Long-Term Technical Performance of the Osypka QT-5® Ventricular Pacemaker Lead.

BACKGROUND: Lead-associated complications and technical issues in patients with cardiac implantable electronic devices are common but underreported in the literature. METHODS: All patients undergoing implantation of the Osypka QT-5® ventricular lead at the University Clinic St. Pölten between 1 January 2006 and 31 December 2012 were retrospectively analyzed (n = 211). Clinical data including pacemaker follow-up examinations and the need for lead revisions were assessed. Kaplan-Meier analysis to estimate the rate of lead dysfunction during long-term follow-up was conducted. RESULTS: Patients were followed for a median of 5.2 years (interquartile range (IQR) 2.0-8.7). R-wave sensing properties at implantation, compared to last follow-up, remained basically unchanged: 9.9 mV (IQR 6.8-13.4) and 9.6 mV (IQR 5.6-12.0), respectively). Ventricular pacing threshold significantly increased between implantation (0.5 V at 0.4 ms; IQR 0.5-0.8) and the first follow-up visit (1.0 V at 0.4 ms; IQR 0.8-1.3; p < 0.001) and this increase persisted throughout to the last check-up (0.9 V at 0.4 ms; IQR 0.8-1.2). Impedance significantly declined from 1142 Ω (IQR 955-1285) at implantation to 814 Ω (IQR 701-949; p < 0.001) at the first check-up, followed by a further decrease to 450 Ω (IQR 289-652; p < 0.001) at the last check-up. Overall, the Osypka QT-5® ventricular lead was replaced in 36 patients (17.1%). CONCLUSIONS: This report shows an unexpected high rate of technical issues of the Osypka QT-5® ventricular lead during long-term follow-up.

Curriculum heart failure : Task force curriculum heart failure of the working group on heart failure of the Austrian Cardiological Society.

It is well recognized that organized management of heart failure patients, including care by heart failure specialists, improves outcomes of these patients. In response to this, the Heart Failure Association of the European Society of Cardiology proposed a basic framework of a heart failure curriculum, which became a blueprint for training programs across Europe. The present curriculum for heart failure was well coordinated with the version issued by the German Society for Cardiology in order to achieve good comparability. Training in this Austrian curriculum takes two years, during which the predominant activity focuses on the care of patients with heart failure. The first year includes general (basic) training, while in the second year special modules (advanced chronic and acute heart failure with specific treatment, device treatment, interventional heart failure treatment, outpatient care or rehabilitation, heart failure diagnostics) must be chosen that impart in-depth knowledge, experience and/or skills. Of the five offered modules two must be completed for 6 months each. At least one specialist in internal medicine and cardiology with the additional qualification of heart failure must act as a supervisor at the training center. A certified Heart Failure Unit or a comparable structure should be available at the training center and integrated into the clinical routine of the cardiology department. Applications for recognition of curricular achievements in order to obtain the additional qualification "heart failure specialist" shall be evaluated by a dedicated committee of the nucleus of the Heart Failure Working Group of the Austrian Cardiological Society. The candidate will receive recognition of the additional qualification in heart failure, issued by the Austrian Cardiological Society.

Indications for and outcome in patients with the wearable cardioverter-defibrillator in a nurse-based training programme: results of the Austrian WCD Registry.

BACKGROUND: The wearable cardioverter-defibrillator is a treatment option for patients at temporarily high risk of sudden cardiac death or in whom implantation of a cardioverter-defibrillator is temporarily not possible. OBJECTIVES: The aim of this study was to provide real-world data on patients receiving this therapy in a nurse-based wearable cardioverter-defibrillator training programme. METHODS: A registry including all patients prescribed with a wearable cardioverter-defibrillator in Austria between 2010 and 2016. Overall, 448 patients received a wearable cardioverter-defibrillator in 48 centres. Patients received structured nurse-based wearable cardioverter-defibrillator educational initial training followed by remote monitoring. RESULTS: Main indications were: severe non-ischaemic cardiomyopathy (21%); recent myocardial infarction and percutaneous coronary intervention (20%); and stable coronary artery disease with percutaneous coronary intervention/coronary artery bypass grafting (14%). Eleven patients (2.5%) received 22 appropriate wearable cardioverter-defibrillator shocks. Two patients (0.4%) received three inappropriate shocks. The risk of sudden cardiac death varied between different aetiologies. Eight out of 11 (73%) patients received their first wearable cardioverter-defibrillator shock within 30 days. The main reasons for termination of the wearable cardioverter-defibrillator therapy were implantable cardioverter-defibrillator implantation (55.5%) and improvement of left ventricular ejection fraction to more than 35% (33%). CONCLUSION: The wearable cardioverter-defibrillator is an effective and safe treatment option in patients at either transiently elevated risk of ventricular tachycardia/ventricular fibrillation or mandated postponed implantable cardioverter-defibrillator implantation, with a 2.5% shock rate over a median 54 days wearable cardioverter-defibrillator treatment period. However, both the wearable cardioverter-defibrillator shock rate and implantable cardioverter-defibrillator implantation rate vary widely depending on the wearable cardioverter-defibrillator indication. Nurse-based wearable cardioverter-defibrillator training is associated with high patient adherence, with a median wearing duration per day of 23.5 (1-24) hours.

Specific indications and clinical outcome in patients with subcutaneous implantable cardioverter-defibrillator (ICD) - A nationwide multicentre registry.

BACKGROUND: Subcutaneous implantable cardioverter-defibrillators (S-ICD) are an innovative and less invasive alternative to transvenous ICD (TV-ICD) in selected patients. We aimed to investigate the underlying diseases and the specific indications for implanting S-ICD in clinical practice, as well as the prevalence of shock delivery and complications. METHODS AND RESULTS: From December 2012, data of 236 patients (30,5% female; age 48,6±16,8years) were gathered from 12 centres in Austria. Follow-up data over a period of 1,7±1,1years were available for 231 patients (in total 359,2 patient-years). Predominant underlying diseases were ischemic cardiomyopathy (iCMP; 32,0%), idiopathic ventricular fibrillation (22,6%) and dilated cardiomyopathy (dCMP; 17,3%). The most frequent indications for implantation were sudden cardiac death survival (27,4%), primary prevention for iCMP (23,9%) and for dCMP (12,8%), and previous explantation of TV-ICD (12,4%). Appropriate shocks were documented in 16 patients (6,9%), iCMP being the predominant underlying disease. Arrhythmia conversion was successful in all patients, efficacy of the first shock was 96%. Inappropriate shock rate was 5,2%, predominantly caused by oversensing of T wave or artefacts. A device upgrade to an ICD system with pacing function was necessary in <1%. Clinical complications needing surgical revision occurred in 8 patients (3,5%). CONCLUSIONS: S-ICD were mostly implanted for primary prevention, one fourth of our cases were sudden death survivors. Clinical and functional complication rate was relatively low. In conclusion, S-ICD is a safe and efficient alternative in a larger population of ICD candidates, when no cardiac pacing is needed. EC-number: C-136-17.

Soluble Urokinase-Type Plasminogen Activator Receptor Improves Risk Prediction in Patients With Chronic Heart Failure.

OBJECTIVES: This study investigated the predictive value of soluble urokinase-type plasminogen activator receptor (suPAR) in patients with chronic heart failure (CHF). BACKGROUND: SuPAR originates from proteolytic cleavage of the membrane-bound receptor from activated immune and endothelial cells and reflects the level of immune activation. As inflammation plays a crucial role in the complex pathophysiology of CHF, we hypothesized that suPAR might be a suitable prognostic biomarker in patients with CHF. METHODS: SuPAR levels were determined in 319 patients with CHF admitted to our outpatient department for heart failure and in a second cohort consisting of 346 patients with CHF, for validation. RESULTS: During a median follow-up time of 3.2 years, 119 patients (37.3%) died. SuPAR was a strong predictor of mortality with a crude hazard ratio (HR) per increase of 1 SD (HR per 1 SD) of 1.96 (95% confidence interval [CI]: 1.63 to 2.35; p < 0.001) in univariate analysis and remained significant after comprehensive multivariate adjustment with an adjusted HR per 1 SD of 1.38 (95% CI: 1.04 to 1.83; p = 0.026). SuPAR added prognostic value beyond the multivariate model indicated by improvements in C-statistics (area under the curve: 0.72 vs 0.74, respectively; p = 0.02), the category-free net reclassification index (24.9%; p = 0.032), and the integrated discrimination improvement (0.011; p = 0.05). Validation in the second cohort yielded consistent results. CONCLUSIONS: SuPAR is a strong and independent predictor of mortality in patients with CHF, potentially suitable to refine risk assessment in this vulnerable group of patients. Our results emphasize the impact of immune activation on survival in patients with CHF.

Clusterin/apolipoprotein J is independently associated with survival in patients with chronic heart failure.

BACKGROUND: Clusterin/apolipoprotein J (CLU) is a ubiquitous expressed glycoprotein with cytoprotective properties capable to prevent myocardial injury in experimental studies. We hypothesized that decreasing levels of CLU might be involved in progression of chronic heart failure (HF) and therefore represent a potential biomarker for prognosis in this vulnerable group of patient. OBJECTIVE: We aimed to determine the prognostic value of plasma CLU in patients with HF. METHODS: Plasma CLU levels were determined in a prospectively recruited cohort comprising 318 patients with chronic HF and validated in a second cohort comprising 346 patients with advanced HF. RESULTS: During a median follow-up time of 3.2 years (interquartile range 2.0-4.9), 119 patients (37.3%) deceased including 83 patients (26.1%), who died from cardiovascular events. CLU was an inverse predictor of mortality with a crude hazard ratio (HR) per increase of 1 standard deviation (1 SD) of 0.75 (95% confidence interval [CI]: 0.62 to 0.9, P = .002) and specifically cardiovascular mortality with an HR per 1 SD of 0.67 (95% CI: 0.53-0.84, P < .001). CLU remained significantly associated with cardiovascular mortality after comprehensive adjustment for established HF-related risk factors and potential confounders with an adjusted HR per 1 SD of 0.79 (95% CI: 0.63-0.99, P = .042). Validation in the second cohort yielded similar results and confirmed CLU as independent prognosticator in patients with chronic HF. CONCLUSION: Our results point toward an ongoing consumption of CLU involved in the complex pathophysiology of HF and suggest CLU as novel and promising biomarker for prognosis in patients with chronic HF.

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.

A multi-biomarker risk score improves prediction of long-term mortality in patients with advanced heart failure.

BACKGROUND: Accurate risk prediction is important for an adequate management of heart failure (HF) patients. We assessed the incremental prognostic ability of a multi-biomarker approach in advanced HF. METHODS: In 349 patients with advanced HF (median 75 years, 66% male) we investigated the incremental prognostic value of 12 novel biomarkers involved in different pathophysiological pathways including inflammation, immunological activation, oxidative stress, cell growth, remodeling, angiogenesis and apoptosis. RESULTS: During a median follow-up of 4.9 years 55.9% of patients died. Using multivariable Cox regression and bootstrap variable-selection age, chronic obstructive pulmonary disease, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the following 5 novel biomarkers were retained in the best mortality prediction model: the chemokine fractalkine, the angiogenic and mitogenic hepatocyte growth factor (HGF), the growth differentiation factor 15 (GDF-15) influencing cardiac remodeling and apoptosis, and the 2 pro-apoptotic molecules soluble apoptosis-stimulating fragment (sFAS) and soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL). This multi-biomarker score had strong discriminatory power for 5-year mortality (area under the Receiver Operating Characteristic curve [AUC]=0.81) and improved risk prediction beyond the prognostic power of a comprehensive conventional risk score including known clinical predictors and NT-proBNP (AUC=0.77). Net reclassification confirmed a significant improvement of individual risk prediction (p=0.003). CONCLUSIONS: Risk prediction by a multi-biomarker score is superior to a conventional risk score including clinical parameters and NT-proBNP. Additional predictive information from different biological pathways reflects the multisystemic character of HF.

Fractalkine is an independent predictor of mortality in patients with advanced heart failure.

Immunological processes are implicated in the multifactorial pathophysiology of heart failure (HF). The multifunctional chemokine fractalkine (CX3CL1) promotes the extravasation of cytotoxic lymphocytes into tissues. We aimed to assess the prognostic value of fractalkine in HF. Fractalkine plasma levels were determined in 349 patients with advanced systolic HF (median 75 years, 66% male). During a median follow-up of 4.9 years (interquartile range: 4.6-5.2), 55.9% of patients died. Fractalkine was a significant predictor of all-cause mortality (p<0.001) with a hazard ratio of 2.78 (95% confidence interval: 1.95-3.95) for the third compared to the first tertile. This association remained significant after multivariable adjustment for demographics, clinical predictive variables and N-terminal pro-B-type natriuretic peptide (NT-proBNP, p=0.008). The predictive value of fractalkine did not significantly differ between patients with ischaemic and non-ischaemic HF aetiology (p=0.79). The predictive value of fractalkine tertiles was not significantly modified by tertiles of NT-proBNP (p=0.18) but was more pronounced in the first and third tertile of NT-proBNP. Fractalkine was also an independent predictor of cardiovascular mortality (p=0.015). Fractalkine levels were significantly lower in patients on angiotensin-converting enzyme inhibitor therapy (p<0.001). In conclusion, circulating fractalkine with its pro-inflammatory and immunomodulatory effects is an independent predictor of mortality in advanced HF patients. Fractalkine improves risk prediction beyond NT-proBNP and might therefore help to identify high risk patients who need special care. Our data indicate the implication of immune modulation in HF pathology.

Hepatocyte growth factor is a strong predictor of mortality in patients with advanced heart failure.

OBJECTIVE: To assess the prognostic value of the mitogenic, antiapoptotic, angiogenic and antifibrotic hepatocyte growth factor (HGF) in heart failure (HF). DESIGN: Prospective cohort study. SETTING/PATIENTS: Assessment of HGF levels at inclusion in 351 patients with advanced HF (median 75 years, interquartile range (IQR) 63-82, 66% male). MAIN OUTCOME MEASURES: All-cause mortality, cardiovascular mortality. RESULTS: During a median follow-up of 16 months, 26% of patients died. HGF tertiles were associated with an increasing risk for all-cause mortality (p < 0.001) with a hazard ratio (HR) of 3.06 (95% confidence interval (CI) 1.69 to 5.53) for the third compared with the first tertile. This association remained significant after multivariable adjustment for B-type natriuretic peptide (BNP) and other risk factors (p = 0.002). Subgroup analysis revealed that HGF was a strong predictor of the secondary end point cardiovascular mortality in ischaemic HF (p = 0.009) with an adjusted HR of 6.2 (95% CI 1.76 to 21.8) comparing the third with the first tertile but not in non-ischaemic HF (HR = 1.47, 95% CI 0.48 to 4.49, p = 0.5). Patients with high HGF but low BNP had a comparable survival rate to those with elevated BNP but low HGF (p=0.66). Of note, the dose of angiotensin converting enzyme (ACE) inhibitors inversely correlated with HGF concentrations (r = -0.25, p < 0.001). CONCLUSIONS: HGF is a strong and independent predictor of mortality in advanced HF and, in particular, in ischaemic HF. These results indicate that HGF with its multiple effects on myocardial function exerts an overall deleterious effect in advanced HF. HGF may be of special interest for risk prediction and tailoring of HF treatment.

Differences in the predictive value of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in advanced ischemic and non-ischemic heart failure.

OBJECTIVE: To assess the prognostic value of the pro-apoptotic, but also cell growth-inducing molecule soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) in heart failure (HF). METHODS: We assayed sTWEAK levels in 351 patients with advanced HF (non-ischemic: 130, ischemic: 221). During a median follow-up of 4.9 years, 195 patients (56%) died. RESULTS: sTWEAK concentrations were associated with extended survival in patients with non-ischemic (P=0.022), but not with ischemic HF (P=0.82). The inverse association in non-ischemic HF remained significant in a multivariable Cox regression model (P=0.025) with a hazard ratio of 0.40 (95% confidence interval: 0.21-0.77) comparing the third to the first tertile (P=0.007). CONCLUSION: Low sTWEAK levels independently predict mortality in advanced non-ischemic HF. sTWEAK-induced proliferation of cardiomyocytes may explain its impact on suvival. The different prognostic value of sTWEAK in ischemic and non-ischemic HF may point towards distinct pathogenic pathways determining the course of disease.

Prognostic value of pigment epithelium-derived factor in patients with advanced heart failure.

OBJECTIVE: Whereas angiogenesis, the formation of new blood vessels from preexisting vessels, may be beneficial in restoring failing myocardium, apoptosis may contribute to the progression of heart failure (HF). We investigated the role of pigment epithelium-derived factor (PEDF), a recently discovered antiangiogenic factor with additional proapoptotic effects, in patients with advanced HF. METHODS: We assayed PEDF levels in 351 patients with advanced HF at baseline. During the median follow-up time of 16 months, 50% of patients experienced the composite end point of rehospitalization and/or death. RESULTS: The risk of a clinical event increased with concentrations of the antiangiogenic marker PEDF, with a 1.94-fold higher risk in the third tertile compared with the first tertile (95% CI, 1.33-2.84). This association remained significant after adjustment for B-type natriuretic peptide (BNP) and other risk factors in a Cox regression model (P = .015). Experimental data revealed that PEDF may contribute to the progression of HF by inducing apoptosis in human cardiac myocytes and fibroblasts via activation of caspase 3. CONCLUSIONS: We suggest a role of PEDF in the progression of HF by inducing apoptosis of human cardiac myocytes and fibroblasts. Our clinical data suggest that PEDF concentrations may have the potential to become a valuable marker of the prognosis of HF, in addition to BNP.

Prognostic value of plasma midregional pro-adrenomedullin and C-terminal-pro-endothelin-1 in chronic heart failure outpatients.

AIMS: The identification of chronic heart failure (CHF) patients at high risk of adverse outcome remains a challenge. New peptides are emerging that may give additional information. In CHF patients, endothelin (ET) levels predict mortality risk. Adrenomedullin has been shown to predict mortality in ischaemic heart failure, but not in unselected or non-ischaemic CHF patients. Moreover, ADM and ET have never been assessed in one model. The aim of the present study was to assess the prognostic value of midregional-pro-adrenomedullin (MR-proADM) and C-terminal-pro-endothelin-1 (CT-proET-1) in outpatients with CHF. METHODS AND RESULTS: We measured plasma MR-proADM and CT-proET-1 levels in 786 consecutive CHF outpatients and compared them with B-type natriuretic peptide (BNP) levels. At 24-month follow-up, 233 patients had died. A stepwise forward Cox regression model with age, sex, estimated glomerular filtration rate, NYHA > II, left ventricular ejection fraction (LVEF), MR-proADM, CT-proET-1, and BNP as possible predictors revealed that MR-proADM levels [hazard ratio (HR) = 1.77, P < 0.001] in addition to age (HR = 1.02, P = 0.004), ejection fraction (HR = 0.98, P = 0.004), and NYHA > II (HR = 1.86, P < 0.001) were predictors of death at 24 months. When the analysis was repeated dependent on NYHA-stage, MR-proADM (HR = 2.12, P < 0.001) and LVEF (HR = 0.96, P = 0.006) were significant markers, but only in patients with mild/moderate CHF. CONCLUSION: Our data suggest that MR-proADM may be an important prognostic humoral marker, especially in mild/moderately symptomatic and non-ischaemic CHF patients.

Prognostic value of apoptosis markers in advanced heart failure patients.

AIMS: Apoptosis plays an important role in the progression of heart failure (HF). The purpose of this study was to assess whether the pro-apoptotic molecules apoptosis-stimulating fragment (FAS, CD95/APO-1) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) predict event-free survival of HF patients. METHODS AND RESULTS: We assayed soluble (s)FAS and sTRAIL levels in 351 patients with advanced HF. During the median follow-up time of 16 months, 175 patients (50%) experienced the composite endpoints: rehospitalization and death. The hazard increased with sFAS concentrations, with a hazard ratio of 2.3 comparing fourth and first quartiles. This association remained significant after adjustment for B-type natriuretic peptide (BNP) and other risk factors in a Cox regression model (P = 0.014). Patients with high sFAS but low BNP had a comparable event-free survival rate with those with elevated BNP only (P = 0.78). Conversely, high sTRAIL concentrations were related to a better prognosis. Particularly, the risk of mortality dropped by 70% in the fourth quartile of sTRAIL (P = 0.001, multivariable Cox regression model). CONCLUSION: sFAS is an independent risk predictor in advanced HF patients. It may be of particular value for the identification of high-risk patients in addition to BNP. Conversely, sTRAIL appears to be protective and could be an interesting therapeutic agent.

Chronic heart failure leads to an expanded plasma volume and pseudoanaemia, but does not lead to a reduction in the body's red cell volume.

Aims Chronic heart failure (CHF) is frequently associated with a decreased haemoglobin level, whereas the mechanism remains largely unknown. Methods and results One hundred consecutive CHF patients without anaemia or renal dysfunction based on non-cardiac reasons were enrolled. We explored determinants of anaemia (as iron parameters, erythropoietin, hepcidin and kidney function) including red cell volume (RCV) (by a 51 Cr assay) as well as related markers and plasma volume. The influence of each factor on haemoglobin concentrations was determined in a multiple regression model. Mean haemoglobin concentrations were 11.7 +/- 0.8 mg/dL in anaemic CHF patients and 14.4 +/- 1.2 mg/dL in non-anaemic patients. Corrected reticulocytes were lower in anaemic patients (35.1 +/- 15.7 vs. 50.3 +/- 19.2 G/L, P = 0.001), but the RCV was not reduced (1659.3 +/- 517.6 vs. 1826.4 +/- 641.3 mL, P = 0.194). We found that plasma volumes were significantly higher in anaemic CHF patients (70.0 +/- 2.4 vs. 65.0 +/- 4.0%, P < 0.001). Plasma volume was the best predictor of haemoglobin concentrations in the regression model applied (B = -0.651, P < 0.001, R(2) = 0.769). Conclusion Haemodilution appears to be the most potent factor for the development of low haemoglobin levels in patients with CHF. Our data support an additional independent, but minor influence of iron deficiency on haemoglobin concentrations in CHF patients.

Flow-mediated vasodilation predicts outcome in patients with chronic heart failure: comparison with B-type natriuretic peptide.

OBJECTIVES: The aim of this study was to assess the predictive potency of impaired endothelium-dependent flow-mediated vasodilation (FMD) in patients with chronic heart failure (CHF). BACKGROUND: Chronic heart failure is associated with reduced FMD; the prognostic impact of this observation is unknown. METHODS: Seventy-five ambulatory CHF patients (United Network of Organ Sharing [UNOS] status 2) with a left ventricular ejection fraction (LVEF) < or =30%, despite optimized medical therapy (angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, 100%; beta-blocker, 81%), were evaluated. Using high-resolution ultrasound, FMD of the brachial artery was assessed in addition to other neurohormonal, clinical, and hemodynamic variables. Age, gender, New York Heart Association (NYHA) functional class, LVEF, hemodynamic variables, B-type natriuretic peptide (BNP) levels, medical therapy, cardiovascular risk factors, and FMD were analyzed for prediction of the combined end point conversion to UNOS status 1 or death in a multivariate Cox model. RESULTS: Up to three years, 21 patients (28%) converted to UNOS status 1, and 6 patients (8%) died. Univariate risk factors for the combined end point were log BNP (p = 0.0032), FMD (p = 0.0033), NYHA functional class (p = 0.0132), beta-blocker therapy (p = 0.0367), and mean blood pressure (p = 0.0406). In the multivariate analysis, only FMD (p = 0.0007), log BNP (p = 0.0032), and mean blood pressure (p = 0.0475) were independently related to the combined end point. In the Kaplan-Meier plot, significantly more patients with FMD <6.8% (median) reached the combined end point, as compared with patients with FMD >6.8% (p = 0.004). CONCLUSIONS: In CHF, impaired FMD is a strong, independent predictor of conversion to UNOS status 1 or death.

Incidence of normal values of natriuretic peptides in patients with chronic heart failure and impact on survival: a direct comparison of N-terminal atrial natriuretic peptide, N-terminal brain natriuretic peptide and brain natriuretic peptide.

AIMS: N-ANP, N-BNP and BNP are proven to be excellent markers for diagnosis and the prediction of outcome in heart failure patients. Published studies on this subject differ in respect of their design and are therefore difficult to compare. The EuroHeart Failure Survey was undertaken to evaluate the drug prescription rate; the cohort of this survey best reflects clinical practice. The purpose of the present study was to compare the three hormones in clinical practice for the purpose of diagnosis and the prediction of outcome. Attention was focused on patients with normal values and the implications of these on survival. METHODS AND RESULTS: Of 341 patients recruited in the Austrian centers of the survey, blood samples for the determination of N-ANP, N-BNP and BNP were taken from 112 patients. Mortality within the observation period was defined as the endpoint. Normal levels of the hormones were found in 5% of cases for N-ANP, 25% for N-BNP and 30% for BNP. The mortality of patients with normal values was low (0%, 3% and 6%, respectively) and occurred late (after more than 23 months). Above-median levels of all three hormones resulted in a comparable mortality (51% survival for N-ANP, 50% for BNP and 49% for N-BNP). CONCLUSIONS: In a clinical setting, the risk stratification for outcome is similar for N-ANP, N-BNP and BNP. More importantly, all hormones are reliable parameters to diagnose CHF using normal values as a cut-point. However, N-ANP appears to be more sensitive than BNP or N-BNP.

Influence of age and in-patient care on prescription rate and long-term outcome in chronic heart failure: a data-based substudy of the EuroHeart Failure Survey.

AIMS: To evaluate the prescription rate of neurohumoral drugs in chronic heart failure patients and the factors influencing prescription rates. Outcomes and their predisposing factors were also investigated. METHODS AND RESULTS: Of 1482 consecutive patients admitted to 3 Austrian hospitals participating in the EuroHeart Failure Survey, 341 were included in this data-based substudy. Follow-up time to evaluate outcome was up to 46 months. The prescription rates of renin-angiotensin (RAAS) antagonists and beta-blockers at the time of discharge were evaluated. The overall prescription rate and dosage were lower than the recommended levels. Hospitals with cardiac care had a significantly higher prescription rate than those without (p<0.001). Patients older than 75 years received significantly less therapy (p<0.001) and a lower dosage of RAAS antagonists (p<0.01) than younger patients. Younger patients were treated more intensively in hospitals with cardiac care (p<0.05). Patients aged >75 years were under-treated, independent of the hospital (n.s.). Multivariate analysis showed that age was the most influencing factor on survival (chi(2) 15.5, p<0.0001). Additional influencing factors of long-term survival were type of the ward (chi(2) 7.9, p<0.005) and pharmacologic treatment (chi(2) 6.2, p<0.02). CONCLUSION: Patients with chronic heart failure are still under-treated in clinical practice. Younger patients benefit from hospitals with specialized cardiac care. Elderly patients are obviously under-treated compared with younger patients. Of several clinical parameters, age was the only independent variable predicting long-term survival.

Muscle strength as a predictor of long-term survival in severe congestive heart failure.

AIMS: The objective of the study was to test the relationship between isolated muscle strength and outcome, and its significance in the context of other exercise variables. METHODS AND RESULTS: 122 consecutive patients (LVEF 21+/-7%) were enrolled in the study. Isokinetic strength testing of the knee extensor and flexor muscles were performed. A subset of 51 patients underwent additional upright bicycle testing with gas exchange analysis. The outcome up to 60 months was defined by event-free survival (group A, n=59) or death (group B, n=34). Patients who had been transplanted were excluded from further analysis. The peak strength of the quadriceps muscle was comparable in both groups (N.S.). In contrast, the index (value adjusted for weight) did reveal significant differences (P<0.04), similar to the peak torque of the knee flexor muscle (P<0.04), whose index was even more significant with regard to differences (P<0.01). Multivariate analysis including muscle strength variables, pVO2 and workload into one model show that the flexor strength index is the only independent variable (x2=9 P<0.003). A cut-off point of 68 Nm x 100/kg in the strength index of the flexor muscles was used to establish a significant difference between groups with regard to outcome (P<0.01). Thus, the isokinetic strength of the knee flexor muscles is related to outcome. Moreover, this parameter is superior to variables such as peakVO2 and workload.

Dual rate-dependent cardiac electrophysiologic effects of haloperidol: slowing of intraventricular conduction and lengthening of repolarization.

Treatment with the neuroleptic agent haloperidol is sometimes associated with serious cardiac arrhythmias. The proarrhythmic potential of haloperidol may be linked to the drug's rate-dependent modulation of cardiac impulse conduction and repolarization. Herein these heart rate-dependent electrophysiologic actions of haloperidol are investigated in vivo. In anesthetized guinea pigs, haloperidol (0.02 mg/kg/min intravenously) produced significant rate-dependent slowing of intraventricular conduction. On abruptly changing the driving cycle length from 500 ms to 300 ms, conduction slowing rapidly reached a new steady state with a rate constant of 0.80 per beat +/- 0.07. The time course of recovery from conduction slowing on interruption of rapid pacing at a cycle length of 250 ms was well described by two time constants, tau(rec1) = 18.9 ms +/- 8.0 and tau(rec2) = 141.8 ms +/- 87.1, suggesting rapid dissociation of the drug from the Na+ channel. During prolonged stimulation, conduction slowing had a biphasic dependence on heart rate: for each 10-bpm increment in heart rate, conduction slowing increased by 7.9% at rates <220 bpm and by 17% at rates >220 bpm. At all tested cycle lengths, haloperidol caused a significant lengthening of Q(T) intervals, which was inversely dependent on heart rate. Numeric analysis suggested that the excessive increase in conduction slowing at rates >220 bpm was due to the drug's Q(T)-prolonging effect, indicating that, at short cycle lengths, the impulses encroached on the refractory period. Thus, in vivo, haloperidol slows intracardiac conduction with rapid on/off kinetics, comparable to the class I antiarrhythmic agent lidocaine. The Q(T) prolongation by haloperidol may lead to an excessive conduction slowing at high heart rates.