Predictors of prognosis in patients with stable mild to moderate heart failure

BACKGROUND: A number of prognostic indexes have been developed to predict the outcome of patients with severe heart failure (HF). In patients with mild to moderate HF, however, there is no consensus regarding the usefulness of such indexes. The goal of this study is to determine the prognostic value of selected clinical variables in the latter group of patients. METHODS AND RESULTS: We prospectively evaluated the prognostic value of the functional capacity evaluation, the ventricular function, biochemical metabolic indicators, and brain natriuretic peptide (BNP) levels in 139 consecutive patients with mild to moderate HF. A clinical and echocardiographic examination (M-mode, 2D and pulsed Doppler of the mitral inflow); a 6-minute walk test; and a determination of serum sodium, uric acid, and BNP levels were performed. Death by any cause was predefined as the study end-point. Variables found to be related with survival in a univariate Cox regression analysis were NYHA class; ischemic origin for HF; left ventricular ejection fraction; deceleration time of the E wave; and 6-minute walk distance, serum sodium, uric acid, and BNP levels. In a multivariate analysis, ischemic origin of HF, 6-minute walk distance, deceleration time of the E wave, and BNP levels were found to be independent prognostic factors. The clustering of the independent prognostic factors was associated with the worse prognosis. CONCLUSIONS: These results suggest that the noninvasive evaluation used in this study and in our population of patients with mild to moderate HF allows the identification of individuals with the worst prognosis. The selected variables might prove to be very helpful in stratifying HF patients and identifying those that might benefit the most from a HF management program.     

Baroreflex sensitivity and cardiovascular mortality in patients with mild to moderate heart failure.

OBJECTIVE--To assess the influence of both sympathetic (plasma noradrenaline concentrations) and parasympathetic (baroreflex activation) tone on survival in patients with congestive heart failure. DESIGN--Invasive study with determination of parasympathetic activity and follow up for at least 4.5 years. SUBJECTS--35 patients with sinus rhythm and mild to moderate heart failure (New York Heart Association grades II-III) (mean age 53 (SD 3)). RESULTS--20 patients whose hearts survived were compared with 15 patients whose hearts did not (12 died and three received transplants). The two groups differed significantly in terms of mean arterial blood pressure (98 (3) v 90 (3) mm Hg), heart rate (82 (2) v 93 (4) beats/min), and mean pulmonary artery pressure (24 (3) v 35 (2) mm Hg) (all P < 0.05), while cardiac index, stroke volume index, and right atrial pressures were not different. The survivors had significantly lower plasma renin activities (3.6 (0.8) v 9.0 (3.6) angiotensin I/ml/h; P < 0.05) and tended to have lower noradrenaline values than non-survivors (170 (23) v 286 (74) pg/ml) at baseline. Baroreflex sensitivity was significantly lower in non- survivors than in survivors (1.3 (0.2) v 2.3 (0.3) ms/mm/Hg); P < 0.02). As the time of cardiac transplantation is dependent on complex logistical factors the three patients who received a transplant were excluded from the analysis of survival time. The risk of death in relation to baroreflex sensitivity at the median sensitivity of 1.48 ms/mm Hg was calculated. Survival was significantly different (P < 0.04) between the resulting two groups; three of the 16 subjects with high baroreflex sensitivity died compared with nine of the 16 with a baroreflex sensitivity < 1.48 ms/mm Hg. When systemic blood pressure, pulmonary artery pressure, stroke volume index, plasma noradrenaline concentrations, and baroreflex sensitivity were entered into a Cox proportional hazards regression, only systolic blood pressure and plasma noradrenaline values predicted survival (P < 0.001). CONCLUSIONS--Low vagal tone is correlated with a poor prognosis in patients with heart failure. Sympathetic tone measured as plasma noradrenaline concentration also contributed to survival. An additional contribution of vagal tone to survival could not be shown when sympathetic tone was considered simultaneously. This may be due to the inverse relation of sympathetic and parasympathetic tone and to the insensitivity of the multiple regression method to identify additional risk factors in small numbers of patients.     

Placebo controlled trial of felodipine in patients with mild to moderate heart failure. UK Study Group.

OBJECTIVE--To compare the effects of felodipine and placebo in patients with New York Heart Association functional class II or III and stable congestive heart failure despite treatment with an angiotensin converting enzyme inhibitor, diuretic, or digoxin, or any combination of these three drugs. PATIENTS AND DESIGN--252 patients were randomised in a double blind, parallel group study after a 2-4 week placebo run-in to oral treatment with either felodipine extended release formulation or placebo 2.5-10 mg twice daily given in addition to existing background medication for a further 12 weeks. METHODS--Patients aged 18-75 years of either sex with chronic congestive heart failure due to ischaemic heart disease, hypertensive heart disease, or dilated cardiomyopathy with or without secondary mitral insufficiency that was stable during the preceding two months were included in the study. Treadmill exercise tests according to the modified Naughton protocol were performed at baseline, and after six, 11, and 12 weeks of treatment. Signs and symptoms of heart failure were assessed at every visit. Physical examination was performed and left ventricular ejection fraction measured at baseline and after 12 weeks. RESULTS--Mean (SD) baseline exercise test times increased from 434 (162) s and 480 (157) s for felodipine and placebo groups respectively to 541 (217) s and 591 (218) s at 12 weeks or the last visit. The change in exercise from baseline to last visit was 107 (141) s for patients given felodipine and 112 (128) s for those given placebo (P > 0.20). There was also no difference between treatments with respect to the other efficacy variables. There were few deaths in the study (felodipine n = 3, placebo n = 2). More patients who received felodipine were withdrawn from treatment (n = 29) than those who received placebo (n = 17). The most common adverse events of the 54 and 28 cited as reasons for withdrawal in the felodipine and placebo groups respectively were increased need for non-study heart failure treatment (n = 10; 8%)--that is, starting new medication or changes in the dosage of existing treatment for patients given felodipine, and nausea (n = 4; 3%) for those given placebo. Patients withdrawn from the study due to increased need for non-study heart failure treatment rapidly stabilised and recovered. CONCLUSION--Felodipine has not been shown to be of benefit in patients with mild to moderate heart failure.     

Gender differences in mortality after acute myocardial infarction with mild to moderate heart failure

BACKGROUND: Heart failure (HF) is associated with poor outcome after acute myocardial infarction (AMI). Women have higher mortality rate than men after AMI, however, it is unknown whether women with HF after AMI have different prognosis than men. AIM: To compare the prognosis of men and women with AMI and mild-moderate HF. METHODS: We analyzed data of 3456 consecutive patients with AMI hospitalized in all cardiac care units in Israel during two nationwide surveys. RESULTS: Among patients with AMI and HF on admission: women were older, had more risk factors, and were less likely to undergo percutaneous coronary angiography/intervention. Women with HF had higher (7-days, 30-days, and 1-year) crude mortality rates than men. However, adjusted mortality rates were not significantly different between genders. CONCLUSIONS: Women with AMI complicated by HF had higher crude mortality rate than men that was eliminated after multivariate analysis, suggesting that the higher mortality rate may be attributed to increased prevalence of risk factors and lower rate of revascularization and medical therapies among women. Women with AMI and HF should be considered as a high-risk subgroup with adverse outcome. It remains to be determined whether more intensive management will improve their prognosis.     

Comparison of captopril and ibopamine in mild to moderate heart failure.

OBJECTIVE: To determine the effects of ibopamine 100 mg three times daily compared with captopril 25 mg three times daily on exercise capacity in patients with chronic heart failure. DESIGN: A randomised, double blind, parallel group comparison of the addition of ibopamine versus captopril during a period of 24 weeks. SETTING: 26 outpatient cardiology clinics in seven European countries. PATIENTS: 266 patients, with mild to moderate chronic heart failure (New York Heart Association (NYHA) functional class II, 81% and III, 19%) and evidence of an enlarged left ventricle. Patients received concomitant treatment with diuretics and/or digitalis. MAIN OUTCOME MEASURE: Exercise duration after 24 weeks of treatment, compared with baseline. RESULTS: Mean (SD) ejection fraction was 29 (8)% and the baseline exercise duration in the captopril and ibopamine groups 665 (160) and 675 (174) seconds, respectively. At the end of the study, exercise duration had improved in both groups, by 29 seconds in the ibopamine group (P < 0.01), and by 24 seconds in the captopril group (P < 0.05). There was no difference between groups (P = 0.69, 95% confidence interval -22 to 33). NYHA class, signs and symptoms score, and dyspnoea and fatigue index improved equally in both groups. The total number of adverse events was the same in both treatment groups, but gastrointestinal complaints occurred more often in the ibopamine group. The number of patients with premature withdrawals was no different. CONCLUSIONS: No difference was detected between the effect of captopril and ibopamine on exercise time in patients with mild to moderate heart failure during a treatment period of 24 weeks.     

Obesity,heart failure and sudden death

AIM: To review the direct unfavourable effect of obesity, the most prevalent nutritional and metabolic disease worldwide, on cardiovascular morbidity and mortality. DATA SYNTHESIS: Obesity is associated with high chronic cardiac workload due to the need to supply more blood to peripheral tissue. The high cardiac output is mainly a consequence of the greater requirements of increased lean body mass, and is maintained by an increased stroke volume and high normal heart rate, and sustained by an increase in ventricular mass. The increase in left ventricular (LV) mass also implies an increase in non-muscular tissue that plays a role in the development of electrical abnormalities, heart failure and sudden death. CONCLUSIONS: Obesity per se is a major risk factor for heart failure. Obesity-related LV hypertrophy is in turn associated with varying degrees of systolic and diastolic dysfunction that are not easily recognisable using traditional methods, but are potentially reversible after appropriate, stable moderate weight loss.     

心力衰竭猝死的防治

心力衰竭是一种终末期心脏疾病。随着人群年龄增高及心肌梗死等其他心脏疾病的成功救治,心力衰竭的患病率显著上升,我国心力衰竭患病率为0.9%。心力衰竭是心脏性猝死(sudden cardiac death,SCD)的常见病因。心脏性猝死发病机制复杂,但大部分由室性心动过速、心室颤动等恶性心律失常引起。因此预防恶性心律失常的发生,及时终止室性心动过速或心室颤动是防治心脏性猝死发生的关键。     

Risk of sudden death in heart failure patients

Sudden death is one of the more important cause of mortality in patients with chronic heart failure. The highest risk occurs among patients with less severe functional impairment, whereas patients in NYHA class IV usually die of progression of heart failure. Predictors of sudden death have been evaluated. Nevertheless, current methods of risk stratification for sudden death are still inadequate, especially in patients with advanced heart failure. Low left ventricular ejection fraction is widely used for the risk stratification, but it lacks of sensitivity and specificity in distinguishing patients with an increased arrhythmic mortality from those with an increased mortality due to pump failure. Unsustained ventricular tachycardia and inducibility at electrophysiological study may help identifying high-risk patients, requiring more aggressive therapy, as the ICD implantation. Heart rate variability and baroreflex sensitivity analysis have been utilized to obtain information on autonomic modulation, but with uncertain conclusion on the identification of high-risk patients. Increased QT dispersion, the presence of T-wave alternans and abnormal signal-averaged electrocardiography have also been proposed, but, up-to-now, any of these parameters showed a strong predictor power. In conclusion, our capability to identifying heart failure patients at risk for arrhythmic death is still far from being satisfactory.     

Risk stratification for sudden death in heart failure

Clinical trials provide evidence that an empiric approach of implantable cardioverter-defibrillator (ICD) implantation in heart failure patients (ejection fraction =/< 35%) with mild to moderate symptoms reduces mortality rate as compared to the best available medical therapy. However, ejection fraction alone is unable to predict death by progressive pump failure or sudden arrhythmic death, and consequently over half of all patients will not require device therapy over long-term follow-up. Thus, the approach of empiric ICD implantation results in excessive cost in the absence of more specific risk stratification for sudden death. This review summarizes the current noninvasive risk stratifying strategies available in predicting susceptibility to sudden arrhythmic death in heart failure populations.     

Acute and chronic hemodynamic effects of xamoterol in mild to moderate congestive heart failure.

Xamoterol, a new beta 1 partial agonist, has the potential to modulate cardiac response to variations in sympathetic tone in patients with heart failure. Its properties should result in beta-receptor stimulatory effects at low levels of sympathetic tone and beta-receptor protective effects at higher levels of sympathetic tone. The acute effects of intravenous (i.v.) xamoterol on hemodynamics at rest and during exercise were studied in 30 patients with mild to moderate heart failure (13 patients in New York Heart Association class II; 17 in class III) due to ischemic (n = 24) or cardiomyopathic (n = 6) heart disease. Cardiac index, stroke volume and stroke work index at rest were significantly improved after i.v. administration of xamoterol and consistent with net agonist effects. During exercise, heart rate and double product were significantly reduced (net antagonist effects), but with preservation of the expected increases in cardiac index and systolic blood pressure. These hemodynamic findings confirm the ability of xamoterol to modulate cardiac response to variations in sympathetic tone. Tachyphylaxis and arrhythmogenicity limit the chronic use of drugs with full beta-agonist properties as positive inotropes in heart failure. The patients were therefore entered into a 6-month double-blind, placebo-controlled, crossover study of chronic oral xamoterol therapy, 200 mg twice daily, and the hemodynamic responses to i.v. xamoterol were repeated at the end of the trial. No impairment in either resting or exercise effects was observed, indicative of a maintained response and absence of tachyphylaxis after chronic therapy. Furthermore, 24-hour ambulatory electrocardiographic monitoring showed no change in ventricular arrhythmias during oral treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genomics,heart failure and sudden cardiac death

Sudden cardiac death (SCD) is among the most common causes of death in developed countries throughout the world. Despite decreased overall cardiac mortality, SCD rates appear to be increasing in concert with escalating global prevalence of coronary disease and heart failure, the two major conditions predisposing to SCD. This unfavorable trend is a consequence of our inability to identify those who will die suddenly from lethal ventricular arrhythmias and to develop effective therapies for all populations at risk. The known risk factors for SCD lack the predictive power needed to generate preventive strategies for the large number of fatal arrhythmic events that occur among lower-risk subsets of the population. Even among recognized high-risk subsets, prediction of SCD remains challenging. With the exception of the implantable cardioverter defibrillator (ICD) there are few effective strategies for the prevention and treatment of SCD. This article discusses the prospect of genomic science as an approach to the identification of patients at high-risk for SCD. While the final common pathway for SCD is malignant ventricular arrhythmias, there are many potential contributors, pathways, and mechanisms by which common genetic variants (polymorphisms) could affect initiation and propagation of life-threatening cardiac arrhythmias. Recent advances in genomic medicine now provide us with novel approaches to both identify candidate genes/pathways and relatively common polymorphisms which may predispose patients to increased risk for SCD. Improved understanding of the relationship between common polymorphisms and SCD will not only improve risk stratification such that ICDs can be targeted to those patients most likely to benefit from them but also provide new insight into the pathophysiology of SCD.     

Usefulness of spatial dispersion of QRS duration in predicting mortality in patients with mild to moderate chronic heart failure

To prospectively evaluate the prognostic significance of spatial dispersion of QRS duration (S-QRSd) on a signal-averaged electrocardiogram in patients with chronic heart failure (CHF), we studied 114 consecutive stable outpatients with radionuclide left ventricular ejection fraction <40%. Cardiac and sudden deaths were significantly more often observed in patients with than without abnormal S-QRSd. S-QRSd is a powerful prognostic marker of the mortality in patients with mild to moderate CHF.     

Predictors of mortality and morbidity in patients with chronic heart failure.

AIMS: We aimed to develop prognostic models for patients with chronic heart failure (CHF). METHODS AND RESULTS: We evaluated data from 7599 patients in the CHARM programme with CHF with and without left ventricular systolic dysfunction. Multi-variable Cox regression models were developed using baseline candidate variables to predict all-cause mortality (n=1831 deaths) and the composite of cardiovascular (CV) death and heart failure (HF) hospitalization (n=2460 patients with events). Final models included 21 predictor variables for CV death/HF hospitalization and for death. The three most powerful predictors were older age (beginning >60 years), diabetes, and lower left ventricular ejection fraction (EF) (beginning <45%). Other independent predictors that increased risk included higher NYHA class, cardiomegaly, prior HF hospitalization, male sex, lower body mass index, and lower diastolic blood pressure. The model accurately stratified actual 2-year mortality from 2.5 to 44% for the lowest to highest deciles of predicted risk. CONCLUSION: In a large contemporary CHF population, including patients with preserved and decreased left ventricular systolic function, routine clinical variables can discriminate risk regardless of EF. Diabetes was found to be a surprisingly strong independent predictor. These models can stratify risk and help define how patient characteristics relate to clinical course.