
The IABP-SHOCK II trial was a randomised, open-label, multicentre trial. Patients with cardiogenic shock complicating acute myocardial infarction who were undergoing early revascularisation and optimum medical therapy were randomly assigned (1:1) to IABP versus control via a central web-based system. The primary efficacy endpoint was 30 day all-cause mortality, but 6 and 12 month follow-up was done in addition to quality-of-life assessment for all survivors with the Euroqol-5D questionnaire. A masked central committee adjudicated clinical outcomes. Patients and investigators were not masked to treatment allocation. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00491036.
Between June 16, 2009, and March 3, 2012, 600 patients were assigned to IABP (n=301) or control (n=299). Of 595 patients completing 12 month follow-up, 155 (52%) of 299 patients in the IABP group and 152 (51%) of 296 patients in the control group had died (relative risk [RR] 1·01, 95% CI 0·86-1·18, p=0·91). There were no significant differences in reinfarction (RR 2·60, 95% CI 0·95-7·10, p=0·05), recurrent revascularisation (0·91, 0·58-1·41, p=0·77), or stroke (1·50, 0·25-8·84, p=1·00). For survivors, quality-of-life measures including mobility, self-care, usual activities, pain or discomfort, and anxiety or depression did not differ significantly between study groups.
In patients undergoing early revascularisation for myocardial infarction complicated by cardiogenic shock, IABP did not reduce 12 month all-cause mortality.
German Research Foundation; German Heart Research Foundation; German Cardiac Society; Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte; University of Leipzig-Heart Centre; Maquet Cardiopulmonary; Teleflex Medical.
The Lancet 11/2013; 382(9905):1638-1645. DOI:10.1016/S0140-6736(13)61783-3 · 45.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with bicuspid aortic valves (BAVs) are considered a relative contraindication to transcatheter aortic valve implantation (TAVI). One of the main reasons is the presumed risk for residual aortic regurgitation (AR). However, case reports and small case series have suggested that TAVI can be successfully performed with acceptable clinical outcomes in high-risk patients with BAV. Within the large German TAVI Registry, we sought to evaluate TAVI in older high-risk patients with BAV. From January 2009 to June 2010, a total of 1,424 patients with severe aortic stenosis undergoing TAVI were prospectively enrolled into the German TAVI Registry. For the present analysis, patients with valve-in-valve procedures were excluded and those with BAV (n = 38, 3%) were compared with those with tricuspid aortic valve (TAV; n = 1357, 97%). Patient characteristics did not markedly differ and procedural success was very high in both groups. There was a higher rate of relevant AR (≥II) after TAVI among patients with BAV (25 vs 15%, p = 0.05), whereas pacemakers were more often implanted in patients with TAV (17% vs 35%, p = 0.02). Thirty-day mortality rate was similar in both cohorts (11% vs 11%). In a Cox proportional regression analysis, BAV was not associated with higher 1-year mortality rate (hazard ratio 0.64, 95% confidence interval 0.29 to 1.41). In selected patients with BAV, TAVI can be performed with a satisfactory clinical result. Although the risk for relevant AR seems to be greater among patients with BAV, 30-day and 1-year mortality rates were not elevated compared with patients with TAV.
The American journal of cardiology 11/2013; 113(3). DOI:10.1016/j.amjcard.2013.10.023 · 3.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rationale:
High-density lipoprotein (HDL) exerts endothelial-protective effects via stimulation of endothelial cell (EC) nitric oxide (NO) production. This function is impaired in patients with cardiovascular disease. Protective effects of exercise training (ET) on endothelial function have been demonstrated.
This study was performed to evaluate the impact of ET on HDL-mediated protective effects and the respective molecular pathways in patients with chronic heart failure (CHF).
Methods and results:
HDL was isolated from 16 healthy controls (HDL(healthy)) and 16 patients with CHF-NYHA-III (HDL(NYHA-IIIb)) before and after ET, as well as from 8 patients with CHF-NYHA-II (HDL(NYHA-II)). ECs were incubated with HDL, and phosphorylation of eNOS-Ser(1177), eNOS-Thr(495), PKC-βII-Ser(660), and p70S6K-Ser(411) was evaluated. HDL-bound malondialdehyde and HDL-induced NO production by EC were quantified. Endothelial function was assessed by flow-mediated dilatation. The proteome of HDL particles was profiled by shotgun LC-MS/MS. Incubation of EC with HDL(NYHA-IIIb) triggered a lower stimulation of phosphorylation at eNOS-Ser(1177) and a higher phosphorylation at eNOS-Thr(495) when compared with HDL(healthy). This was associated with lower NO production of EC. In addition, an elevated activation of p70S6K, PKC-βII by HDL(NYHA-IIIb), and a higher amount of malondialdehyde bound to HDL(NYHA-IIIb) compared with HDL(healthy) was measured. In healthy individuals, ET had no effect on HDL function, whereas ET of CHF-NYHA-IIIb significantly improved HDL function. A correlation between changes in HDL-induced NO production and flow-mediated dilatation improvement by ET was evident.
These results demonstrate that HDL function is impaired in CHF and that ET improved the HDL-mediated vascular effects. This may be one mechanism how ET exerts beneficial effects in CHF.
Circulation Research 09/2013; 113(12). DOI:10.1161/CIRCRESAHA.113.301684 · 11.02 Impact Factor