Prognosis In Chronic Heart Failure Research Articles

Abstract 2395: Treatment of Nocturnal Cheyne - Stokes - Respiration by Adaptive Servoventilation Improves Sleep Disordered Breathing and Cardiopulmonary Function in Patients with Chronic Heart Failure

Cheyne - Stokes respiration (CSR) is common in patients (pts) with chronic heart failure (CHF) and accompanied by an impaired prognosis. Nocturnal adaptive servoventilation (ASV) was recently introduced to treat CSR in CHF. Aim of this study was the investigation of long-term ASV effects on CSR and CHF parameters. In 41 pts with CHF treated according to current guidelines (39 male; 64.8 ± 10years, NYHA ≥ II, LV-EF ≤ 40%) cardiorespiratory polygraphy (PG), cardiopulmonary exercise (CPX) testing and echocardiography was performed before and after 11.6 ± 5.9 months (median 10.3 months) of ASV treatment (AutoSet CS ™ 2, ResMed). In our cohort, mean duration of ASV usage during night was 6:25 ± 1:08 h, while the device was used in 82 ± 21% of possible nights. Apnea-hypopnea-index and apnea-index were reduced from 38.2 ± 11/h to 5.5 ± 7/h and 24.2 ± 14/h to 2.5 ± 5/h, respectively (both p < 0.001). Minimum oxygen saturation rose from 81.4 ± 4.9% to 85.6 ± 4.3% (p < 0.001) while mean oxygen desaturation was reduced from 6.8 ± 2.5% to 4.6 ± 1.8% (p < 0.001). Peak oxygen consumption (VO 2 ) during CPX testing increased from 15.2 ± 3.7ml/kg/min to 17.1 ± 4.7ml/kg/min and predicted peak VO 2 from 60.1 ± 13% to 68.5 ± 18% (both p < 0.05). Left ventricular ejection fraction increased from 29.9 ± 6.6% to 33.3 ± 10.6% (p < 0.05). In selected and compliant pts with CHF and CSR, addition of nocturnal ASV therapy to standard heart failure therapy is able to abolish CSR and improve cardiac function. Whether this improvement in SDB and CHF parameters is accompanied with an improvement in CHF prognosis is not yet known.

Osteopontin—a novel biomarker of prognosis in chronic heart failure?

Osteopontin—a novel biomarker of prognosis in chronic heart failure?

Coenzyme Q10: An Independent Predictor of Mortality in Chronic Heart Failure

The aim of this study was to investigate the relationship between plasma coenzyme Q(10) (CoQ(10)) and survival in patients with chronic heart failure (CHF). Patients with CHF have low plasma concentrations of CoQ(10), an essential cofactor for mitochondrial electron transport and myocardial energy supply. Additionally, low plasma total cholesterol (TC) concentrations have been associated with higher mortality in heart failure. Plasma CoQ(10) is closely associated with low-density lipoprotein cholesterol (LDL-C), which might contribute to this association. Therefore we tested the hypothesis that plasma CoQ(10) is a predictor of total mortality in CHF and could explain this association. Plasma samples from 236 patients admitted to the hospital with CHF, with a median (range) duration of follow-up of 2.69 (0.12 to 5.75) years, were assayed for LDL-C, TC, and total CoQ(10). Median age at admission was 77 years. Median (range) CoQ(10) concentration was 0.68 (0.18 to 1.75) micromol/l. The optimal CoQ(10) concentration for prediction of mortality (established with receiver-operator characteristic [ROC] curves) was 0.73 micromol/l. Multivariable analysis allowing for effects of standard predictors of survival--including age at admission, gender, previous myocardial infarction, N-terminal peptide of B-type natriuretic peptide, and estimated glomerular filtration rate (modification of diet in renal disease)--indicated CoQ(10) was an independent predictor of survival, whether dichotomized at the ROC curve cut-point (hazard ratio [HR]: 2.0; 95% confidence interval [CI]: 1.2 to 3.3) or the median (HR: 1.6; 95% CI: 1.0 to 2.6). Plasma CoQ(10) concentration was an independent predictor of mortality in this cohort. The CoQ(10) deficiency might be detrimental to the long-term prognosis of CHF, and there is a rationale for controlled intervention studies with CoQ(10).

Weight loss and mortality risk in patients with chronic heart failure in the candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) programme

The curiosity that leanness is associated with poor survival in patients with chronic heart failure (CHF) needs further insight by investigating the impact of weight loss on prognosis in a large sample of patients across a broad spectrum of both reduced and preserved left ventricular (LV) systolic function. We investigated the change in weight over 6 months in 6933 patients in the Candesartan in Heart failure: Reduction in Mortality and morbidity (CHARM) programme, and its association with subsequent mortality (1435 deaths) over a median 32.9 months follow-up using Cox proportional hazard models to account for the impact of body mass index and other risk predictors. We then used time-updated Cox models to relate each patient's ongoing data on annual weight change to their mortality hazard. The percentage weight loss over 6 months had a highly significant monotonically increasing association with excess mortality, both for cardiovascular and for other causes of death. Patients with 5% or greater weight loss in 6 months had over a 50% increase in hazard compared with those with stable weight. Weight loss carried a particularly high risk in patients who were already lean at study entry. Findings were similar in the presence of dependent oedema, preserved or reduced LV ejection fraction, and treatment with candesartan, although weight loss was significantly less common on candesartan. The time-updated analyses revealed an even stronger link between weight loss and short-term risk of dying, i.e. risk increased more than four-fold for patients whose last recorded annual weight loss exceeded 10%. Weight gain had a more modestly increased short-term mortality risk. Weight loss accelerates in the year prior to death. Weight loss and leanness are important predictors of poor prognosis in CHF. Being lean and losing weight is particularly bad. The detection of weight change, and particularly weight loss, should be considered as an adverse sign prompting further evaluation.

Advanced Glycation Endproducts in Chronic Heart Failure

Advanced glycation endproducts (AGEs) have been proposed as factors involved in the development and progression of chronic heart failure (CHF). Cross-linking by AGEs results in vascular and myocardial stiffening, which are hallmarks in the pathogenesis of CHF. Additionally, stimulation of receptors by AGEs may affect endothelial function and myocardial calcium uptake and may perpetuate coronary sclerosis in CHF. CHF is common in conditions with AGE accumulation, such as diabetes and renal failure. This review describes in detail the interrelation of plasma AGEs, renal function, and the severity and prognosis in clinical CHF patients with mild to moderate loss of renal function. This association is compared with the relation between tissue AGE accumulation (marked by skin autofluorescence) and diastolic dysfunction in renal failure. The evidence reviewed here provides support for the assumed role of AGEs in determining the severity and prognosis of CHF, but also highlights the differences in this relation between plasma and tissue AGEs and between patients with and without advanced renal failure. Ongoing clinical intervention trials to reduce AGE accumulation in patients with CHF may elucidate the causal role of AGEs in the development and course of CHF.

The effect of the hemoglobin lever on the prognosis of chronic heart failure

目的 研究慢性心力衰竭(CHF)患者血红蛋白(Hb)水平对其预后的影响.方法 观察142例初次人院的CHF患者Hb与心功能的关系;并进行随访1年,对比在随访期间贫血组和非贫血组患者死亡、再住院次数、再住院总时间.结果 贫血发生率36.6%,心衰患者随着心功能恶化,Hb水平逐渐降低(P＜0.05),贫血发生率明显升高(P＜0.05);在随访期间,贫血组的死亡率比非贫血组提高了3倍,平均住院次数增加了近2倍,平均住院时问也增加了30%,贫血组和非贫血组患者相比,死亡率、平均住院次数和平均住院时间差异均有统计学意义(均P＜0.05).结论 贫血在CHF患者中常见,对CHF患者,Hb水平降低或贫血是预后不良因素之一。

Clinical and prognostic value of advanced glycation end-products in chronic heart failure

Advanced glycation end-products (AGEs) have been proposed as a novel factor involved in the development and progression of chronic heart failure (CHF). We aimed to determine whether plasma levels of N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL), two well-known AGEs, are related to the severity and prognosis of CHF. A total of 102 CHF patients, aged 58 +/- 12 years, with an average left ventricular ejection fraction of 28 +/- 9% were followed for 1.7 (1.2-1.9) years. NYHA functional class and NT-pro-BNP were used as estimates of the severity of CHF. CML and CEL were determined by LC-MS/MS. CML levels were associated with NYHA functional class (P < 0.001) and NT-pro-BNP levels (P < 0.001). Survival analysis for the combined end-point of death, heart transplantation, ischaemic cardiovascular event, and hospitalization for heart failure revealed that CML levels predicted outcome, even after adjustment for age, gender, aetiology of CHF, identified risk modifiers, and several known predictors of outcome in CHF. The predictive value of CML subsided after correction for renal function. CEL was not associated with the severity or prognosis of CHF. Plasma AGEs, in particular CML levels, are related to the severity and prognosis of CHF. The fact that the relation between CML and prognosis subsided after correction for renal function may suggest that AGE accumulation in renal failure explains part of the prognostic value of renal function in CHF. However, further investigation is warranted to exclude the possibility that CML is just an innocent marker of renal function.

Is uric acid itself a player or a bystander in the pathophysiology of chronic heart failure?

Uric acid (UA) is the end product of purine metabolism in humans. Hyperuricemia is often found in patients with chronic heart failure (CHF). The increase of serum UA level is inversely associated with disease severity, cardiac function and prognosis of CHF. Some researchers found that UA had detrimental impact on the cardiovascular system, including mediating immune response upon cell injury, increasing endotoxin-stimulated tumor necrosis factor-alpha production and hence proinflammatory immune activation, increasing blood pressure, and so on. Other researchers found that UA had important antioxidant properties by scavenging various reactive oxygen species. So far, there is no evidence suggest that UA has detrimental effect on the pathophysiology of CHF. Xanthine oxidase (XO) is an enzyme that produces uric acid during purine metabolism. XO activity is up-regulated in failing heart, and serum UA levels reflect the degree of XO activation in CHF. XO plays an important role in the pathophysiology process of CHF, including myocyte apoptosis, endothelial dysfunction and cardiac mechanoenergetic uncoupling. The therapeutic effect of long-term XO inhibition has been confirmed in animal models and partly in human bodies. We hypothesize that UA itself is not a player but a bystander associated with the activation of XO in the pathophysiology of CHF.

Only Large Changes (>80%) in BNP Modify Risk in Patients with Chronic Heart Failure

Introduction: B-type natriuretic peptide (BNP) has been used to estimate prognosis in chronic heart failure (HF) patients. Large biologic variability, however, potentially limits the usefulness of serial measurements. The magnitude of change in BNP levels necessary to be clinically meaningful remains to be established. Accordingly, we assessed changes (increases and/or decreases) in BNP during two years of follow-up to attempt to answer this question. Methods: A cohort of 172 ambulatory Class III-IV HF patients with complete serial (enrollment to event or last follow up) BNP data were studied from June 2001 to January 2004.

Cholesterol — A marker of nutritional status in mild to moderate heart failure

Objective To assess the association between serum cholesterol and nutritional status in patients with stable mild to moderate chronic heart failure (CHF). Background Hypercholesterolemia is a well-established risk factor for mortality and morbidity in coronary heart disease. In an apparent paradox, lower serum cholesterol has been associated with worse prognosis in CHF. Pre-albumin is the preferred marker for undernutrition in chronic diseases. Methods We evaluated 92 CHF patients, mean age 68 years, mean body mass index 27 kg/m 2; 44 with ischemic etiology; 41 in New York Heart Association class I. Patients were included after a period of at least 2 months of clinical stability. Spearman's correlation coefficient between serum cholesterol and pre-albumin, both in the whole sample and stratifying by the use of statins was calculated. Results Median (interquartile range) cholesterol level was 174 (142–214) mg/dl and median pre-albumin level was 31 (25–37) mg/dl. Overall, there was a moderately strong and statistically significant positive correlation between pre-albumin and serum cholesterol (Rho = 0.57, p < 0.001). Among the 20 patients not on statin the correlation coefficient was 0.84 ( p < 0.001), while among the 72 patients under a statin the correlation was 0.49 ( p < 0.001). Conclusion Our results suggest that in stable mild to moderate CHF patients, cholesterol levels are closely related with nutritional status irrespective of therapy with a statin.

94 The use of collagen-derived serum peptides in the prognosis of chronic heart failure

94 The use of collagen-derived serum peptides in the prognosis of chronic heart failure

Plasma Brain Natriuretic Peptide-Guided Therapy to Improve Outcome in Heart Failure: The STARS-BNP Multicenter Study

The aim of this multicenter study was to evaluate the prognostic impact of a therapeutic strategy using plasma brain natriuretic peptide (BNP) levels. The prognosis of chronic heart failure (CHF) remains poor, even among patients treated in specialized departments. A total of 220 New York Heart Association functional class II to III patients considered optimally treated with angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers, and diuretics by CHF specialists were randomized to medical treatment according to either current guidelines (clinical group) or a goal of decreasing BNP plasma levels <100 pg/ml (BNP group). Outpatient visits were scheduled every month for 3 months, then every 3 months. The primary combined end point was CHF-related death or hospital stay for CHF. Both groups were similar for baseline clinical and biological characteristics. Left ventricular ejection fraction was slightly lower in the BNP group than in the clinical group (29.9 +/- 7.7% vs. 31.8 +/- 8.4%, p = 0.05). At the end of the first 3 months, all types of drugs were changed more frequently in the BNP group. Mean dosages of ACEIs and beta-blockers were significantly higher in the BNP group (p < 0.05), whereas the mean increase in furosemide dosage was similar in both groups. During follow-up (median 15 months), significantly fewer patients reached the combined end point in the BNP group (24% vs. 52%, p < 0.001). In optimally treated CHF patients, a BNP-guided strategy reduced the risk of CHF-related death or hospital stay for CHF. The result was mainly obtained through an increase in ACEI and beta-blocker dosages.

A change in N‐terminal pro‐brain natriuretic peptide is predictive of outcome in patients with advanced heart failure

The prognosis of chronic heart failure has improved with modern medical therapy. However, identifying those patients who fail to respond to such therapy and therefore those who remain at high risk is notoriously difficult. The B-type natriuretic peptides are established independent predictors of prognosis in CHF. However, the relevance of a change in NT-proBNP concentration over time in advanced heart failure is unknown. We prospectively studied 133 patients with advanced CHF referred for consideration of cardiac transplantation. Plasma for NT-proBNP analysis was sampled at baseline and a median of 4 months later in the 112 patients surviving without cardiac transplantation. Patients were followed up for a median of 1003 days. The primary endpoint of all-cause mortality occurred in 30 (26.8%) patients. Those subjects who had the highest NT-proBNP concentration at 4 months were at the greatest risk of death (log rank statistic=10.4, p=0.001). On Cox regression analysis, both a NT-proBNP concentration above the median and an absolute increase in NT-proBNP were independent predictors of mortality (chi(2)=53, p<0.0001 and chi(2)=17.3, p<0.0001, respectively). A single NT-proBNP concentration above the median and a change in NT-proBNP concentration over a 4-month period were independent predictors of mortality in patients with advanced heart failure.

Central Sleep Apnea due to Chronic Heart Failure: Cheyne-Stokes Respiration

There is increasing evidence that sleep-disordered breathing may contribute to the progression and prognosis of chronic heart failure (CHF). The presence of sleep-disordered breathing, especially central sleep apnea syndrome (CSAS), commonly referred to as Cheyne-Stokes respiration, may be a potent predictor of adverse prognosis in patients with CHF. CSAS is estimated to be present in 25% to 50% of patients with CHF and is related to the severity of CHF, exercise tolerance (VE/VCO2 slope), and neurohormoral derangements. We performed a multicenter randomized, controlled trial to clarify the effects of nocturnal home oxygen therapy (HOT) in patients with CSAS due to CHF (New York Heart Association class II or III, left ventricular ejection fraction 5 dips/hour). The CHF-HOT study demonstrated significant improvements in the apnea-hypopnea index, left ventricular ejection fraction, and the specific activity scale following 12 weeks of nocturnal HOT. The subanalysis revealed significant reductions in the frequencies of hospitalization (2.1 to 0.5 times/year), emergency visits (2.5 to 0.7 times/year) as compared with those before the introduction of nocturnal HOT. The pathophysiology of CSAS is being clarified, and novel treatments should be developed.

Novel and potential future biomarkers for assessment of the severity and prognosis of chronic heart failure

Novel and potential future biomarkers for assessment of the severity and prognosis of chronic heart failure

Beta-blockade in CHF: pathophysiological considerations

Sympathetic activation leading to raised levels of catecholamines is one of the earliest responses to the fall in cardiac output that occurs in chronic heart failure (CHF). Raised catecholamine levels have numerous adverse effects that can be counteracted by beta-blockers. For example, the increased heart rate associated with sympathetic activation is associated with a poor prognosis in CHF. In the major beta-blocker trials in CHF a reduction in mortality of about 35% was consistently demonstrated with beta-blockade, which was associated with a reduction in heart rate of 10-15 bpm. The resting heart rate predicts longevity in many mammalian species. A limited ability to increase heart rate during exercise (chronotropic incompetence) in left ventricular (LV) dysfunction and CHF also predicts mortality. Beta-blockers increase heart rate variability by rebalancing the sympatho-vagal axis. Beta-blockers also reduce remodelling in CHF, increase LV ejection fraction, reduce end-systolic volume, and improve ventricular filling time. They are also believed to have a direct anti-arrhythmic action that protects against sudden cardiac death and to have additional effects at the cellular level on myocyte hypertrophy and apoptosis.

Neurohormones and inflammatory mediators in patients with heart failure undergoing cardiac resynchronization therapy: Time courses and prediction of response

Despite interest in neurohormonal activation as a determinant of prognosis in chronic heart failure (CHF) and as a target for pharmacological treatments, data are lacking on the time-related effects of electrical cardiac resynchronization therapy (CRT) on a broad spectrum of neurohormones and cytokines. The aim of this study was to assess time-courses and extents of changes within the neurohormonal profile of CHF patients treated with CRT. We performed a prospective follow-up study in 32 patients with NYHA class III–IV CHF to investigate the effects of CRT on a broad panel of neurohormones proposed for characterization of CHF patients. Levels of atrial and brain natriuretic peptides (ANP, BNP), epinephrine, norepinephrine, aldosterone, plasma renin activity, IL-6, TNF, soluble receptors sTNFR1 and 2, and chromogranin A were assessed before implantation and after 3 months of CRT; when feasible, measurements were also performed at 1 week, 1 month and 12 months (clinical evaluation, echocardiography and ECG were also performed at each time-point). The results showed that at 3 months improvement in NYHA class and echographically assessed left ventricular (LV) reverse structural remodeling were accompanied by significant reductions versus baseline in ANP and BNP, but not in other neurohormones. Moreover a baseline ANP concentration ≤150 pg/ml was a good predictor of response to CRT in terms of NYHA class reduction and reverse LV remodeling. In conclusion 3 months of CRT significantly reduce natriuretic peptides concentrations, while values of other neurohormones and inflammatory cytokines are relatively unvaried. A baseline ANP concentration ≤150 pg/ml might be a clinically useful predictor of medium-term response to CRT.

The value of cardiopulmonary exercise testing and brain natriuretic peptide plasma levels in predicting the prognosis of patients with chronic heart failure

Background A peak VO 2 above 14 ml/min/kg at cardiopulmonary exercise testing and brain natriuretic peptide (BNP) levels is used to estimate survival in patients with chronic heart failure (CHF). Limited data, however, exist comparing the prognostic value of both markers simultaneously in patients with mild to moderate CHF. Methods We prospectively studied 85 consecutive patients (59 ± 13 years, 63 men) with CHF (mean LVEF 26 ± 6%). All patients underwent cardiopulmonary exercise testing with determination of peak VO 2 and measurement of plasma BNP at rest. The incidence of cardiac decompensation and cardiac death was recorded in the follow-up. Results During a mean follow-up of 427 ± 150 days, four deaths and ten cardiac decompensations occurred. Kaplan–Meier estimates of freedom from clinical events differed significantly for patients above and below the median BNP of 292 pg/ml and also for patients above and below a peak VO 2 of 14 ml/min/kg ( p < 0.05 each). BNP and peak VO 2 (area under the ROC 0.75 vs. 0.72) showed a comparable discrimination of CHF patients with adverse cardiac events. The prognostic information of BNP was at least as powerful as that derived from peak VO 2. A BNP above 324 pg/ml was associated with a risk ratio of 8.8 for adverse cardiac events. Conclusions In patients with mild to moderate CHF, BNP measurements appear to be an alternative to peak VO 2 determined by cardiopulmonary exercise testing for the assessment of prognosis in CHF. BNP may facilitate the ambulatory management of patients with mild to moderate CHF since it is less expensive, less time-consuming, and free of procedural risk compared to exercise testing.

“CYTOKINE” MODEL OF PATHOGENESIS OF CHRONIC HEART FAILURE AND THE OPPORTUNITIES OF NEW THERAPEUTIC STRATEGY IN DECOMPENSATED PATIENTS

Neurohumoral model of pathogenesis of chronic heart failure (CHF) made it possible to develop new therapeutic approaches in patients with CHF . However , it became obvious that the ways of activation of neurohumoral systems in CHF are much more complicated. The increase in local synthesis of hormones causes the activation of inflammatory cytokines and protooncogenes, which have various negative effects. This allowed formulating immunoinflammatory conception of CHF pathogenesis, according to which the increase in interleukine-6 blood level is the marker of unfavorable prognosis for CHF , and the level of tumor necrosis factor-α (TNF-α) straightly correlates with severity of clinical condition and neurohumoral activity in CHF . The growth of TNF-α in CHF progressing as well as its reduction in successful treatment do not exclude the probability of positive effect of therapy , focused on the reduction of TNF-α concentration. The pathogenesis peculiarities of CHF including cytokine aggression demand the necessity of development of new therapy approaches with the use of cytokine system modulators.

Big endothelin-1 is not a predictor in aortic stenosis, but is related to arterial blood pressure

Background In aortic stenosis, natriuretic peptides have recently been shown to correlate with ventricular function and to predict symptom-free survival and outcome. Elevated big endothelin-1 (bigET) is associated with poor prognosis in chronic heart failure, but little is known about its role in severe aortic stenosis. Methods In 61 patients with aortic stenosis (71 ± 10 years, mean gradient 65 ± 20 mm Hg, valve area 0.63 ± 0.15 cm 2), plasma bigET was determined by radioimmunoassay and related to echocardiographic parameters, symptoms and survival. Patients were followed for 1 year. Results BigET (mean 2.3 ± 1.5, range 0.1–7.5 fmol/ml) was elevated ≥ 1.9 fmol/ml in 54% of patients, but was not correlated to the transvalvular gradients or valve area. BigET did not differ significantly between 14 asymptomatic (2.4 ± 1.0 fmol/ml) and 47 symptomatic patients (2.3 ± 1.6 fmol/ml), although the highest levels were observed in 5 patients in NYHA class III–IV (4.2 ± 2.2 fmol/ml, p = 0.035). No significant difference in bigET was observed between 51 survivors and 10 patients who died during follow-up (2.2 ± 1.4 vs 2.7 ± 1.6 fmol/ml). BigET did not differ between 7 asymptomatic patients developing symptoms and those remaining asymptomatic during follow-up. BigET was significantly related to the systolic blood pressure and left ventricular systolic pressure ( r = 0.389, p = 0.0025 and r = 0.401, p = 0.0018, respectively), but not to the diastolic blood pressure or interventricular septal wall thickness. BigET was inversely related to the left ventricular ejection fraction ( r = 0.327, p = 0.01) and fractional shortening ( r = 0.391, p = 0.044). Conclusion Although frequently elevated, bigET-1 is not a useful predictor of symptoms or outcome in patients with severe aortic stenosis. BigET increases inversely with left ventricular function and directly with systolic left ventricular and blood pressure, but is not related to transvalvular gradients or valve area.