Skeletal muscle weakness is related to insulin resistance in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is associated with insulin resistance, indicating impairment in the control of energy metabolism. Insulin resistance in CHF relates to symptomatic status and independently predicts poor prognosis. We sought to determine whether insulin sensitivity is related to skeletal muscle strength in patients with CHF, taking into account muscle size and perfusion. METHODS: Quadriceps muscle size (square centimetre cross-sectional area at mid-femur level, computed tomography), isometric quadriceps muscle strength [absolute (in N) and strength per unit muscle area (N/cm2 )], resting-leg blood flow (plethysmography) and maximal oxygen consumption (treadmill exercise test) were measured in 33 patients with CHF (left ventricular ejection fraction 28 ± 3.2%, mean ± Standard Error of the mean (SEM)) and 20 healthy controls. Insulin sensitivity was assessed by intravenous glucose tolerance tests and minimal modelling analysis. RESULTS: Right quadriceps strength (-27.0%, P < 0.0001), strength per muscle area (-18.0%, P < 0.003) and insulin sensitivity (-64.2%, P < 0.001) were lower in patients with CHF. The correlation between insulin sensitivity and absolute muscle strength was significant in the CHF group (r = 0.54, P = 0.001) and borderline in controls (r = 0.47, P = 0.06). This association remained significant between insulin sensitivity and strength per muscle area (CHF: r = 0.52, P < 0.01; controls: r = 0.62, P < 0.05). In stepwise regression analyses in CHF, only insulin sensitivity emerged as a predictor of strength per unit area of muscle [standardized coefficient (SC) = 0.45, P = 0.006; diuretic dose, SC = -0.31, P = 0.051; R2 = 0.37, P = 0.001], while age, left ventricular ejection fraction, maximal oxygen consumption, fasting glucose and insulin and blood flow were excluded. In controls, only insulin sensitivity remained in the final regression model (SC = 0.62, P = 0.004; R2 = 0.39, P = 0.004). CONCLUSIONS: The myofibril contractile function of the quadriceps, i.e. functional quality of skeletal muscle, is strongly related to insulin sensitivity in patients with CHF and in healthy controls, independently of muscle size. Therapies aimed at improving insulin sensitivity in patients with CHF may clarify whether this relationship is causal.

Intestinal blood flow in patients with chronic heart failure: a link with bacterial growth, gastrointestinal symptoms, and cachexia.

BACKGROUND: Blood flow in the intestinal arteries is reduced in patients with stable heart failure (HF) and relates to gastrointestinal (GI) symptoms and cardiac cachexia. OBJECTIVES: The aims of this study were to measure arterial intestinal blood flow and assess its role in juxtamucosal bacterial growth, GI symptoms, and cachexia in patients with HF. METHODS: A total of 65 patients and 25 controls were investigated. Twelve patients were cachectic. Intestinal blood flow and bowel wall thickness were measured using ultrasound. GI symptoms were documented. Bacteria in stool and juxtamucosal bacteria on biopsies taken during sigmoidoscopy were studied in a subgroup by fluorescence in situ hybridization. Serum lipopolysaccharide antibodies were measured. RESULTS: Patients showed 30% to 43% reduced mean systolic blood flow in the superior and inferior mesenteric arteries and celiac trunk (CT) compared with controls (p < 0.007 for all). Cachectic patients had the lowest blood flow (p < 0.002). Lower blood flow in the superior mesenteric artery and CT was correlated with HF severity (p < 0.04 for all). Patients had more feelings of repletion, flatulence, intestinal murmurs, and burping (p < 0.04). Burping and nausea or vomiting were most severe in patients with cachexia (p < 0.05). Patients with lower CT blood flow had more abdominal discomfort and immunoglobulin A-antilipopolysaccharide (r = 0.76, p < 0.02). Antilipopolysaccharide response was correlated with increased growth of juxtamucosal but not stool bacteria. Patients with intestinal murmurs had greater bowel wall thickness of the sigmoid and descending colon, suggestive of edema contributing to GI symptoms (p < 0.05). In multivariate regression analysis, lower blood flow in the superior mesenteric artery, CT (p < 0.04), and inferior mesenteric artery (p = 0.056) was correlated with the presence of cardiac cachexia. CONCLUSIONS: Intestinal blood flow is reduced in patients with HF. This may contribute to juxtamucosal bacterial growth and GI symptoms in patients with advanced HF complicated by cachexia.

Non-invasive assessment of cardiac hemodynamics in patients with advanced cancer and with chronic heart failure: a pilot feasibility study.

INTRODUCTION: Relationships between cardiac pressure and volume have been suggested as markers of cardiac contractility; parameters include stroke work and the maximal rate of pressure rise during isovolumic contraction (dP/dtmax). Patients with cancer often display dyspnea and fatigue. These are also frequent symptoms in patients with chronic heart failure (HF). The reasons for similar symptoms in cancer patients are unknown. Using the novel Nexfin Finapres technique, we sought to assess measures of cardiac performance in patients with cancer and compare these values with those from control subjects and patients with chronic HF. MATERIAL AND METHODS: We prospectively studied 98 patients (control n = 18, chronic HF n = 37, advanced pancreatic or colorectal cancer n = 43) and assessed blood pressure (BP), stroke volume (SV), cardiac output (CO), and dP/dtmax at rest. RESULTS: All parameters of interest could be assessed using the Nexfin Finapres technique with SV and CO being significantly higher in patients with cancer than in controls (both p < 0.05). The SV was significantly higher in patients with chronic HF than in controls (p < 0.05). In patients with cancer, SV correlated with age (r = -0.45, p < 0.01) and body weight (r = +0.55, p = 0.0001). In chronic HF, SV declined with increasing age (r = -0.49, p < 0.01); in control subjects, SV increased with increasing body weight (r = +0.57, p = 0.01). CONCLUSIONS: Patients with cancer tended to display elevated BP, CO, SV, and dP/dtmax as compared to control subjects and patients with HF. These findings may reveal an elevated risk for cardiovascular diseases in this group.

EURObservational Research Programme: regional differences and 1-year follow-up results of the Heart Failure Pilot Survey (ESC-HF Pilot).

AIMS: The ESC-HF Pilot survey was aimed to describe clinical epidemiology and 1-year outcomes of outpatients and inpatients with heart failure (HF). The pilot phase was also specifically aimed at validating structure, performance, and quality of the data set for continuing the survey into a permanent Registry. METHODS: The ESC-HF Pilot study is a prospective, multicentre, observational survey conducted in 136 Cardiology Centres in 12 European countries selected to represent the different health systems across Europe. All outpatients with HF and patients admitted for acute HF on 1 day per week for eight consecutive months were included. From October 2009 to May 2010, 5118 patients were included: 1892 (37%) admitted for acute HF and 3226 (63%) patients with chronic HF. The all-cause mortality rate at 1 year was 17.4% in acute HF and 7.2% in chronic stable HF. One-year hospitalization rates were 43.9% and 31.9%, respectively, in hospitalized acute and chronic HF patients. Major regional differences in 1-year mortality were observed that could be explained by differences in characteristics and treatment of the patients. CONCLUSION: The ESC-HF Pilot survey confirmed that acute HF is still associated with a very poor medium-term prognosis, while the widespread adoption of evidence-based treatments in patients with chronic HF seems to have improved their outcome profile. Differences across countries may be due to different local medical practice as well to differences in healthcare systems. This pilot study also offered the opportunity to refine the organizational structure for a long-term extended European network.

Improved insulin sensitivity by the angiotensin receptor antagonist irbesartan in patients with systolic heart failure: a randomized double-blinded placebo-controlled study.

BACKGROUND: Impaired insulin sensitivity is common in patients with chronic systolic heart failure (CHF) and contributes to symptomatic status and impaired prognosis. A specific metabolic effect to improve insulin sensitivity in diabetic patients has been reported for some but not all angiotensin II-receptor antagonists. We aimed to test the ancillary metabolic effect of irbesartan on insulin sensitivity in patients with CHF. METHODS AND PARTICIPANTS: In this placebo-controlled double-blinded study 36 non-diabetic patients with stable ischemic CHF (age 63 ± 9 years, peak VO(2) 16.6 ± 4.8 ml/kg/min, LVEF 32 ± 9%) were randomized to irbesartan 300 mg/d vs placebo on top of standard CHF therapy. Body composition (dual energy X-ray absorptiometry), clinical status, peripheral vasodilator capacity (plethysmography) and neuroendocrine and metabolic profiles were assessed. Primary endpoint was the change of whole body insulin sensitivity after 4 months of treatment assessed by intravenous glucose tolerance testing and minimal modeling. RESULTS: Insulin sensitivity improved by 26% (p<0.001) in the irbesartan group, but not in the placebo group (treatment effect: 1.044 min(-1)·µU·ml(-1)·10(4); 95%CI 0.45 to 1.64, p=0.0026). Treatment effects on systolic and diastolic blood pressure were -11 (95%CI -21 to -1)mmHg and -8 (95%CI -15 to -3)mmHg, respectively. Peripheral vasodilator capacity improved by 14% (p=0.016). Change in insulin sensitivity correlated with increased vasodilator capacity (R=0.47, p=0.021). Body composition and clinical status were not different after 4 months of therapy. Also adiponectin, resistin, cytokine profile, and asymmetric dimethylarginine (ADMA) were not changed after this short-term intervention. CONCLUSION: Therapy with irbesartan improved insulin sensitivity in patients with chronic heart failure. Improved peripheral vasodilator capacity may contribute to the metabolic effect. (Clinical trials identifier: NCT00347087).

Risk stratification in patients with chronic heart failure based on metabolic-immunological, functional and haemodynamic parameters.

BACKGROUND: A vast array of parameters has been proposed to predict mortality in chronic heart failure (CHF). Their applicability into clinical practice remains challenging due to economical and availability considerations. METHODS AND RESULTS: We studied serum uric acid, total cholesterol, and soluble tumour necrosis factor receptor 1 (sTNF-R1) in 114 CHF patients (63.0 ± 1.0 years, NYHA functional class I/II/III/IV: 11/34/54/15) recruited prospectively into a metabolic study program. All patients underwent assessment of left ventricular ejection fraction and measurement of peak oxygen consumption (pVO(2)). Patients were followed for 24 months or until death. A total of 31 patients died; cumulative survival was 78% (95% confidence interval [CI] 70-86%) and 73% (65-81%) at 12 and 24 months, respectively. In single predictor Cox proportional hazard analysis, uric acid, pVO2, sTNFR-1, LVEF (all p<0.0001) and cholesterol (p<0.02) all predicted survival. All parameters remained significant predictors of death after multivariable adjustment (all p<0.02). Receiver-operator characteristic (ROC) curve analyses showed that uric acid and sTNF-R1 are equally strong with regards to their prognostic performance in CHF like pVO(2,) but even better than LVEF. The combination of pVO(2), LVEF, uric acid, and sTNF-R1 in ROC statistics turned out as the best model with the highest prognostic value in CHF (AUC: 0.91, sensitivity: 90.4, specificity: 74.2, p=0.0001). CONCLUSION: Including metabolic-immunological parameters into risk assessment might result in a better risk stratification than modeling based on clinical parameters alone, probably due to a better reflection of CHF as multisystem disease. We suggest metabolic-immunological parameters to be tested in larger populations.

Studies on bacterial endotoxin and intestinal absorption function in patients with chronic heart failure.

BACKGROUND: Small intestinal function may be altered in decompensated chronic heart failure (CHF) and translocating LPS may contribute to systemic inflammation observed in CHF. METHODS: We measured intestinal permeability (melibiose and rhamnose), active (3-O-methyl-d-glucose (3-OMG)) and passive (d-xylose) carrier-mediated absorption in 20 CHF patients (12 edematous and 8 non-edematous) and 8 controls by saccharide absorption technique assessing urinary recovery of orally administered sugars. We additionally measured LPS concentrations in 42 patients with decompensated heart failure and after recompensation. RESULTS: CHF patients had a 54% reduction of active carrier-mediated intestinal transport compared to controls (p<0.0001). This reduction was strongest in edematous compared to non-edematous patients and controls (recovery in urine: 13.2±2.0% vs. 20.8±2.4% vs. 36.0 ± 3.7%, all p ≤ 0.05). Patients showed a 34% reduction of passive carrier-mediated transport, strongest in edematous patients (p=0.006). A greater impairment of active carrier-mediated transport remained significant after adjustment for non-mucosal factors in CHF (p=0.0004). Non carrier-mediated intestinal permeability was not altered. Data from 42 decompensated patients showed a decrease in LPS after recompensation (p=0.004). Edematous patients had highest blood concentrations of LPS, TNF and sTNF-R1 (p<0.04). CHF patients with abnormal LPS concentrations >0.50EU/mL (n=7) had the highest concentrations of TNF (7.0 ± 1.6 vs. 3.1 ± 0.3pg/mL, p<0.02), and sTNF-R1 (3499 ± 52 vs. 1599±219 pg/mL, p=0.02). CONCLUSION: Active carrier-mediated intestinal transport is reduced in decompensated CHF indicating epithelial dysfunction possibly as a consequence of intestinal ischemia. Higher LPS concentrations in edematous CHF relate to inflammation. LPS decreased after recompensation. This suggests a cause/effect relationship between edematous gut wall, epithelial dysfunction and translocating LPS.

Impaired mobilization of CD133(+) bone marrow-derived circulating progenitor cells with an increased number of diseased coronary arteries in ischemic heart disease patients with diabetes.

BACKGROUND: The influence of the number of diseased coronary arteries on the mobilization of CD133/45(+) bone marrow-derived circulating progenitor cells (BM-CPCs) in peripheral blood (PB) in patients with ischemic heart disease (IHD) was analyzed. METHODS AND RESULTS: Mobilization of CD133/45(+) BM-CPCs by flow cytometry was measured in 120 patients with coronary 1 vessel (IHD1, n=40), coronary 2 vessel (IHD2, n=40), and coronary 3 vessel disease (IHD3, n=40), and in a control group (n=40). The mobilization of CD133/45(+) BM-CPCs was significantly reduced in patients with IHD compared to the control group (P<0.001). The mobilization of CD133/45(+) BM-CPCs was impaired in patients with IHD3 compared to IHD1 (P<0.001) and to IHD2 (P<0.001). But there was no significant difference in mobilization of CD133/45(+) BM-CPCs between the patients with IHD2 and IHD1 (P=0.35). Moreover, we found significantly reduced CD133/45(+) cell mobilization in patients with a high SYNTAX-Score (SS) compared to a low SS (P<0.001) and an intermediate SS (P<0.001). In subgroup analyzes, we observed a significantly negative correlation between levels of hemoglobin A(1c) and the mobilization of CD133/45(+) BM-CPCs (P=0.001, r=-0.6). CONCLUSIONS: The mobilization of CD133/45(+) BM-CPCs in PB is impaired in patients with IHD. This impairment might augment with increased number of diseased coronary arteries. Moreover, mobilization of CD133/45(+) BM-CPCs in ischemic tissue is further impaired by diabetes in patients with IHD.

Improvement of cardiac function by intracoronary freshly isolated bone marrow cells transplantation in patients with acute myocardial infarction.

BACKGROUND: We analyzed in the present study the influence of intracoronary autologous freshly isolated bone marrow cells transplantation (BMCs-Tx) on cardiac function in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: The 32 patients with AMI were enrolled in this prospective nonrandomized study to either freshly isolated BMC-Tx or to a control group without cell therapy. Global left ventricular ejection fraction (LVEF) and the size of infarct area were determined by left ventriculography. We observed in patients with autologous freshly isolated BMCs-Tx at 6 months follow up a significant reduction of infarct size as compared to control group. Moreover, we found a significant increase of LVEF as well as infarct wall movement velocity at 6 months follow up in cell therapy group as compared to control group. In the control group there was no significant difference of LVEF, infarct size and infarct wall movement velocity between baseline and 6 months after AMI. CONCLUSIONS: These results demonstrate for the first time that intracoronary transplantation of autologous freshly isolated BMCs by use of a point of care system is safe, and may lead to improvement of cardiac function in patients with AMI.

Usefulness of minimal modelling to assess impaired insulin sensitivity in patients with chronic heart failure.

BACKGROUND: In chronic heart failure (CHF), impaired insulin sensitivity (Si) is frequently observed. It is associated with symptomatic status and poor prognosis suggesting an intrinsic role of Si within CHF pathophysiology. HOmeostasis Model Assessment (HOMA), Fasting Insulin Resistance Index (FIRI), and QUick Insulin CheCK Index (QUICKI) are based on single-time fasting glucose and insulin assessment. Their value and discriminatory power in comparison to dynamic range assessment of Si by minimal modelling are not well established. METHODS AND RESULTS: In 105 patients with stable CHF (mean age 62 ± 1 years, peak VO(2) 18.2 ± 0.7 mL/kg/min, LVEF 28 ± 2%, mean ± SEM) Si was assessed by minimal modelling. HOMA, FIRI, and QUICKI were calculated from single-time point fasting glucose and insulin measurements. Detailed body composition was analyzed using dual-energy X-ray absorptiometry. All assessment methods showed impaired Si in CHF patients compared to healthy controls (n = 25). Yet, only minimal model-derived Si differentiated between NYHA classes (p = 0.0007). Further, minimal modelling was the only method to be directly associated with peak oxygen uptake and skeletal muscle strength. Model-derived Si predicted survival independently of established prognostic markers in CHF (RR 0.30 [95%CI 0.14-0.63]; p = 0.0016). In contrast, HOMA, FIRI and QUICKI did not show any of these qualities. CONCLUSION: HOMA, FIRI and QUICKI are surrogate estimates of Si with reduced discriminatory power in patients with CHF. While they are suitable to semi-quantitatively categorize impaired Si compared to normal values, the dynamic range assessment of Si by minimal modelling is superior for quantitative assessment of Si in pathophysiological studies.

Long-term survival of routine implantable cardioverter/defibrillator recipients appears to be significantly impaired with concomitant diuretics and improved with aldosterone antagonists.

Evidence-based treatment for heart failure (HF) comprises beta-blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone receptor antagonists (ARA). Diuretics (DR) are prescribed in acute and chronic HF, but their impact on survival and ventricular tachyarrhythmias (VT/VF) is unclear. The present observational study aims to examine the influence of DR and ARA on survival and appropriate cardioverter/defibrillator (ICD) treatment episodes in routine ICD patients. In 352 consecutive ICD patients (291 men, 60 ± 12 years, LVEF 34 ± 15%, follow-up 37 ± 19 months) overall survival and the time to a first appropriate VT/VF episode were assessed. Electrograms were validated. Potassium and creatinine serum levels and the medical treatment regimen for heart failure were documented at baseline. Multivariate Cox regression analyses revealed significantly worse survival for patients with DR compared to those without DR (OR 0.24, CI 0.08-0.76, P= 0.016), whereas the group with ARA had better survival compared to patients without (OR 2.05, CI 1.02-4.10, P= 0.04). Patient groups did not differ regarding survival without incident VT/VF (DR+ vs. DR- OR 1.10, CI 0.67-1.83, P= 0.70; OR 0.66, CI 0.40-1.09, P= 0.10). Long-term survival appears to be compromised in ICD patients receiving concomitant DR, but is favorably influenced by ARA, although VT/VF incidence does not differ. Randomized analyses are warranted to assess long-term prognostic effects of DR in HF.

Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology.

The reductions in mortality and morbidity being achieved among cancer patients with current therapies represent a major achievement. However, given their mechanisms of action, many anti-cancer agents may have significant potential for cardiovascular side effects, including the induction of heart failure. The magnitude of this problem remains unclear and is not readily apparent from current clinical trials of emerging targeted agents, which generally under-represent older patients and those with significant co-morbidities. The risk of adverse events may also increase when novel agents, which frequently modulate survival pathways, are used in combination with each other or with other conventional cytotoxic chemotherapeutics. The extent to which survival and growth pathways in the tumour cell (which we seek to inhibit) coincide with those in cardiovascular cells (which we seek to preserve) is an open question but one that will become ever more important with the development of new cancer therapies that target intracellular signalling pathways. It remains unclear whether potential cardiovascular problems can be predicted from analyses of such basic signalling mechanisms and what pre-clinical evaluation should be undertaken. The screening of patients, optimization of therapeutic schemes, monitoring of cardiovascular function during treatment, and the management of cardiovascular side effects are likely to become increasingly important in cancer patients. This paper summarizes the deliberations of a cross-disciplinary workshop organized by the Heart Failure Association of the European Society of Cardiology (held in Brussels in May 2009), which brought together clinicians working in cardiology and oncology and those involved in basic, translational, and pharmaceutical science.

Improved mobilization of the CD34(+) and CD133(+) bone marrow-derived circulating progenitor cells by freshly isolated intracoronary bone marrow cell transplantation in patients with ischemic heart disease.

Cell therapy is a promising novel option for treatment of cardiovascular disease. Because the role of bone marrow-derived circulating progenitor cells (BM-CPCs) after cell therapy is less clear, we analyzed in this randomized, controlled study the influence of intracoronary autologous freshly isolated bone marrow cell transplantation (BMC-Tx) by using a point-of-care system on cardiac function and on the mobilization of BM-CPCs in patients with ischemic heart disease (IHD). Fifty-six patients with IHD were randomized to either receive freshly isolated BMC-Tx or a control group that did not receive cell therapy. Peripheral blood concentrations of CD34/45(+) and CD133/45(+) CPCs were measured by flow cytometry pre-, immediately post-, and at 3, 6, and 12 months postprocedure in both groups. Global ejection fraction and the size of infarct area were determined by left ventriculography. We observed in patients with IHD after intracoronary transplantation of autologous freshly isolated BMCs-Tx at 3 and 12 months follow-up a significant reduction of the size of infarct area and increase of global ejection fraction as well as infarct wall movement velocity. The mobilization of CD34/45(+) and CD133/45(+) BM-CPCs significantly increased at 3, 6, and 12 months after cell therapy when compared with baseline in patients with IHD, although no significant changes were observed between pre- and immediately postintracoronary cell therapy administration. In the control group without cell therapy, there was no significant difference of CD34/45(+) and CD133/45(+) BM-CPCs mobilization between pre- and at 3, 6, and 12 months postcoronary angiography. Intracoronary transplantation of autologous freshly isolated BMCs by using a point-of-care system in patients with IHD may enhance and prolong the mobilization of CD34/45(+) and CD133/45(+) BM-CPCs in peripheral blood and this might increase the regenerative potency in IHD.

EURObservational Research Programme: the Heart Failure Pilot Survey (ESC-HF Pilot).

AIMS: The primary objective of the new ESC-HF Pilot Survey was to describe the clinical epidemiology of outpatients and inpatients with heart failure (HF) and the diagnostic/therapeutic processes applied across 12 participating European countries. This pilot study was specifically aimed at validating the structure, performance, and quality of the data set, for continuing the survey into a permanent registry. METHODS AND RESULTS: The ESC-HF Pilot study is a prospective, multicentre, observational survey conducted in 136 cardiology centres from 12 European countries selected to represent the different health systems and care attitudes across Europe. All outpatients with HF and patients admitted for acute HF were included during the enrolment period (1 day per week for 8 consecutive months). From October 2009 to May 2010, 5118 patients were included in this pilot survey, of which 1892 (37%) were admitted for acute HF and 3226 (63%) for chronic HF. Ischaemic aetiology was reported in about half of the patients. In patients admitted for acute HF, the most frequent clinical profile was decompensated HF (75% of cases), whereas pulmonary oedema and cardiogenic shock were reported, respectively, in 13.3 and 2.3% of the cases. The total in-hospital mortality rate was 3.8% and was cardiovascular in 90.1% of the cases. Lowest and highest mortality rates were observed in hypertensive HF and in cardiogenic shock, respectively. More than 80% of patients with chronic HF were treated with renin-angiotensin-aldosterone system blockers and ß-adrenergic blockers. However, target doses of such drugs were reached in one-third to one-fourth of the patients only. CONCLUSION: The ESC-HF Pilot Survey is an example of the possibility of utilizing an observational methodology to get insights into the current clinical practice in Europe, whose picture will be completed by the 1-year follow-up. Moreover, this study offered the opportunity to refine the organizational structure of a long-term, extended European network.

The impact of impaired renal function on mortality in patients with acutely decompensated chronic heart failure.

AIMS: Acute heart failure syndromes, commonly recognized as de novo heart failure or acute decompensated chronic heart failure (ADHF), are characterized by a rapid onset or change in signs and symptoms of heart failure requiring urgent treatment. Coexisting renal dysfunction is associated with poor prognosis in these patients. We sought to determine whether renal impairment in particular and other admission factors in general predict long-term mortality after hospitalization for ADHF. METHODS AND RESULTS: We studied 128 patients (age 63 + or - 12 years, 76% male) in NYHA class 2.6 + or - 0.7 with a left ventricular ejection fraction (LVEF) < or = 39%, hospitalized due to ADHF. Mortality rates (per 100 person-years) were 21.9 at 12 months and 12.0 at 60 months. We found that admission serum creatinine level was the best predictor of mortality after 1 (P < 0.001, log-transformed due to skewed distribution) and 5 years (P = 0.001), followed by creatinine clearance, the use of loop diuretics, and digoxin. Moreover, higher NYHA class, decreased body mass index (BMI) and increased levels of urea predicted 1 and 5 years mortality on univariate analysis. In the multivariate analysis, creatinine, NYHA class, and LVEF emerged as independent predictors of mortality after 1 year, whereas BMI and the use of diuretics did not reach significance (joint chi(2) = 29.40, P < 0.001). After 5 years, creatinine and NYHA class independently predicted all-cause mortality (joint chi(2) = 22.71, P < 0.001), but BMI and age did not remain significant. CONCLUSION: Admission creatinine level strongly predicts medium- and long-term mortality after hospitalization in patients with ADHF, and serves as a cheap and fast clinical marker to identify patients at risk of death.

Indication for percutaneous aortic valve implantation.

The incidence of valvular aortic stenosis has increased over the past decades due to improved life expectancy. Surgical aortic valve replacement is currently the only treatment option for severe symptomatic aortic stenosis that has been shown to improve survival. However, up to one third of patients who require lifesaving surgical aortic valve replacement are denied surgery due to high comorbidities resulting in a higher operative mortality rate. In the past such patients could only be treated with medical therapy or percutaneous aortic valvuloplasty, neither of which has been shown to improve mortality. With advances in interventional cardiology, transcatheter methods have been developed for aortic valve replacement with the goal of offering a therapeutic solution for patients who are unfit for surgical therapy. Currently there are two catheter-based treatment systems in clinical application (the Edwards SAPIEN aortic valve and the CoreValve ReValving System), utilizing either a balloon-expandable or a self-expanding stent platform, respectively.

Endovascular repair of thoracic aortic aneurysm.

A thoracic aortic aneurysm (TAA) is a potentially life-threatening condition with structural weakness of the aortic wall, which can progress to arterial dilatation and rupture. Today, both an increasing awareness of vascular disease and the access to tomographic imaging facilitate the diagnosis of TAA even in an asymptomatic stage. The risk of rupture for untreated aneurysms beyond a diameter of 5.6 cm ranges from 46% to 74% and the two-year mortality rate is greater than 70%, with most deaths resulting from rupture. Treatment options include surgical and non-surgical repair to prevent aneurysm enlargement and rupture. While most cases of ascending aortic involvement are subject to surgical repair (partially with valve-preserving techniques), aneurysm of the distal arch and descending thoracic aorta are amenable to emerging endovascular techniques as an alternative to classic open repair or to a hybrid approach (combining debranching surgery with stent grafting) in an attempt to improve outcomes.

Diabetes mellitus, cachexia and obesity in heart failure: rationale and design of the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF).

BACKGROUND: Chronic heart failure (CHF) is increasing in prevalence. Patients with CHF usually have co-morbid conditions, but these have been subjected to little research and consequently there is a paucity of guidance on how to manage them. Obesity and diabetes mellitus are common antecedents of CHF and often complicate management and influence outcome. Cachexia is an ominous and often missed sign in patients with CHF. METHODS: This manuscript describes the rationale and the design of Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF), a prospective, multicentre, multinational, longitudinal, pathophysiological evaluation study, which is being conducted in 11 centres across six countries in the European Union and in Russia. We aim to recruit >1,600 patients with CHF due to various common aetiologies, irrespective of left ventricular ejection fraction, and with or without co-morbidities at study entry. In addition, >300 patients with type 2 diabetes mellitus without CHF and >150 healthy subjects will serve as control groups. Participants will be systematically investigated at annual intervals for up to 48 months. Additional investigations focusing on cellular and subcellular mechanisms, adipose and skeletal muscle tissue, and in endothelial progenitor cells will be performed in selected subgroups. CONCLUSIONS: SICA-HF will provide insights into common co-morbidities in CHF with a specific emphasis on diabetes mellitus and body mass. This will provide a more thorough pathophysiological understanding of the complexity of CHF that will help develop therapies tailored to manage specific co-morbidities.

A network against failing hearts--introducing the German "Competence Network Heart Failure".

Heart failure (HF) has been identified as one of the most threatening diseases for the western civilisation, posing a risk to health for a rising number of patients. Acknowledging the medical problem of HF to be both economically and socially threatening the German Federal Ministry of Research and Education (BMBF) initiated a nationwide research network aiming to find new ways in prevention, alleviation and treatment of the widespread disease. The "Competence Network Heart Failure" (CNHF), initiated in 2003, bundles the scientific expertise in a large-scale research network; its aims are the coordination of basic and applied clinical research as well as dissemination of findings into clinical practice in order to consolidate and perpetuate the achieved improvements. The scope of this paper is to introduce the CNHF and to provide an overview of the tasks and hitherto attained achievements to a broad spectrum of health care providers.